Journal articles on the topic 'HLA-DQB1*06:02'
To see the other types of publications on this topic, follow the link: HLA-DQB1*06:02.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'HLA-DQB1*06:02.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Lorenzoni, Paulo José, Lineu Cesar Werneck, Ana Christina de Souza Crippa, Alessandra Zanatta, Cláudia S. Kamoi Kay, Carlos Eduardo S. Silvado, and Rosana Herminia Scola. "Is there a relationship between narcolepsy, multiple sclerosis and HLA-DQB1*06:02?" Arquivos de Neuro-Psiquiatria 75, no. 6 (June 2017): 345–48. http://dx.doi.org/10.1590/0004-282x20170063.
Full textAbstract:
ABSTRACT We studied multiple sclerosis (MS) patients with the HLA-DQB1*06:02 allele and compared them with MS patients who did not carry the HLA-DQB1*06:02 allele. We analyzed clinical and neurophysiological criteria for narcolepsy in six MS patients with HLA-DQB1*06:02, compared with 12 MS patients who were HLA-DQB1*06:02 non-carriers. Only two patients with HLA-DQB1*06:02 allele scored higher than 10 on the Epworth Sleepiness Scale. Polysomnography recording parameters and the multiple sleep latency test showed an absence of narcolepsy in the study group. Our study suggested no significant correlation between narcolepsy, MS and HLA-DQB1*06:02. The HLA-DQB1*06:02 allele alone was not sufficient to cause MS patients to develop narcolepsy.
2
Sophia Hsuan-Jung, Chen, Miyadera Hiroko, and Tokunaga Katsushi. "Analysis of HLA-DQ protein and peptide interaction in association to auto-immune mechanism of narcolepsy. (P5069)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 111.17. http://dx.doi.org/10.4049/jimmunol.190.supp.111.17.
Full textAbstract:
Abstract Human narcolepsy is a sleep disorder characterized by excessive daytime sleepiness (EDS), cataplexy, and abnormalities of rapid eye movement (REM). Strong HLA class II association was determined where the narcoleptic individuals of diverse ethnic backgrounds share a specific HLA class II haplotype, DQA1*01:02-DQB1*06:02. It has been also reported that hypocretin in the CSF of narcoleptic patients are significantly decreased and that hypocretin producing cells are disrupted in patients’ brain. We hypothesized that hypocretin or other proteins specifically expressed in hypocretin producing cells in the hypothalamus, are presented by HLA-DQA1*01:02-DQB1*06:02, and induce activation of self-reactive T cells. To analyze the peptide-binding reperitore of HLA-DQA1*01:02-DQB1*06:02, we transduced murine fibroblast cells with HLA-DQA1*01:02-DQB1*06:02 (suscceptible), DQA1*01:03-DQB1*06:01 (resistant), DQA1*01:03-DQB1*06:03 (resistant), and DQA1*01:02-DQB1*06:04 (neutral) alleles by retrovirus-vectors and confirmed stable DQ proteins expression. Using these cell lysates we analyzed binding affinity of synthetic peptides designed for hypocretin-A, -B, and other proteins expressed in hypocretin producing cells.
3
Loginova, M. A., S. S. Kutyavina, D. N. Smirnova, V. V. Cheranev, and I. V. Paramonov. "FEATURES OF DISTRIBUTION HLA-ALLELES AND HAPLOTYPES IN KALMYKS." Russian Clinical Laboratory Diagnostics 64, no. 4 (October 7, 2019): 243–49. http://dx.doi.org/10.18821/0869-2084-2019-64-4-243-249.
Full textAbstract:
Conducted high-resolution HLA-typing loci HLA-A, -B, -C, -DRB1 and -DQB1 by massively parallel sequencing of 150 potential donors of hematopoietic stem cells from the Republic of Kalmykia. In the studied population, four new alleles identified that not previously registered by the International Committee on the Nomenclature of Factors of the HLA-system of WHO. During the HLA-typing identified: 29 alleles at the HLA-A locus, 44 - at the HLA-B locus, 26 - at the HLA-C locus, 15 - at the DQB1 locus, 37 - at the HLA-DRB1 locus. The following alleles have a frequency of more than 10%: HLA-A*02:01 (11,7%), HLA-A*01:01 (11%), HLA-B*51:01 (10,3%), HLA-B*58:01 (10,3%), HLA-C*06:02 (17,7%), HLA-C*03:04 (10,3%), HLA-C*03:02 (10%), HLA-DQB1*03:01 (26,7%), HLA-DQB1*02:02 (10%), HLA-DRB1*07:01 (11,7%). The most common HLA-A-B-C-DQB1-DRB1 haplotype is A*02:05-B*50:01-C*06:02-DQB1*02:02-DRB1*07:01 (3,7%). Deviations from the Hardy - Weinberg equilibrium not identified.
4
Bubnova, L. N., E. V. Kuzmich, I. E. Pavlova, E. V. Belyaeva, and M. A. Terentyeva. "Comparative analysis of immunogenetic characteristics of potential hematopoietic stem cell donors from the registries of two Russian megapolises." Medical Immunology (Russia) 24, no. 5 (October 31, 2022): 1047–56. http://dx.doi.org/10.15789/1563-0625-cao-2539.
Full textAbstract:
Efficacy of search for the unrelated compatible transplant donors depends on a number of factors. Of most importance are the standards of primary HLA typing, and the immunogenetic diversity of the donor pool. Timely donor selection guarantees the optimal timing for stem cell transplantation. This factor exerts positive influence upon the transplantation outcomes. In 2019, The Bone Marrow Donors Registry at the Russian Research Institute of Haematology and Transfusiology has implemented HLA-typing for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 genes as a standard for primary immunogenetic examination, in order to reduce the donor search period. The aim of our study was to evaluate the HLA typing results for potential stem cell donors at our Registry as compared with immunogenetic profile of donors at the Registries arranged in two Russian megapolises. All currently known groups of HLA-C, HLA-DRB1, HLA-DQB1 gene alleles, 19 of 21 open groups of HLA-A gene alleles, 34 of 36 known groups of HLA-B gene alleles were screened in the donors from our Registry. The most common HLA alleles groups were as follows: A*02 (0.2957), A*03 (0.1432), A*01 (0.1155), A*24 (0.1128); B*07 (0.1282), B*35 (0.1084), B*44 (0.0921), B*18 (0.0745); C*07 (0.2738), C*04 (0.1361), C*12 (0.1202), C*03 (0.1134), C*06 (0.1127); DRB1*15 (0.1445), DRB1*07 (0.1420), DRB1*13 (0.1271), DRB1*01 (0.1269), DRB1*11 (0.1216); DQB1*03 (0.3517), DQB1*06 (0.2269). A total of 1702 HLA-A*-B*-C*-DRB1*-DQB1*-haplotypes were revealed in our donor pool. The frequency of nine HLA-haplotypes exceeded 0.01: A*01-B*08-C*07-DRB1*03-DQB1*02 (0.0366), A*03-B*07-C*07-DRB1*15-DQB1*06 (0.0269), A*03-B*35-C*04-DRB1*01-DQB1*05 (0.0238), A*02-B*13-C*06-DRB1*07-DQB1*02 (0.0204), A*02-B*07-C*07-DRB1*15-DQB1*06 (0.0184), A*25-B*18-C*12-DRB1*15-DQB1*06 (0.0127), A*02-B*18-C*07-DRB1*11-DQB1*03 (0.0126), A*02-B*15-C*03-DRB1*04-DQB1*03 (0.0123), A*02-B*41-C*17-DRB1*13-DQB1*03 (0.0109). We carried out a comparative analysis of the HLA-haplotypes distribution for the donors of three Russian registers: Russian Research Institute of Haematology and Transfusiology (St. Petersburg); First St. Petersburg State I. Pavlov Medical University (St. Petersburg); National Medical Research Center for Hematology (Moscow). The six most common HLA-haplotypes among the donors from three Russian registers had the same rank positions and frequencies. The differences of some less common HLA-haplotypes distribution were determined. The results of our study indicate the immunogenetic diversity of the donor pool the Registry of Russian Research Institute of Haematology and Transfusiology. This fact, along with usage of international standards for primary immunogenetic examination is a prerequisite for effective donor search for the patients requiring stem cell transplantation.
5
Street, J., C. Harvey, E. Cook, J. Johnson, and C. Darke. "Three new HLA-DQB1 alleles -DQB1*03:113,DQB1*06:02:15andDQB1*06:129." Tissue Antigens 86, no. 3 (July 23, 2015): 216–17. http://dx.doi.org/10.1111/tan.12619.
Full text
6
Baek, In-Cheol, Eun-Jeong Choi, Dong-Hwan Shin, Hyoung-Jae Kim, Haeyoun Choi, and Tai-Gyu Kim. "Allele and haplotype frequencies of human leukocyte antigen-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 by next generation sequencing-based typing in Koreans in South Korea." PLOS ONE 16, no. 6 (June 21, 2021): e0253619. http://dx.doi.org/10.1371/journal.pone.0253619.
Full textAbstract:
Allele frequencies and haplotype frequencies of HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 have been rarely reported in South Koreans using unambiguous, phase-resolved next generation DNA sequencing. In this study, HLA typing of 11 loci in 173 healthy South Koreans were performed using next generation DNA sequencing with long-range PCR, TruSight® HLA v2 kit, Illumina MiSeqDx platform system, and Assign™ for TruSight™ HLA software. Haplotype frequencies were calculated using the PyPop software. Direct counting methods were used to investigate the association with DRB1 for samples with only one copy of a particular secondary DRB locus. We compared these allele types with the ambiguous allele combinations of the IPD-IMGT/HLA database. We identified 20, 40, 26, 31, 19, 16, 4, and 16 alleles of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, respectively. The number of HLA-DRB3/4/5 alleles was 4, 5, and 3, respectively. The haplotype frequencies of most common haplotypes were as follows: A*33:03:01-B*44:03:01-C*14:03-DRB1*13:02:01-DQB1*06:04:01-DPB1*04:01:01 (2.89%), A*33:03:01-B*44:03:01-C*14:03 (4.91%), DRB1*08:03:02-DQA1*01:03:01-DQB1*06:01:01-DPA1*02:02:02-DPB1*05:01:01 (5.41%), DRB1*04:05:01-DRB4*01:03:01 (12.72%), DQA1*01:03:01-DQB1*06:01:01 (13.01%), and DPA1*02:02:02-DPB1*05:01:01 (30.83%). In samples with only one copy of a specific secondary DRB locus, we examined its association with DRB1. We, thus, resolved 10 allele ambiguities in HLA-B, -C (each exon 2+3), -DRB1, -DQB1, -DQA1, and -DPB1 (each exon 2) of the IPD-IMGT/HLA database. Korean population was geographically close to Japanese and Han Chinese populations in the genetic distances by multidimensional scaling (MDS) plots. The information obtained by HLA typing of the 11 extended loci by next generation sequencing may be useful for more exact diagnostic tests on various transplantations and the genetic population relationship studies in South Koreans.
7
Werneck, Lineu Cesar, Paulo José Lorenzoni, Cláudia Suemi Kamoi Kay, and Rosana Herminia Scola. "Multiple sclerosis: disease modifying therapy and the human leukocyte antigen." Arquivos de Neuro-Psiquiatria 76, no. 10 (October 2018): 697–704. http://dx.doi.org/10.1590/0004-282x20180103.
Full textAbstract:
ABSTRACT Objective: To investigate the potential relationship between the human leukocyte antigen (HLA) type (class I and II) and the response to several disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS). Methods: We analyzed clinical data of 87 patients with MS at the beginning and end of each type of DMT including the disease duration, Expanded Disability Status Scale and Multiple Sclerosis Severity Score (MSSS). Genotyping of HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B and HLA-C alleles were identified using high-resolution techniques. Statistical correlation between the HLA type and response to DMTs was done using the initial and final MSSS. Results: Statistical relationships (p < 0.05) were found for only 15 of 245 alleles tested. There was a reduction in the MSSS for patients treated with corticosteroids (DRB1*15:01, DPB1*04:01, DQB1*02:01 and DQB1*03:01), azathioprine (DRB1*03:01, DPB1*04:01, DQB1*03:02, DQB1*06:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 and DQB1*03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) and interferon β-1b (DQB1*02:01). Conclusion: These findings suggest a few relationships between the HLA and response to DMTs in the disability for some types of HLA class I and II alleles in a specific subset of MS patients.
8
Tshabalala, Mqondisi, Charlotte Ingram, Terry Schlaphoff, Veronica Borrill, Alan Christoffels, and Michael S. Pepper. "Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry." Journal of Immunology Research 2018 (2018): 1–8. http://dx.doi.org/10.1155/2018/2031571.
Full textAbstract:
Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies.
9
Zawadzka-Starczewska, Katarzyna, Bogusław Tymoniuk, Bartłomiej Stasiak, Andrzej Lewiński, and Magdalena Stasiak. "Actual Associations between HLA Haplotype and Graves’ Disease Development." Journal of Clinical Medicine 11, no. 9 (April 29, 2022): 2492. http://dx.doi.org/10.3390/jcm11092492.
Full textAbstract:
The association between HLA and the risk of Graves’ disease (GD) has been analyzed for many years. However, the results were often inconsistent and mostly regarded Asian populations. The purpose of our study was to perform HLA genotyping using a next-generation sequencing (NGS) method in Caucasians, to find out which alleles are eventually correlated with GD morbidity as well as which of them can be considered protective. HLA-A, -B, -C, -DQB1, -DRB1 were genotyped using a next-generation sequencing method in 2376 persons, including 159 GD patients and 2217 healthy controls. We have demonstrated a significant association between the risk of GD and the following alleles: HLA-B*08:01, -B*39:06, -B*37:01, -C*07:01, -C*14:02, -C*03:02, -C*17:01, -DRB1*03:01, -DRB1*11:01, -DRB1*13:03, -DRB1*01:03, -DRB1*14:01, -DQB1*03:01, DQB1*02:01. The alleles HLA-B*39:06, -B*37:01, -C*14:02, -C*03:02, -C*17:01, -DRB1*14:01 are novel GD-associated, previously not-reported independent ones with no linkage disequilibrium with other high-risk alleles. On the other hand, the frequencies of HLA-B*07:02, -C*07:02, -C*03:04, DRB1*07:01, -DQB1*02:02, -DQB1*03:03 were significantly lower in GD compared to controls. This study demonstrated the actual relationships between HLA and GD based on the NGS method and provided a novel set of alleles as a reliable tool for an individual personalized risk assessment.
10
Rivera-Pirela, Sergio E., Miriam Echeverría, Pedro Salcedo, Georgina Márquez, Zuhey Carrillo, Yennis Parra, Ana María Cipriani, José R. Núñez, and Melchor Álvarez de Mon. "HLA DRB1*, DQB1*, DPA1*, and DPB1* and their association with the pathogenesis of leukemia in the population of Venezuela." Revista Alergia México 63, no. 3 (August 27, 2016): 237. http://dx.doi.org/10.29262/ram.v63i3.147.
Full textAbstract:
Antecedentes: El complejo de histocompatibilidad es un factor que influye en la patogénesis de las leucemias.Objetivos: se evaluó la presencia de alelos HLA clase II DRB1*, DQB1*, DPA1* y DPB1* en 47 pacientes con leucemia linfoide aguda (LLA) y 48 con leucemia mieloide crónica (LMC), para compararlos con 48 voluntarios sanos de Zulia, Venezuela, y determinar las posibles asociaciones de HLA con las leucemias.Métodos: Se utilizó la técnica de PCR-SSP de baja y alta resolución para las regiones HLA clase II DRB1*, DQB1*, DPA1* y DPB1* conforme las instrucciones del KIT Olerup SSP Genovision.Resultados: Los alelos HLA-DRB1*14, especialmente DRB1*14:21, -DPA1*1:06, -DPA1*01:03,-DPA1*02:01, y los haplotipos HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 tuvieron asociación con LMC (RR > 3); los alelos HLA-DRB1*13, -DQB1*02, -DPA1*01:05, -DPA1*01:09 y los haplotipos HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 resultaron protectores (RR < 1). Los alelos HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 tuvieron asociación positiva con LLA. Los alelos HLA-DPA1*01:09, -DPA1*02:01, -DPB1*02:01, -DPB1*03:01 y los haplotipos HLA-DPA1*01:03-DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01-DPB1*04:02 resultaron asociados negativamente.Conclusiones: La ausencia de asociaciones con la región HLA-DRB1* en LLA y los otros patrones de asociación identificados sugieren marcadas diferencias en las patogénesis de las leucemias, lo que orienta hacia posibles deficiencias en la presentación antigénica para LLA o posibles efectos de mimetismo molecular en LMC.
11
Troshina, Ekaterina, Marina Yukina, Nurana Nuralieva, Evgeny Vasilyev, Olga Rebrova, Ravida Akhmatova, Anna Ikonnikova, et al. "Association of Alleles of Human Leukocyte Antigen Class II Genes and Severity of COVID-19 in Patients of the ‘Red Zone’ of the Endocrinology Research Center, Moscow, Russia." Diseases 10, no. 4 (November 2, 2022): 99. http://dx.doi.org/10.3390/diseases10040099.
Full textAbstract:
The aim of this study was to assess the correlations of clinical features of patients with moderate and severe courses of COVID-19, comorbidity (endocrine, autoimmune, cardiovascular, oncological, and pulmonary diseases), and alleles of the HLA class II system genes. One hundred COVID-19 patients hospitalized in the Endocrinology Research Centre, Moscow, Russia, were analyzed for age, gender, smoking, comorbidity, and invasive mechanical ventilation. Computer tomography was used to assess the severity of the disease. HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles were identified in samples from 100 patients and samples from 327 randomly selected individuals collected in the prepandemic period (control group). There was no association of gender, age, weight, body mass index, smoking, and comorbidity with the severity of COVID-19. Allele DQB1*06:02-8 was more common in patients (p < 0.00005), and DQB1*06:01 and DQB1*05:03 were more common in the control group (p < 0.00005, and p = 0.0011, respectively). DQB1*06:02-8 can probably be considered as predisposing to moderate and severe COVID-19, and DQB1*06:01 can be considered as protective. No association of these alleles with comorbidity was found. Our results suggest that carriers of predisposing alleles, with cardiovascular and non-autoimmune endocrine diseases, should take more stringent preventive measures, and if infected, a more aggressive COVID-19 treatment strategy should be used.
12
Creary, Lisa E., Kalyan C. Mallempati, Sridevi Gangavarapu, Stacy J. Caillier, Jorge R. Oksenberg, and Marcelo A. Fernández-Viňa. "Deconstruction of HLA-DRB1*04:01:01 and HLA-DRB1*15:01:01 class II haplotypes using next-generation sequencing in European-Americans with multiple sclerosis." Multiple Sclerosis Journal 25, no. 6 (April 23, 2018): 772–82. http://dx.doi.org/10.1177/1352458518770019.
Full textAbstract:
Background: The association between HLA-DRB1*15:01 with multiple sclerosis (MS) susceptibility is well established, but the contribution of the tightly associated HLA-DRB5*01:01 allele has not yet been completely ascertained. Similarly, the effects of HLA-DRB1*04:01 alleles and haplotypes, defined at the full-gene resolution level with MS risk remains to be elucidated. Objectives: To characterize the molecular architecture of class II HLA-DR15 and HLA-DR4 haplotypes associated with MS. Methods: Next-generation sequencing was used to determine HLA-DQB1, HLA-DQA1, and HLA-DRB1/4/5 alleles in 1403 unrelated European-American patients and 1425 healthy unrelated controls. Effect sizes of HLA alleles and haplotypes on MS risk were measured by odds ratio (OR) with 95% confidence intervals. Results: HLA-DRB1*15:01:01:01SG (OR = 3.20, p < 2.2E–16), HLA-DRB5*01:01:01 (OR = 2.96, p < 2.2E–16), and HLA-DRB5*01:01:01v1_STR1 (OR = 8.18, p = 4.3E–05) alleles all occurred at significantly higher frequencies in MS patients compared to controls. The most significant predis-posing haplotypes were HLA-DQB1*06:02:01~ HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01 and HLA-DQB1*06:02:01~HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01v1_STR1 (OR = 3.19, p < 2.2E–16; OR = 9.30, p = 9.7E–05, respectively). Analyses of the HLA-DRB1*04 cohort in the absence of HLA-DRB1*15:01 haplotypes revealed that the HLA-DQB1*03:01:01:01~HLA-DQA1*03:03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was protective (OR = 0.64, p = 0.028), whereas the HLA-DQB1*03:02:01~HLA-DQA1*03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was associated with MS susceptibility (OR = 1.66, p = 4.9E–03). Conclusion: HLA-DR15 haplotypes, including genomic variants of HLA-DRB5, and HLA-DR4 haplotypes affect MS risk.
13
Madore, Anne-Marie, Vanessa T. Vaillancourt, Yuka Asai, Reza Alizadehfar, Moshe Ben-Shoshan, Deborah L. Michel, Anita L. Kozyrskyj, et al. "HLA-DQB1*02 and DQB1*06:03P are associated with peanut allergy." European Journal of Human Genetics 21, no. 10 (February 27, 2013): 1181–84. http://dx.doi.org/10.1038/ejhg.2013.13.
Full text
14
Tailor, Arun, Xiaoli Meng, Kareena Adair, John Farrell, James C. Waddington, Ann Daly, Munir Pirmohamed, Gordon Dear, B. Kevin Park, and Dean J. Naisbitt. "HLA DRB1*15:01-DQB1*06:02-Restricted Human CD4+ T Cells Are Selectively Activated With Amoxicillin-Peptide Adducts." Toxicological Sciences 178, no. 1 (August 10, 2020): 115–26. http://dx.doi.org/10.1093/toxsci/kfaa128.
Full textAbstract:
Abstract Amoxicillin-clavulanate is the most common cause of idiosyncratic drug-induced liver injury (DILI). Drug-specific CD4+ T cells have been detected in patients with DILI, suggestive of an immune etiology. Furthermore, genetic associations including the human leucocyte antigen (HLA) DRB1*15:01-DQB1*06:02 haplotype influence susceptibility. Amoxicillin forms protein adducts that are postulated to activate T cells, by conjugating with lysine residues. However, a role for such adducts has not been described. This study aimed to (1) investigate whether amoxicillin-modified HLA-DRB1*15:01-DQB1*06:02 binding peptides selectively activate DILI patient T cells and (2) define the nature of the T-cell response with respective to antigen structure. Peptides carrying lysine residues for amoxicillin binding in positions (KP) 2-6 and anchors for the HLA-DRB1*15:01-DQB1*06:02 haplotype were designed. The amoxicillin-modified peptides were characterized by mass spectrometry prior to culturing with patient peripheral blood mononuclear cell. T-cell clones were then tested for specificity with amoxicillin, unmodified- and amoxicillin-modified peptides, and structural variants. Amoxicillin-modified KP-2 and KP-3 peptide-specific CD4+ clones proliferated and secreted interferon gamma (IFN-γ), interleukin (IL)-10, perforin and/or IL-17/IL-22 in a dose-dependent manner and displayed no cross-reactivity with amoxicillin, unmodified peptide or with positional derivatives. The T cells response was HLA class II restricted and the amoxicillin-modified peptides bound selectively to HLA-DRB1*15:01 and/or DQB1*06:02. To conclude, we show that amoxicillin-modified peptides bind to both components of the risk haplotype to stimulate DILI patient T cells and describe the importance of the position of nucleophilic lysine residue in the HLA binding peptide sequence.
15
Ameen, Reem, Salem H. Al Shemmari, and Steven G. E. Marsh. "HLA Haplotype Frequencies and Genetic Profiles of the Kuwaiti Population." Medical Principles and Practice 29, no. 1 (March 15, 2019): 39–45. http://dx.doi.org/10.1159/000499593.
Full textAbstract:
Objective: The aim of this study was to assess the HLA haplotype frequencies and genetic profiles of the Kuwaiti population. Materials and Methods: Whole venous blood was obtained from 595 healthy, unrelated Kuwaiti volunteers. The study population was genotyped for HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1 and HLA-DQB1) loci using sequence-specific oligonucleotide (SSO) probe-based hybridization and high-resolution HLA genotyping. Haplotype frequencies were estimated using an implementation of the expectation maximization algorithm that resolves both phase and allelic ambiguity. The Kuwaiti population was compared with other populations from the US National Marrow Donor Program (NMDP), by running a principal component analysis (PCA) on the relevant haplotype frequencies. Results: The most common HLA class I alleles in Kuwait were HLA-A*02:01g, HLA-C*06:02g, and HLA-B*50:01g with frequencies of 16, 14, and 12%, respectively. The most common HLA class II alleles in Kuwait were HLA-DQB1*02:01g and HLA-DRB1*07:01 with frequencies of 29.7 and 16.5%, respectively. The most common Kuwaiti haplotype observed was HLA-A*02:01g∼HLA-C*06:02g∼HLA-B*50:01g∼HLA-DRB1*07:01∼HLA-DQB1*02:01g at a frequency of 2.3%. The PCA demonstrated close genetic proximity of the Kuwaiti population with Middle Eastern, Southeast Asian, and North African populations in the NMDP. Conclusion: Identifying the haplotype diversity in the Kuwaiti population will contribute to the selection of an HLA-match for HSCT, disease associations, pharmacogenomics, and knowledge of population HLA diversity.
16
Laivacuma, Sniedze, Jeļena Eglīte, Aleksejs Derovs, and Ludmila Vīksna. "Distribution of HLA Allele Frequencies in Patients with Cystic and Alveolar Echinococcosis in Latvia." Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences. 73, no. 4 (August 1, 2019): 296–303. http://dx.doi.org/10.2478/prolas-2019-0047.
Full textAbstract:
Abstract The aim of this study was to assess the relationship between HLA Class II alleles in two groups of patients in Latvia: patients with cystic and alveolar echinococcosis. The study included 37 patients from the Rīga East Clinical University Hospital with echinococcosis (29 patients with cystic echinococcosis and eight patients with alveolar echinococcosis) and 100 healthy control persons without echinococcosis. HLA Class II allele genotyping was performed using Real-time polymerase chain reaction–sequence specific primer (RT-PCR-SSP). The odds ratios (OR), with 95% confidence intervals (95% CI), were calculated using statistical analysis performed with IBM SPSS Statistics for Windows, Version 22.0, to evaluate the risk of developing the disease in an individual having a particular HLA genotype. In the case of cystic echinococcosis a more severe course of a disease can be anticipated in the presence of HLA-DRB1 alleles *17:01 and *07:01, -DQB1 *03:02, and *03:01, -DQA1*04:01 and haplotypes HLA-DRB1*04:01/-DQB1*03:01/ -DQA1*03:01, HLADRB1*11:01/ -DQB1*03:01 /-DQA1*05:01. However, in the group with alveolar echinococcosis it was associated with the HLA-DRB1 alleles *17:01 and *07:01, -DQB1 *05:01 and haplotypes HLA- DRB1*17:01/-DQB1*02:01-2/-DQA1*01:01, HLA-DRB1*11:01/ -DQB1*03:01/-DQA1*01:03 and HLA-DRB1*11:01/-DQB1*03:01/-DQA1*03:01. HLADRB1*15:01/-DQÂ1*06:02-8/-DQA1*05:01 and HLA-DRB1*13:01/-DQB1*02:01-2/-DQA1*05:01 haplotypes were protective in all patient groups. The limitations of this exploratory study indicate that a broader study needs to be conducted for revealing specific risk and protective HLA Class II haplotypes for patients with cystic and alveolar echinococcosis in Latvia.
17
Ueda, Sho, Daisuke Oryoji, Ken Yamamoto, Jaeduk Yoshimura Noh, Ken Okamura, Mitsuhiko Noda, Koichi Kashiwase, et al. "Identification of Independent Susceptible and Protective HLA Alleles in Japanese Autoimmune Thyroid Disease and Their Epistasis." Journal of Clinical Endocrinology & Metabolism 99, no. 2 (February 1, 2014): E379—E383. http://dx.doi.org/10.1210/jc.2013-2841.
Full textAbstract:
Background: Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto thyroiditis (HT), which partially share immunological features. Determining the genetic basis that distinguishes GD and HT is a key to understanding the differences between these 2 related diseases. Aim: The aims of this study were to identify HLA antigens that can explain the immunopathological difference between GD and HT and to elucidate epistatic interactions between protective and susceptible HLA alleles, which can delineate the distinct function of HLA in AITD etiology. Design: We genotyped 991 patients with AITD (547 patients with GD and 444 patients with HT) and 481 control subjects at the HLA-A, HLA-C, HLA-B, DRB1, DQB1, and DPB1 loci. A direct comparison of HLA antigen frequencies between GD and HT was performed. We further analyzed an epistatic interaction between the susceptible and protective HLA alleles in the development of GD and HT. Results: We identified 4 and 2 susceptible HLA molecules primarily associated with GD and HT, respectively, HLA-B*35:01, HLA-B*46:01, HLA-DRB1*14:03, and HLA-DPB1*05:01 for GD and HLA-A*02:07 and HLA-DRB4 for HT. In a direct comparison between GD and HT, we identified GD-specific susceptible class II molecules, HLA-DP5 (HLA-DPB1*05:01; Pc = 1.0 × 10−9) and HLA-DR14 (HLA-DRB*14:03; Pc = .0018). In contrast, HLA components on 3 common haplotypes in Japanese showed significant protective effects against the development of GD and HT (HLA-A*24:02-C*12:02-B*52:01-DRB1*15:02-DQB1*06:01-DPB1*09:01 and HLA-A*24:02-C*07:02-B*07:02-DRB1*01:01-DQB1*05:01-DPB1*04:02 haplotypes for GD and HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01 haplotype for GD and HT). Interestingly, the representative protective HLA, HLA-DR13 (HLA-DRB1*13:02), was epistatic to susceptible HLA-DP5 in controlling the development of GD. Conclusion: We show that HLA exerts a dual function, susceptibility and resistance, in controlling the development of GD and HT. We also show that the protective HLA allele is partially epistatic to the susceptible HLA allele in GD.
18
Le, Wei-Bo, Jing-Song Shi, Yang Fan, and Si-Wen Gong. "HLA Alleles and Prognosis of PLA2R-Related Membranous Nephropathy." Clinical Journal of the American Society of Nephrology 16, no. 8 (June 3, 2021): 1221–27. http://dx.doi.org/10.2215/cjn.18021120.
Full textAbstract:
Background and objectivesAssociations between HLA alleles and susceptibility to M-type phospholipase A2 receptor (PLA2R)–related membranous nephropathy have been well defined previously in Chinese patients. However, the relationships between HLA alleles and kidney outcome remain unclear.Design, setting, participants, & measurementsFive HLA genes (DRB1, DQA1, DQB1, DRB3, and DRB5) were genotyped in a prospective cohort of 392 patients with PLA2R-related membranous nephropathy. The associations between HLA alleles and kidney outcomes were studied.ResultsA total of 79 HLA alleles were identified in this study. Four HLA alleles, DRB1*13:01 (n=12; hazard ratio, 3.7; 95% confidence interval, 1.8 to 7.8; P<0.001), DQB1*06:03 (n=12; hazard ratio, 3.7; 95% confidence interval, 1.8 to 7.8; P<0.001), DRB1*04:05 (n=12; hazard ratio, 3.8; 95% confidence interval, 1.5 to 9.5; P=0.004), and DQB1*03:02 (n=21; hazard ratio, 3.1; 95% confidence interval, 1.4 to 6.7; P=0.005), were associated with a ≥40% eGFR decline during follow-up. DRB1*13:01 and DQB1*06:03 were tightly linked with each other. Forty-four of the 392 patients (11%) carried at least one of the four identified risk HLA alleles in this study. Compared with patients who were negative for all risk HLA alleles, those carrying at least one risk HLA allele had a significant risk of a ≥40% eGFR decline during follow-up (hazard ratio, 3.9; 95% confidence interval, 2.3 to 6.7; P<0.001). After adjusting for age, sex, proteinuria, albumin, eGFR, and anti-PLA2R antibody levels, multivariable Cox analysis showed that patients carrying any of the four risk HLA alleles remained associated with a higher risk of a ≥40% decline in eGFR (hazard ratio, 4.1; 95% confidence interval, 2.3 to 7.1; P<0.001).ConclusionsCarrying any of the HLA alleles, DRB1*13:01/DQB1*06:03, DRB1*04:05, and DQB1*03:02, was independently associated with poor prognosis in Chinese patients with PLA2R-related membranous nephropathy.
19
Loginova, Maria, Olga Makhova, and Igor Paramonov. "Characterization of two new HLA alleles, HLA‐A *02:942 and HLA‐DQB1 *06:02:47." HLA 97, no. 1 (September 22, 2020): 66–67. http://dx.doi.org/10.1111/tan.14070.
Full text
20
De Silvestri, A., C. Capittini, G. Mallucci, R. Bergamaschi, C. Rebuffi, A. Pasi, M. Martinetti, and C. Tinelli. "The Involvement of HLA Class II Alleles in Multiple Sclerosis: A Systematic Review with Meta-analysis." Disease Markers 2019 (November 6, 2019): 1–7. http://dx.doi.org/10.1155/2019/1409069.
Full textAbstract:
Multiple Sclerosis (MS) displays a heterogeneous clinical onset and progression, which are mostly unpredictable, but demyelination of the central nervous system (CNS) leads to substantial deficits of sensory, motor, autonomic, and neurocognitive functions. Considering all genetic studies on MS, including the advanced genome-wide association studies, the risk linked to HLA alleles remains the highest among other susceptibility genetic variants. However, given the genetic variability of HLA alleles in different ethnic groups, we conducted a systematic review of reviews and meta-analyses aiming at summarizing all the results on the association between MS and HLA class II genes. We systematically searched meta-analyses and systematic reviews dealing with MS and HLA in all ethnicities. From 154 records, we included 5 articles collecting HLA data from 15,232 MS patients and 24,194 ethnically matched controls. DRB1∗15 (OR ranging from 1.39 in Chinese Han to 2.59 in Caucasians) and DQB1∗06:02 (OR ranging from 1.91 in Caucasians to 2.49 in Colombian) alleles confer an increased risk for MS transethnically (Caucasians, Chinese, South Americans, Carribeans, Middle Easterners, Japanese, and North Africans). DRB1∗01, DRB1∗09, DRB1∗11, DRB1∗12, and DRB1∗16 alleles were protective, in agreement with the type of amino-acidic (aa) residues (ranging from position 9 to 90) included in pockets 1, 4, 6, 7, and 9, which are most involved in peptide presentation. Changes in aa residues affect the capability of HLA molecules in binding myelin peptides. DQB1∗06:02 risk allele seems to be the most interesting target as humanized mice expressing only DQB1∗06:02 develop MS-like disease mediated by autoimmune reactions against myelin oligodendrocytic basic protein that stabilizes the myelin. Our summary of results from a high number of patients and controls suggests that allelic variants from both DQB1 and DRB1 genes are equally involved in MS susceptibility/protection transethnically.
21
Fagbemi, Kaossarath A., Thierry C. Marc Medehouenou, Simon Azonbakin, Marius Adjagba, Razack Osseni, Jocelyne Ahoueya, Arnaud Agbanlinsou, Raphael Darboux, Lamine Baba-Moussa, and Anatole Laleye. "HLA Class II Allele, Haplotype, and Genotype Associations with Type 1 Diabetes in Benin: A Pilot Study." Journal of Diabetes Research 2017 (2017): 1–4. http://dx.doi.org/10.1155/2017/6053764.
Full textAbstract:
Background. Several studies have reported the implication of HLA-DR/DQ loci in the susceptibility to type 1 diabetes (T1D). Since no such study has yet been performed in Benin, this pilot one aimed at assessing HLA class II allele, haplotype, and genotype associations with T1D. Material and Methods. Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated controls by means of the PCR-SSP method. The diagnosis of T1D was set up according to American Diabetes Association criteria. Odds ratio (OR) and its 95% confidence interval (95% CI) were calculated to assess the associations between T1D and HLA alleles, haplotypes, and genotypes. Results. Participants were aged 1–24 years. T1D was significantly associated with DR3, DQA1∗05:01, DQB1∗02:01, and DR3-DR4. No significant associations were observed with DR4, DQB1∗03:02, and DQB1∗06:02. Conclusion. Certain HLA class II alleles, haplotypes, and genotypes were related to T1D and may be used as genetic susceptibility markers to T1D in Benin.
22
Han, Fang, Ling Lin, Barbara Schormair, Fabio Pizza, Giuseppe Plazzi, Hanna M. Ollila, Sona Nevsimalova, et al. "HLA DQB1*06:02 Negative Narcolepsy with Hypocretin/Orexin Deficiency." Sleep 37, no. 10 (October 1, 2014): 1601–8. http://dx.doi.org/10.5665/sleep.4066.
Full text
23
Mohammad, Tawfeeq, Mohammad Al-Kurtas, Haider Zalzala, Batool Mahdi, Hyam Raouf, Laheeb Abid, and Zena Nehad. "Human leukocytes antigen HLA-DQB1 determine susceptibility to thyroid disease." Ibnosina Journal of Medicine and Biomedical Sciences 07, no. 06 (December 2015): 219–22. http://dx.doi.org/10.4103/1947-489x.210288.
Full textAbstract:
Background: Thyroid disease is a common disease in women of the reproductive age. This disease arises due to complex interactions between environmental and genetic factors. However, the interactions between genes and environment are yet well defined. Among the main susceptibility genes that have been identified is the HLA-DQB1 gene locus. The major environmental factors include iodine, medications, infection, smoking, and possibly stress. Aim of study: To ascertain the association between HLA-DQB1 alleles and goitrous thyroid disease in a sample of Iraqi Arab Muslims. Patients and methods: A cross sectional case-control comparative study was carried out. Patients with thyroid disorders who attended this hospital in the period from September 2013 to June 2014 for thyroidectomy were studied. HLA-DQB1genotyping was done using a panel of sequence-specific oligonucleotide probes (SSOP) using HLA-DQB1 amplification and hybridization kits (SSO HLA type DQB1 plus and Mastermix for HLA type DQB1 Amp plus) using automated method by AutoLipa-48. Results: There was an increased frequency of HLADQB1*03:01and 0601 in control group compared with patients group (P=0.005, Odds ratio=0.0164, 95% CI: 0.0009-0.2926) and (P=0.01, Odd ratio=0.1667, 95% CI: 0.0412 to 0.6750) respectively. Other alleles like HLA-DQB1* 0202, 03:02, 0501 and 06:02 were detected in the patients' group but not in controls. Conclusions: HLA alleles have an effect on development thyroid disease. HLADQB1* 0301 and 0601 is a protective in Iraqi Arab Muslims individuals.
24
Diego, Vincent P., Bernadette W. Luu, Alexis Garza, Marco Hofmann, Marcio A. Almeida, Jerry S. Powell, Long V. Dinh, et al. "Disentangling the Effects of HLA DRB1*15:01 and DQB1*06:02 to Establish the True HLA Risk Allele for Inhibitor Development in the Treatment of Hemophilia A." Blood 136, Supplement 1 (November 5, 2020): 1–2. http://dx.doi.org/10.1182/blood-2020-142716.
Full textAbstract:
The HLA haplotype DRB1*15:01/DQB1*06:02 has been shown to be associated with the development of inhibitory antibodies ("inhibitors") against therapeutic FVIII (tFVIII) proteins in Hemophilia A (HA) patients. Moreover, this same haplotype has also been implicated with an increased risk for the development of multiple sclerosis, narcolepsy, and drug-induced-hypersensitivity and -liver-injury. Recent reports in the literature have indicated that the alleles of this haplotype may have differential effects on immunogenicity despite the fact that they are in strong linkage disequilibrium (LD). Thus, the question arises as to which of the two constituent alleles of this haplotype is the true HLA risk allele. To address this question we analyzed peptidomic profiling data on HLA-class-II (HLAcII)-presented peptides from dendritic cell (DC)-protein processing and presentation assays (PPPAs) performed in two independent experiments performed by Peyron et al. (2018) and Diego et al. (2020) which reported results on both the HLA-DQ and -DR isomers. The tFVIII in both experiments is full-length recombinant FVIII (FL-rFVIII). We performed log-linear mixed model analyses under two models, where the dependent variable in both models is the logarithm of the expected peptide count. Under Model 1, we analyzed in the fixed effect component of the model a single HLA allele predictor variable consisting of 10 levels represented by distinct DRB1 and DQB1 alleles (4 and 6 levels, respectively). Under this model, we analyzed in the random effects component of the model variables for individuals (8 and 9 levels from Peyron et al. and Diego et al., respectively), experiments (2 levels for Peyron et al. and Diego et al.), and HLA isomers (2 levels for DQ and DR). The random effects component of the model serves to reduce the error (or "noise") in our estimation of the predictive effect of HLA alleles for the peptide counts by accounting for the clustering due to individuals, experiments, and isomers. This approach therefore can be understood as maximizing the signal-to-noise ratio. Model 2 was more focused in that the single HLA allele predictor variable in the fixed effect component consisted of only DQB1*06:02 and DRB1*15:01. Model 2 was also simpler in that we only accounted for two random effect variables, namely for individuals (in this case 2 and 6 levels for Peyron et al. and Diego et al., respectively) and experiments. Thus, Model 2 is a direct head-to-head comparison of the two main HLA alleles of interest. The Model 1 results are reported in Figure 1A and B, where it can be seen that relative to the baseline reference allele provided by DQB1*02:01, both DQB1*06:02 and DRB1*15:01 are at significantly increased risk of contributing to the overall peptide count. Results are reported as risk ratios (RRs) and their associated 95% confidence interval lower and upper bounds (95% CI LB and 95% CI UB). For DQB1*06:02 and DRB1*15:01 respectively, we found a RR (95% CI LB, 95% CI UB) of 1.76 (1.24, 2.50) and 14.16 (10.38, 19.33). Because they are compared to the same baseline, the two RRs may also be directly compared, thus showing that DRB1*15:01 contributes significantly more to the overall peptide count than DQB1*06:02. Under Model 2 (the head-to-head comparison), the RR for the DRB1*15:01 allele against the baseline DQB1*06:02 allele is 7.00 (5.80, 8.44) (Figure 2A and B). These results contribute to the field of precision medicine because they demonstrate that even in the case of alleles in tight LD, their effects can be effectively disentangled by a DC-PPPA and a log-linear mixed model analysis. Our results support the conclusion that in regard to the well-known risk haplotype of DQB1*06:02/DRB1*15:01, the true HLA risk allele seems to be DRB1*15:01. Disclosures Luu: Haplogenics Corporation: Current Employment. Hofmann:CSL Behring: Current Employment. Powell:Haplogenics Corporation: Membership on an entity's Board of Directors or advisory committees. Dinh:Haplogenics Corporation: Current Employment. Escobar:National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Maraskovsky:CSL Behring: Current Employment. Howard:Haplogenics Corporation: Membership on an entity's Board of Directors or advisory committees.
25
Lehmann, Claudia, Henry Loeffler-Wirth, Vera Balz, Juergen Enczmann, Ramona Landgraf, Nicole Lakowa, Thomas Gruenewald, Johannes C. Fischer, and Ilias Doxiadis. "Immunogenetic Predisposition to SARS-CoV-2 Infection." Biology 12, no. 1 (December 25, 2022): 37. http://dx.doi.org/10.3390/biology12010037.
Full textAbstract:
Herein, we included 527 individuals from two Hospitals, Chemnitz and University-Hospital Leipzig. In total, 199 were negative for PCR and 328 were positive upon first admission. We used next generation sequencing for HLA-A, B, C, DRB1, DRB345, DQA1, DQB1, DPA1, and DPB1, and in some cases, HLA-E, F, G, and H. Furthermore, we molecularly defined 22 blood group systems comprising 26 genes and 5 platelet antigen genes. We observed a significant enrichment of homozygosity for DQA/DQB in the positive group. Within the negative subjects, HLA-B*57:01, HLA-B*55:01, DRB1*13:01, and DRB1*01:01 were enriched, and in the positive group, homozygosity for DQA/DQB, DRB1*09:01, and DRB1*15:01 was observed. DQA1*01:01, DQA1*02:01, and DQA1*01:03 were enriched in the negative group. HLA-DQB1*06:02 was enriched in the positive group, and HLA-DQB1*05:01 and HLA-DQB1*06:03 were enriched in the negative group. For the blood group systems MNS, RH, LE, FY, JK, YT, DO, and KN, enrichment was seen in both groups, depending on the antigen under observation. Homozygosity for D-positive RHD alleles, as well as the phenotypes M-N+ of the MNS blood group system and Yk(a-) of the KN system, were enriched in the positive group. All of these significances disappeared upon correction. Subjects who carried homozygous HPA-1a were more frequent in the negative group, contrasting with the finding that HPA-1ab was enriched in the positive group.
26
Zhang, Lin, Yuan, Lin, and Huang. "HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups." Genes 10, no. 9 (September 13, 2019): 710. http://dx.doi.org/10.3390/genes10090710.
Full textAbstract:
Latent autoimmune diabetes in adults (LADA) was recently demonstrated to be the most frequent form of adult-onset autoimmune diabetes mellitus. Case–control studies have investigated the relationship between human leukocyte antigen (HLA)-DQB1 and HLA-DRB1 polymorphisms and LADA risk, but their conclusions are inconsistent. This study aimed to more precisely explore the correlation between these HLA gene variants and LADA development. Eight databases, including PubMed, Embase, and Medline, were systematically searched for relevant studies up to September 15, 2018. We performed this retrospective study using meta-analysis and relative predispositional effect (RPE) methods. The meta-analysis results indicated that DQB1*02 (odds ratio (OR) = 1.685, pc < 0.005) and DQB1*06 (OR = 0.604, pc = 0.010) have opposite effects on susceptibility to LADA, while a significant decrease in LADA risk caused by DQB1*05 (OR = 0.764, pc = 0.100) disappeared upon Bonferroni correction. The RPE method confirmed the roles of DQB1*02 (χ² = 46.475, p < 0.001) and DQB1*06 (χ² = 17.883, p < 0.001) and further suggested protective effects of DQB1*05 (χ² = 16.496, p < 0.001). Additionally, the meta-analysis results showed that DRB1*03 (OR = 2.685, pc < 0.013), DRB1*04 (OR = 1.954, pc < 0.013), and DRB1*09 (OR = 1.346, pc < 0.013) are associated with increased LADA risk, while DRB1*12 (OR = 0.600, pc < 0.013) and DRB1*13 (OR = 0.583, pc < 0.013) carriers have a decreased risk of developing LADA. Furthermore, the RPE method revealed that DRB1*03 (χ² = 98.754, p < 0.001), DRB1*04 (χ² = 94.685, p < 0.001), DRB1*09 (χ² = 40.489, p < 0.001), DRB1*01 (χ² = 12.181, p < 0.001), DRB1*07 (χ² = 10.882, p = 0.001), and DRB1*08 (χ² = 5.000, p = 0.025) play protective roles against LADA. LADA showed a close relationship with genetic polymorphisms of HLA-DQB1 and WHLA-DRB1, which could contribute to a better understanding of disease pathogenesis and the identification of predisposing loci in the diagnosis and treatment of LADA.
27
Osman, Awad E., Imad Brema, Alaa AlQurashi, Abdullah Al-Jurayyan, Benjamin Bradley, and Muaawia A. Hamza. "Single nucleotide polymorphism rs 2070874 at Interleukin-4 is associated with increased risk of type 1 diabetes mellitus independently of human leukocyte antigens." International Journal of Immunopathology and Pharmacology 36 (January 2022): 039463202210903. http://dx.doi.org/10.1177/03946320221090330.
Full textAbstract:
Introduction Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of insulin-producing pancreatic beta (β-) cells. Previous studies suggested an imbalance between and pro- and anti-inflammatory cytokines exacerbates T1DM development. Objectives We aimed to test the hypothesis that patients with T1DM carry a higher frequency of regulatory genes associated with low levels of the anti-inflammatory cytokines interleukin-4 (IL-4), its receptor (IL-4R), and interleukin-10 (IL-10). Methods Accordingly, we compared frequencies of five different single nucleotide polymorphisms (SNPs) in T1DM patients and healthy controls who had been typed for HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Results The frequencies of rs2070874 (IL-4) alleles C and T differed between T1DM patients and controls (cp = 0.0065), as did their codominant (cp = 0.026) and recessive (cp = 0.015) models. Increased frequencies were observed in T1DM patients for HLA alleles: DRB1*03 (pc < 0.0013), DRB1*04 (cp = 0.0169), DQA1*03 (cp = 0.0222), DQA1*05 (cp < 0.0006), DQB1*02 (cp = 0.0005), and DQB1*06 (cp < 0.0005). And lower frequencies were observed for: DRB1*07 (cp = 0.0078), DRB1*11 (cp = 0.0013), DRB1*13 (cp < 0.0364), DRB1*15 (cp < 0.0013), DQA1*01 (cp < 0.0006), and DQA1*02 (cp = 0.0348). Certain DRB1: DQA1: DQB1 haplotypes showed greater frequencies, including, 03:05:02 (p < 0.0001) and 04:03:03 (p = 0.0017), whereas others showed lower frequencies, including, 07:02:02 (p = 0.0032), 11:05:03 (p = 0.0007), and 15:01:06 (p = 0.0002). Stratification for the above HLA haplotypes with rs2070874 C/C exhibited no significant differences between T1DM patients overall and controls. However, when stratified for the vulnerable HLA haplotype (03:05:02/04:03:03), young patients in whom T1DM began at ≤13 years had a higher frequency of the SNP (rs2070874 C/C); a gene associated with low IL-4 production (p < 0.024). Conclusion This study suggests that possession of the rs2070874 C/C genotype, which is associated with low production of IL-4, increases the risk of T1DM in young individuals carrying vulnerable HLA alleles/haplotypes.
28
Kovacs, Andrea A. Z., Naoko Kono, Chia-Hao Wang, Daidong Wang, Toni Frederick, Eva Operskalski, Phyllis C. Tien, et al. "Association of HLA Genotype With T-Cell Activation in Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus–Coinfected Women." Journal of Infectious Diseases 221, no. 7 (November 10, 2019): 1156–66. http://dx.doi.org/10.1093/infdis/jiz589.
Full textAbstract:
Abstract Background Global immune activation and HLA alleles are each associated with the pathogenesis of human immunodeficiency virus (HIV) and hepatitis C virus . Methods We evaluated the relationship between 44 HLA class I and 28 class II alleles and percentages of activated CD8 (CD8+CD38+DR+) and CD4 (CD4+CD38+DR+) T cells in 586 women who were naive to highly active antiretroviral therapy. We used linear generalized estimating equation regression models, adjusting for race/ethnicity, age, HIV load, and hepatitis C virus infection and controlling for multiplicity using a false discovery rate threshold of 0.10. Results Ten HLA alleles were associated with CD8 and/or CD4 T-cell activation. Lower percentages of activated CD8 and/or CD4 T cells were associated with protective alleles B*57:03 (CD8 T cells, −6.6% [P = .002]; CD4 T cells, −2.7% [P = .007]), C*18:01 (CD8 T cells, −6.6%; P < .0008) and DRB1*13:01 (CD4 T cells, −2.7%; P < .0004), and higher percentages were found with B*18:01 (CD8 T cells, 6.2%; P < .0003), a detrimental allele. Other alleles/allele groups associated with activation included C*12:03, group DQA1*01:00, DQB1*03:01, DQB1*03:02, DQB1*06:02, and DQB1*06:03. Conclusion These findings suggest that a person’s HLA type may play a role in modulating T-cell activation independent of viral load and sheds light on the relationship between HLA, T-cell activation, immune control, and HIV pathogenesis.
29
Flesch, B. K., N. Matheis, T. Alt, C. Weinstock, J. Bux, and G. J. Kahaly. "HLA Class II Haplotypes Differentiate Between the Adult Autoimmune Polyglandular Syndrome Types II and III." Journal of Clinical Endocrinology & Metabolism 99, no. 1 (January 1, 2014): E177—E182. http://dx.doi.org/10.1210/jc.2013-2852.
Full textAbstract:
Background: Genetics of the adult autoimmune polyglandular syndrome (APS) is poorly understood. Aim: The aim of this study was to gain further insight into the genetics of the adult APS types. Site: The study was conducted at a university referral center. Methods: The human leukocyte antigen (HLA) class II alleles, haplotypes, and genotypes were determined in a large cohort of patients with APS, autoimmune thyroid disease (AITD), and type 1 diabetes and in healthy controls by the consistent application of high-resolution typing at a four-digit level. Results: Comparison of the allele and haplotype frequencies significantly discriminated patients with APS vs AITD and controls. The HLA class II alleles DRB1*03:01 *04:01, DQA1*03:01, *05:01, DQB1*02:01, and *03:02 were observed more frequently (P < .001) in APS than in AITD and controls, whereas the alleles DRB1*15:01, DQB1*03:01, and *06:02 were underrepresented in APS vs AITD (Pc < .001) and controls (Pc < .01), respectively. The DRB1*03:01-DQA1*05:01-DQB1*02:01 (DR3-DQ2) and DRB1*04:01-DQA1*03:01:DQB1*03:02 (DRB1*04:01-DQ8) haplotypes were overrepresented in APS (Pc < .001). Combination of both haplotypes to a genotype was highly prevalent in APS vs AITD and controls (Pc < .001). Dividing the APS collective into those with Addison's disease (APS type II) and those without Addison's disease but including type 1 diabetes and AITD (APS type III) demonstrated DR3-DQ2/DRB1*04:01-DQ8 as a susceptibility genotype in APS III (Pc < .001), whereas the DR3-DQ2/DRB1*04:04-DQ8 genotype correlated with APS II (Pc < .001). The haplotypes DRB1*11:01-DQA1*05:05-DQB1*03:01 and DRB1*15:01-DQA1*01:02-DQB1*06:02 are protective in APS III but not in type II (Pc < .01). Conclusions: HLA class II haplotypes differentiate between the adult APS types II and III. Susceptible haplotypes favor the development of polyglandular autoimmunity in patients with AITD.
30
Arnaiz-Villena, Antonio, Ester Muñiz, Jose del Palacio-Gruber, Cristina Campos, Javier Alonso-Rubio, Eduardo Gomez-Casado, Filogonio Lopez-Pacheco, Manuel Martin-Villa, and Carlos Silvera. "Ancestry of Amerindians and its Impact in Anthropology, Transplantation, HLA Pharmacogenomics and Epidemiology by HLA Study in Wiwa Colombian Population." Open Medicine Journal 3, no. 1 (December 23, 2016): 269–85. http://dx.doi.org/10.2174/1874220301603010269.
Full textAbstract:
Background:HLA autosomic genes are unique because they conform the most polymorphic human system. Importance of this system is recognized in Medicine for Transplantation, Epidemiology (HLA and disease linkage), Pharmacogenomics (HLA linked to drug side effects) and for defining the origin of populations in both male and female lineages.Objectives:Studying HLA profile of a isolated Amerindian group from North Colombia (Wiwa) in order to draw conclusions about its Preventive Medicine, the genetic relationship with Worldwide populations and America peopling, since this last issue is hotly debated.Methodology:A total of 14,660 HLA chromosomes were included. Peripheral blood was obtained from volunteer blood donors belonging to Wiwa (also named Arsario) ethnic group. HLA-A, -B, -C, -DRB1 and -DQB1 genes were analyzed by standard methods. Wiwa Amerindians relationships with others were calculated by using Arlequin, Dispan and Vista software computer packages.Results:Extended HLA, -A, -B, -C, -DRB1 and -DQB1 haplotypes have been studied for the first time in this population. Classical Amerindian haplotypes have been found and also new Wiwa (Arsario) Amerindian haplotypes. New haplotypes are A*68:01 - B*15:01 - C*03:03 - DRB1*14:02 - DQB1*03:02, A*11:01 - B*07:02 - C*07:02 - DRB1*15:03 - DQB1*06:02 and A*68:01 - B*15:01 - C*03:04 - DRB1*14:02 - DQB1*03:01.Conclusion:They have been reached after exhaustive comparisons of Wiwa with other Amerindians and Worldwide populations by using genetic distances, Neighbor Joining trees, correspondence analysis and specific group of alleles which are common and frequent in both Amerindians and Pacific Islanders. They are: 1) The Americas First Inhabitants have been probably come through Bering Strait and also through Pacific (from Austronesia and Asia) and Atlantic (from Europe) routes. A bidirectional gene flow is not discarded. 2) Genetic HLA Amerindian profile is separated from that of other Worldwide populations. 3) Amerindians geographical proximity groups’ relatedness is not concordant with HLA genetic relatedness, neither with language. This may be explained by a substantial population decrease that occurred after Europeans invaded America in 1492 and carried new pathogens and epidemics. 4) Our results are also useful for Wiwa and other Amerindians future preventive medicine (HLA linked diseases), HLA pharmacogenomics and transplantation regional programs.
31
Hartmann, Felix J., Raphaël Bernard-Valnet, Clémence Quériault, Dunja Mrdjen, Lukas M. Weber, Edoardo Galli, Carsten Krieg, et al. "High-dimensional single-cell analysis reveals the immune signature of narcolepsy." Journal of Experimental Medicine 213, no. 12 (November 7, 2016): 2621–33. http://dx.doi.org/10.1084/jem.20160897.
Full textAbstract:
Narcolepsy type 1 is a devastating neurological sleep disorder resulting from the destruction of orexin-producing neurons in the central nervous system (CNS). Despite its striking association with the HLA-DQB1*06:02 allele, the autoimmune etiology of narcolepsy has remained largely hypothetical. Here, we compared peripheral mononucleated cells from narcolepsy patients with HLA-DQB1*06:02-matched healthy controls using high-dimensional mass cytometry in combination with algorithm-guided data analysis. Narcolepsy patients displayed multifaceted immune activation in CD4+ and CD8+ T cells dominated by elevated levels of B cell–supporting cytokines. Additionally, T cells from narcolepsy patients showed increased production of the proinflammatory cytokines IL-2 and TNF. Although it remains to be established whether these changes are primary to an autoimmune process in narcolepsy or secondary to orexin deficiency, these findings are indicative of inflammatory processes in the pathogenesis of this enigmatic disease.
32
Ananeva, Anastasiia, Nailia Osipova, Anna Andryushkina, and Elena Shagimardanova. "Identification of the novel HLA‐DQB1 , allele DQB1 *06:02:44 by next‐generation sequencing." HLA 97, no. 1 (October 8, 2020): 91–92. http://dx.doi.org/10.1111/tan.14081.
Full text
33
Jia, Xiaoyuan, Tomoko Horinouchi, Yuki Hitomi, Akemi Shono, Seik-Soon Khor, Yosuke Omae, Kaname Kojima, et al. "Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population." Journal of the American Society of Nephrology 29, no. 8 (July 16, 2018): 2189–99. http://dx.doi.org/10.1681/asn.2017080859.
Full textAbstract:
Background Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown.Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes (HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1) was conducted on the basis of Japanese-specific references. We performed genotyping for HLA-DRB1/-DQB1 using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay.Results The most significant association was detected in the HLA-DR/DQ region and replicated (rs4642516 [minor allele G], combined Pallelic=7.84×10−23; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to 0.41; rs3134996 [minor allele A], combined Pallelic=1.72×10−25; OR, 0.29; 95% CI, 0.23 to 0.37). HLA-DRB1*08:02 (Pc=1.82×10−9; OR, 2.62; 95% CI, 1.94 to 3.54) and HLA-DQB1*06:04 (Pc=2.09×10−12; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary HLA alleles associated with childhood SSNS. HLA-DRB1*08:02-DQB1*03:02 (Pc=7.01×10−11; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor.Conclusions The most significant association with childhood SSNS was detected in the HLA-DR/DQ region. Further HLA allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.
34
Penova, Marina, Shuji Kawaguchi, Jun-ichirou Yasunaga, Takahisa Kawaguchi, Tomoo Sato, Meiko Takahashi, Masakazu Shimizu, et al. "Genome wide association study of HTLV-1–associated myelopathy/tropical spastic paraparesis in the Japanese population." Proceedings of the National Academy of Sciences 118, no. 11 (March 1, 2021): e2004199118. http://dx.doi.org/10.1073/pnas.2004199118.
Full textAbstract:
HTLV-1–associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I (P = 1.54 × 10−9) and class II (P = 1.21 × 10−8) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C*07:02 (P = 2.61 × 10−5), HLA-B*07:02 (P = 4.97 × 10−10), HLA-DRB1*01:01 (P = 1.15 × 10−9) and HLA-DQB1*05:01 (P = 2.30 × 10−9) were associated with disease risk, while HLA-B*40:06 (P = 3.03 × 10−5), HLA-DRB1*15:01 (P = 1.06 × 10−5) and HLA-DQB1*06:02 (P = 1.78 × 10−6) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP (P = 9.52 × 10−10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.
35
Gasperi, Christiane, Till F. M. Andlauer, Ana Keating, Benjamin Knier, Ana Klein, Verena Pernpeintner, Peter Lichtner, et al. "Genetic determinants of the humoral immune response in MS." Neurology - Neuroimmunology Neuroinflammation 7, no. 5 (July 16, 2020): e827. http://dx.doi.org/10.1212/nxi.0000000000000827.
Full textAbstract:
ObjectiveIn this observational study, we investigated the impact of genetic factors at the immunoglobulin heavy chain constant locus on chromosome 14 and the major histocompatibility complex region on intrathecal immunoglobulin G, A, and M levels as well as on B cells and plasmablasts in the CSF and blood of patients with multiple sclerosis (MS).MethodsUsing regression analyses, we tested genetic variants on chromosome 14 and imputed human leukocyte antigen (HLA) alleles for associations with intrathecal immunoglobulins in 1,279 patients with MS or clinically isolated syndrome and with blood and CSF B cells and plasmablasts in 301 and 348 patients, respectively.ResultsThe minor alleles of variants on chromosome 14 were associated with higher intrathecal immunoglobulin G levels (β = 0.58 [0.47 to 0.68], lowest adjusted p = 2.32 × 10−23), and lower intrathecal immunoglobulin M (β = −0.56 [−0.67 to −0.46], p = 2.06 × 10−24) and A (β = −0.42 [−0.54 to −0.31], p = 7.48 × 10−11) levels. Alleles from the HLA-B*07:02-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype were associated with higher (lowest p = 2.14 × 10−7) and HLA-B*44:02 with lower (β = −0.35 [−0.54 to −0.17], p = 1.38 × 10−2) immunoglobulin G levels. Of interest, different HLA alleles were associated with lower intrathecal immunoglobulin M (HLA-C*02:02, β = −0.45 [−0.61 to −0.28], p = 1.01 × 10−5) and higher immunoglobulin A levels (HLA-DQA1*01:03-DQB1*06:03-DRB1*13:01 haplotype, β = 0.40 [0.21 to 0.60], p = 4.46 × 10−3). The impact of HLA alleles on intrathecal immunoglobulin G and M levels could mostly be explained by associations with CSF B cells and plasmablasts.ConclusionAlthough some HLA alleles seem to primarily drive the extent of humoral immune responses in the CNS by increasing CSF B cells and plasmablasts, genetic variants at the immunoglobulin heavy chain constant locus might regulate intrathecal immunoglobulins levels via different mechanisms.
36
Shaker, Olfat, Heba Bassiony, Maissa El Raziky, Samer S. El-Kamary, Gamal Esmat, Akmal M. El-Ghor, and Mona M. Mohamed. "Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1) as Predictors for Response to Interferon Therapy in HCV Genotype 4." Mediators of Inflammation 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/392746.
Full textAbstract:
Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66%) of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1*0313 allele and DRB1*04-DRB1*11, DQB1*0204-DQB1*0313, DQB1*0309-DQB1*0313, and DQB1*0313-DQB1*0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1*02, DQB1*06, DRB1*13, and DRB1*15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1*1301, DRB1*1361, and DRB1*1369 alleles and DRB1*1301-DRB1*1328, DRB1*1301-DRB1*1361, DRB1*1301-DRB1*1369, DRB1*1328-DRB1*1361, and DRB1*1328-DRB1*1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.
37
Goodin, Douglas S., Jorge R. Oksenberg, Venceslas Douillard, Pierre-Antoine Gourraud, and Nicolas Vince. "Genetic susceptibility to multiple sclerosis in African Americans." PLOS ONE 16, no. 8 (August 9, 2021): e0254945. http://dx.doi.org/10.1371/journal.pone.0254945.
Full textAbstract:
Objective To explore the nature of genetic-susceptibility to multiple sclerosis (MS) in African-Americans. Background Recently, the number of genetic-associations with MS has exploded although the MS-associations of specific haplotypes within the major histocompatibility complex (MHC) have been known for decades. For example, the haplotypes HLA-DRB1*15:01~HLA-DQB1*06:02, and HLA-DRB1*03:01~ HLA-DQB1*02:01 have odds ratios (ORs) for an MS-association orders of magnitude stronger than many of these newly-discovered associations. Nevertheless, all these haplotypes are part of much larger conserved extended haplotypes (CEHs), which span both the Class I and Class II MHC regions. African-Americans are at greater risk of developing MS compared to a native Africans but at lesser risk compared to Europeans. It is the purpose of this manuscript to explore the relationship between MS-susceptibility and the CEH make-up of our African-American cohort. Design/methods The African-American (AA) cohort consisted of 1,305 patients with MS and 1,155 controls, who self-identified as being African-American. For comparison, we used the 18,492 controls and 11,144 MS-cases from the predominantly European Wellcome Trust Case Control Consortium (WTCCC) and the 28,557 phased native Africans from the multinational “Be the Match” registry. The WTCCC and the African-Americans were phased at each of five HLA loci (HLA-A, HLA-C, HLA-B, HLA-DRB1 and HLA-DQB1) and the at 11 SNPs (10 of which were in non-coding regions) surrounding the Class II region of the DRB1 gene using previously-published probabilistic phasing algorithms. Results Of the 32 most frequent CEHs, 18 (56%) occurred either more frequently or exclusively in Africans) whereas 9 (28%) occurred more frequently or exclusively in Europeans. The remaining 5 CEHs occurred in neither control group although, likely, these were African in origin. Eight of these CEHs carried the DRB1*15:03~DQB1*06:02~a36 haplotype and three carried the DRB1*15:01~DQB1*06:02~a1 haplotype. In African Americans, a single-copy of the European CEH (03:01_07:02_07:02_15:01_06:02_a1) was associated with considerable MS-risk (OR = 3.30; p = 0.0001)–similar to that observed in the WTCCC (OR = 3.25; p<10−168). By contrast, the MS-risk for the European CEH (02:01_07:02_07:02_15:01_06:02_a1) was less (OR = 1.49; ns)–again, similar to the WTCCC (OR = 2.2; p<10−38). Moreover, four African haplotypes were “protective” relative to a neutral reference, to three European CEHs, and also to the five other African CEHs. Conclusions The common CEHs in African Americans are divisible into those that are either African or European in origin, which are derived without modification from their source population. European CEHs, linked to MS-risk, in general, had similar impacts in African-Americans as they did in Europeans. By contrast, African CEHs had mixed MS-risks. For a few, the MS-risk exceeded that in a neutral-reference group whereas, for many others, these CEHs were “protective”–perhaps providing a partial rationale for the lower MS-risk in African-Americans compared to European-Americans.
38
Jacobi, Thomas, Lucas Massier, Nora Klöting, Katrin Horn, Alexander Schuch, Peter Ahnert, Christoph Engel, et al. "HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non–Insulin-Treated Type 2 Diabetes." Journal of Clinical Endocrinology & Metabolism 105, no. 3 (January 24, 2020): e245-e254. http://dx.doi.org/10.1210/clinem/dgaa027.
Full textAbstract:
Abstract Context Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. Objectives and Design Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. Results In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non–insulin-treated diabetes (OR 1.37; P = 0.002). Conclusions Genetic variation in the HLA class II locus exerts risk and protective effects on non–insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.
39
Kuzmich, Elena V., Alexander L. Alyanskiy, Svetlana S. Tyapushkina, Anna A. Nasredinova, Natalya E. Ivanova, Ludmila S. Zubarovskaya, and Boris V. Afanasyev. "Identification of the new HLA-B*44:02:45, DQB1*02:85, DQB1*06:210, DRB1*01:01:30 alleles by monoallelic Sanger sequencing." Cellular Therapy and Transplantation 7, no. 1 (March 25, 2018): 62–66. http://dx.doi.org/10.18620/ctt-1866-8836-2018-7-1-62-66.
Full text
40
Dittmar, Manuela, Maximilian Ide, Michael Wurm, and George J. Kahaly. "Early onset of polyglandular failure is associated with HLA-DRB1*03." European Journal of Endocrinology 159, no. 1 (July 2008): 55–60. http://dx.doi.org/10.1530/eje-08-0082.
Full textAbstract:
ObjectivesPolyglandular failure or autoimmunity (PGA) involves at least two endocrine diseases. Several genes may play a role in its etiology. This study analyzed 1) whether HLA-DRB1, HLA-DQB1, and MHC class I chain-related gene A (MICA) polymorphisms are associated in PGA and 2) whether PGA patients display stronger associations with these immune genes than patients with monoglandular autoimmunity (MGA).DesignAssociation study.MethodsHLA-DRB1, HLA-DQB1, and MICA alleles were analyzed in 73 patients with PGA, 283 with MGA, and 206 healthy controls. The HLA-DRB1 and HLA-DQB1 polymorphisms were determined with PCR-amplified DNA being hybridized with PCR-sequence-specific oligonucleotide probes. MICA microsatellites were typed by PCR amplification and fragment size analysis on a DNA sequencer.ResultsHLA-DRB1*03 was strongly increased in patients with PGA (50.7%) versus both controls (21.8%, Pc<0.0001; RR=2.32, 95% CI=1.62–3.33) and MGA (11.4%, Pc<0.0001). HLA-DRB1*03 was highly prevalent in PGA patients with early versus late disease onset (P<0.05, logistic regression analysis). HLA-DRB1*04 allele carriers were more present in PGA versus controls (53.4% vs 22.4%, Pc<0.0001, RR=2.38, 95% CI=1.68–3.38). Further, HLA-DQB1*02 was increased in PGA versus controls (Pc<0.01), whereas HLA-DQB1*06 was decreased (Pc<0.001). Patients with PGA showed more MIC A5.1 and less MIC A6 allele carriers than controls (NS). Presence of the MIC A5.1 allele was not associated with the HLA-DRB1*03 or HLA-DQB1 alleles.ConclusionsHLA-DRB1*03 is a stronger genetic marker in PGA than in MGA, foremost in those with early disease onset.
41
Ndung'u, Thumbi, Simani Gaseitsiwe, Enoch Sepako, Florence Doualla-Bell, Trevor Peter, Soyeon Kim, Ibou Thior, Vladimir A. Novitsky, and Max Essex. "Major Histocompatibility Complex Class II (HLA-DRB and -DQB) Allele Frequencies in Botswana: Association with Human Immunodeficiency Virus Type 1 Infection." Clinical Diagnostic Laboratory Immunology 12, no. 9 (September 2005): 1020–28. http://dx.doi.org/10.1128/cdli.12.9.1020-1028.2005.
Full textAbstract:
ABSTRACT Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Batswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Batswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.
42
Reveille, John D., Xiaodong Zhou, MinJae Lee, Michael H. Weisman, Lin Yi, Lianne S. Gensler, Hejian Zou, et al. "HLA class I and II alleles in susceptibility to ankylosing spondylitis." Annals of the Rheumatic Diseases 78, no. 1 (October 19, 2018): 66–73. http://dx.doi.org/10.1136/annrheumdis-2018-213779.
Full textAbstract:
ObjectiveTo examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry.MethodsHLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses, HLA-B*27-negative patients with AS were analysed separately, and logistic regression and ‘relative predispositional effects’ (RPE) analyses were carried out to control for the major effect of HLA-B*27 on disease susceptibility.ResultsAlthough numerous associations were seen between HLA alleles and AS in whites, among HLA-B*27-negative patients with AS , positive associations were seen with HLA-A*29, B*38, B*49, B*52, DRB1*11 and DPB1*03:01 and negative associations with HLA-B*07, HLA-B*57, HLA-DRB1*15:01, HLA-DQB1*02:01 and HLA-DQB1*06:02. Additional associations with HLA-B*14 and B*40 (B60) were observed via RPE analysis, which excludes the HLA-B*27 alleles. The increased frequency of HLA-B*40:01 and decreased frequency of HLA-B*07 was also seen in Han Chinese and African-Americans with AS. HLA-B*08 was decreased in whites with acute anterior uveitis.ConclusionsThese data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B*27 to be operative in AS predisposition.
43
Campagnuolo, Débora Greice, Rafael Formeton Cita, and Tatiana Elias Colombo. "Frequência dos alelos do sistema antígeno leucocitário humano em doadores e pacientes pré-transplante de medula óssea." Arquivos de Ciências da Saúde 25, no. 1 (April 23, 2018): 71. http://dx.doi.org/10.17696/2318-3691.25.1.2018.853.
Full textAbstract:
Introdução: O estudo da frequência dos alelos detectados nos doadores e pacientes previamente selecionados para o transplante de medula óssea permite estimar as reais chances de um paciente em lista de espera encontrar um doador HLA idêntico não relacionado, além de facilitar e direcionar o planejamento do crescimento do Registro. Objetivo: Descrever e analisar a frequência dos alelos, genótipos e haplótipos HLA de classe I (HLA-A, -B e -C) e classe II (HLA-DRB1 e -DQB1) dos doadores e pacientes pré-transplante de medula óssea, genotipados no laboratório de Imunogenética-HLA do Hospital de Câncer de Barretos. Métodos: Um total de 98 amostras de doadores foram selecionadas com tipificações em alta resolução. As amostras foram tipificadas para os loci HLA-A, -B, -C, -DR e -DQ. Resultados: O predomínio da raça branca reflete a composição étnica da nossa região estudada. As doenças de base mais comuns que levaram o paciente ao transplante foram a leucemia aguda linfóide (34%) e mielóide (29,2%). Os grupos alélicos mais frequentes nos registros foram A*02, A*24, A*03, A*01, B*35, B*44, C*07, DQB1*03, DQB1*05, DQB1*06, DRB1*01 e DRB1*13. Conclusões: Os resultados encontrados reforçam a importância de conhecer o perfil demográfico e imunogenético das regiões do Brasil, contribuindo desta forma na redução do tempo de espera por um doador histocompatível.
44
KALLWEIT, ULF. "Narkolepsie – Aktuelles zur Pathophysiologie." Schlaf 04, no. 04 (2015): 199–204. http://dx.doi.org/10.1055/s-0038-1626150.
Full textAbstract:
Narkolepsie ist eine seltene neurologische Erkrankung mit den Hauptsymptomen Tagesschläfrigkeit und Kataplexie. Es wird eine immunvermittelte Pathogenese postuliert, bei der sowohl genetische Faktoren (HLA-DQB1*06:02) wie auch Umweltfaktoren (Streptokokken, H1N1-Virus bzw. -Impfung) von Bedeutung sind und an deren Ende der Untergang von Hypokretin-produzierenden Zellen im Hypothalamus steht. Die aktuellen neuroimmunologischen Erkenntnisse helfen bei der Entwicklung innovativer therapeutischer Strategien.
45
Ramilyeva, I. R., Zh K. Burkitbaev, S. A. Abdrakhmanova, A. A. Turganbekova, D. K. Baimukasheva, and E. B. Zhiburt. "DISTRIBUTION PATTERN FOR HLA SPECIFICITIES IN THE PATIENTS WITH ACUTE MYELOID LEUKEMIA." Medical Immunology (Russia) 21, no. 5 (December 13, 2019): 965–72. http://dx.doi.org/10.15789/1563-0625-2019-5-965-972.
Full textAbstract:
The article presents a study on the distribution of gene polymorphisms in the histocompatibility antigens among the patients diagnosed with AML, and healthy donors in the Republic of Kazakhstan, as well as features of the HLA-A*, *B, Cw*, DRB1*, DQB1* distribution among the patients with acute myeloid leukemia (AML). HLA typing and data processing were performed at the Research and Production Center of Transfusiology, Nur-Sultan. A total of 3808 people were examined, including 3621 healthy blood donors and 187 patients diagnosed with AML. Genomic DNA for HLA typing was isolated from peripheral blood leukocytes by proteinase method using columns with silica membrane and using a set of reagents PROTRANS DNA BOX (Protrans, Germany). Typing of HLA-A, B, C, DRB1, DQB1 in the patients and blood donors was performed by polymerase chain reaction using commercial reagent kits from Protrans (PROTRANS HLA- A*/B*/DRB1* Cyclerplate System, PROTRANS HLA-C* Cyclerplate System, PROTRANS HLA-DQB1* Cyclerplate System).HLA-A*31 (OR = 1.8; CI 1.16-2.79; p < 0.01) proved to be more common in the group of patients compared to the control group, which suggesting an association between AML and presence of this antigen. The control group showed an increased frequency of HLA-A*02 antigen (OR = 0.55; CI 0.41-0.75; p < 0.01). This antigen may be, therefore, exert a protective effect in AML development.The studies of major histocompatibility complex which include HLA genes, did significantly expanded the understanding of HLA antigens which may have strong associative links with distinct diseases, and moderately or poorly expressed links in other disorders. Analysis of the literature data showed that myeloid leukemia is characterized by decreased frequency of HLA-B13, B14, B40 antigens, most often determined by antigens B16, Bw 22, B27. In this study, HLA-A*31, B*37 were associated with AML. Phenotypes with antigens HLA-A*02, B*27, C*02, DRB1*01, *04, DQB1*06 have a probable protective effect on the development of this pathology.The study has determined some features of histocompatibility gene distribution in AML patients, detection of HLA-markers that determine the risk or resistance to the occurrence of this disease. We have established characteristic specific markers of HLA system among AML patients in Kazakhstan, which may be associated with higher risk of the disease.
46
Futenma, Kunihiro, Yoshikazu Takaesu, Masaki Nakamura, Kenichi Hayashida, Noboru Takeuchi, and Yuichi Inoue. "Metabolic-Syndrome-Related Comorbidities in Narcolepsy Spectrum Disorders: A Preliminary Cross-Sectional Study in Japan." International Journal of Environmental Research and Public Health 19, no. 10 (May 22, 2022): 6285. http://dx.doi.org/10.3390/ijerph19106285.
Full textAbstract:
Narcolepsy types 1 (NT1) and 2 (NT2) and idiopathic hypersomnia (IH) are thought to be a disease continuum known as narcolepsy spectrum disorders (NSDs). This study aimed to assess the prevalence of and factors associated with metabolic-syndrome-related disorders (MRDs) among patients with NSD. Japanese patients with NSD (NT1, n = 94; NT2, n = 83; and IH, n = 57) aged ≥35 years were enrolled in this cross-sectional study. MRD was defined as having at least one of the following conditions: hypertension, diabetes, or dyslipidemia. Demographic variables and MRD incidence were compared among patients in the respective NSD categories. Multivariate logistic regression analysis was used to investigate the factors associated with MRDs. Patients with NT1 had a higher body mass index (BMI) and incidence of MRD than that had by those with NT2 or IH. Age, BMI, and the presence of OSA were significantly associated with the incidence of MRD in NSDs. Age and BMI in NT1, BMI and human leukocyte antigen (HLA)-DQB1*06:02 positivity in NT2, and only age in IH were factors associated with the incidence of MRD. Obesity should be carefully monitored in narcolepsy; however, NT2 with HLA-DQB1*06:02 positive should be followed up for the development of MRD even without obesity.
47
Satoko, Morishima, Koichi Kashiwase, Fumihiro Azuma, Toshio Yabe, Aiko Sato-Otsubo, Seishi Ogawa, Takashi Shiina, et al. "Impact Of HLA Allele and Haplotype On Acute Graft-Versus-Host Disease and Survival After Hematopoietic Stem Cell Transplantation From Unrelated Donor." Blood 122, no. 21 (November 15, 2013): 708. http://dx.doi.org/10.1182/blood.v122.21.708.708.
Full textAbstract:
Abstract Background Although the effect of allele matching of each HLA locus on the clinical outcome of unrelated hematopoietic stem cell transplantation (UR-HSCT) has been characterized, the effect of HLA allele or haplotype (HP) itself has not been well elucidated. The HLA region is recognized as one of the most important genetic regions associated with human disease, especially autoimmune and infectious diseases. We therefore hypothesized that the immunological response and the clinical outcome following UR-HSCT depend not only on HLA allele matching but also on the HLA allele itself or HLA-linked genetic background of the patient and donor. Methods We analyzed 5237 patients who received T-cell-replete bone marrow transplants from serologically HLA-A, -B, and -DR antigen-matched unrelated donors facilitated by the Japan Marrow Donor Program between 1993 and 2008. HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were retrospectively genotyped. HLA allele frequencies were calculated by direct counting, and multi-locus HLA HP frequencies were estimated using the maximum-likelihood method with EM algorithm of PyPop software. Patients were stratified by HLA-matching status into a full match (FM) group (12/12-matched, n=733) and a mismatch (MM) group (≤11/12-matched, n=4504). The effect of HLA alleles or HPs with a frequency greater than 5% on acute graft-versus-host disease (aGVHD) and overall survival (OS) was analyzed using a multivariate competing risk regression model. The results are expressed as hazard ratios (HRs) comparing specific allele/haplotype-positive group to -negative group. Results For each allele, the number of HLA alleles significantly associated with aGVHD (p <.01) in the MM group, were as follows: HLA-A (1 of 10), HLA-B (2 of 17), HLA-C (3 of 15), HLA-DRB1 (1 of 17), HLA-DQB1 (1 of 11) and HLA-DPB1 (0 of 10). In contrast, only one HLA-DPB1 allele was significantly associated with aGVHD in the FM group. The following patient and donor HLA alleles were significantly associated with a reduced risk of aGVHD in the MM group: HLA-A*33:03, C*14:03, B*44:03, DRB1*13:02, and DQB1*06:04. These alleles are located on a common HP (HP-P2) in the Japanese population, which showed a similar effect on grade II-IV (n=534; HR 0.79; p=.001) and III-IV (HR 0.70; p=.004) aGVHD. Strong linkage disequilibrium (LD) hampered determination of the allele responsible for the reducing risk of aGVHD. A significant association with an increased risk of grade III-IV aGVHD and a poor OS was observed in patient HLA-B*51:01 (n=756; aGVHD: HR 1.51, p<.001; OS: HR 1.19, p=.003, respectively) and donor HLA-B*51:01 (n=773; HR 1.46, p<.001; HR 1.15, p=.015) , patient HLA-C*14:02 (n=599; HR 1.55, p<.001; HR 1.19, p=.007), and donor HLA-C*15:02 (n=226; HR 1.62, p<.001; HR 1.38, p=.001) in the MM group. HLA-B*51:01 demonstrated strong positive LD with HLA-C*14:02 and -C*15:02. A significant association with an increased risk of grade III-IV aGVHD and a poor OS was also observed in patient HLA-C*14:02-B*51:01 (n=586; HR 1.52, p<.001; HR 1.19; p=.007) and donor HLA-C*15:02-B*51:01 (n=106; HR 1.98, p<.001; HR 1.53, p=.001). HLA-DPB1*04:02 was the only allele associated with an increased risk of grade II-IV aGVHD in the FM group (n=173; HR 1.64; p=.001). HLA-DPB1*04:02 was linked to two distinctive extended HPs, and the effect of these HPs on aGVHD was stronger in the patients with HLA-DRB1*04:05-DQB1*04:01-DPB1*04:02 (n=60; HR 2.15; p<.001) than in those with HLA-DRB1*01:01-DQB1*05:01-DPB1*-DPB1*04:02 (n=125; HR 1.40; p=.035). HLA-DRB1*04:05-DQB1*04:01-DPB1*04:02 was also significantly associated with poor OS in the FM group (HR 1.65; p=.01). HP-P2 showed a tendency to reduce the risk of grade II-IV aGVHD in the FM group (n=119; HR 0.70; p=.075). Conclusion Patient- and donor-specific HLA alleles and HPs themselves contribute to the risk of aGVHD and survival after UR-HSCT. In addition to HLA-B*51:01 being strongly associated with Bechet’s disease, we found this allele to be associated with an increased risk of aGVHD in UR-HSCT. Given that different HLA alleles and HPs were identified in the FM and MM groups, multiple mechanisms, including HLA-mismatch induced alloreactivity, might be involved in the development or exacerbation of aGVHD. These findings suggest that, in addition to HLA-matching status, consideration of patient and donor HLA alleles and haplotypes will provide predictive risk factors for UR-HSCT. Disclosures: No relevant conflicts of interest to declare.
48
Beecham, Ashley H., Lilyana Amezcua, Angel Chinea, Clara P. Manrique, Lissette Gomez, Andrea Martinez, Gary W. Beecham, et al. "Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population." PLOS ONE 17, no. 12 (December 22, 2022): e0279132. http://dx.doi.org/10.1371/journal.pone.0279132.
Full textAbstract:
The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency differences and population-specific risk alleles identified. We sought to identify MHC-specific MS susceptibility variants and assess the effect of ancestral risk modification within 2652 Latinx and Hispanic individuals as well as 2435 Black and African American individuals. We have identified several novel susceptibility alleles which are rare in European populations including HLA-B*53:01, and we have utilized the differing linkage disequilibrium patterns inherent to these populations to identify an independent role for HLA-DRB1*15:01 and HLA-DQB1*06:02 on MS risk. We found a decrease in Native American ancestry in MS cases vs controls across the MHC, peaking near the previously identified MICB locus with a decrease of ~5.5% in Hispanics and ~0.4% in African Americans. We have identified several susceptibility variants, including within the MICB gene region, which show global ancestry risk modification and indicate ancestral differences which may be due in part to correlated environmental factors. We have also identified several susceptibility variants for which MS risk is modified by local ancestry and indicate true ancestral genetic differences; including HLA-DQB1*06:02 for which MS risk for European allele carriers is almost two times the risk for African allele carriers. These results validate the importance of investigating MS susceptibility at an ancestral level and offer insight into the epidemiology of MS phenotypic diversity.
49
Simmons, Kimber M., Angela M. Mitchell, Aimon A. Alkanani, Kristen A. McDaniel, Erin E. Baschal, Taylor Armstrong, Laura Pyle, Liping Yu, and Aaron W. Michels. "Failed Genetic Protection: Type 1 Diabetes in the Presence of HLA-DQB1*06:02." Diabetes 69, no. 8 (May 21, 2020): 1763–69. http://dx.doi.org/10.2337/db20-0038.
Full text
50
Yang, Kuo‐Liang, Yuan‐Bin Yu, Shih‐Chiang Lin, and Py‐Yu Lin. "Detection of the HLA‐DQB1*06:02:43 allele in a Taiwanese leukemic patient." HLA 98, no. 4 (April 25, 2021): 412–14. http://dx.doi.org/10.1111/tan.14276.
Full text