Log in

Relevant bibliographies by topics / INTERFERONOPATIA / Journal articles

Journal articles on the topic 'INTERFERONOPATIA'

To see the other types of publications on this topic, follow the link: INTERFERONOPATIA.

Author: Grafiati

Published: 1 April 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'INTERFERONOPATIA.'

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

Souza, Victória Cabral de, Roberto de Barros Silva, and Caique Antunis. "INTERFERON-I COMO ALVO TERAPÊUTICO NO TRATAMENTO DO LÚPUS ERITEMATOSO SISTÊMICO: USO DOS ANTICORPOS MONOCLONAIS ANIFROLUMABE, RONTALIZUMABE E SIFALIMUMABE." Revista Ibero-Americana de Humanidades, Ciências e Educação 9, no. 1 (January 31, 2023): 717–31. http://dx.doi.org/10.51891/rease.v9i1.8303.

Full text

Abstract:

O lúpus eritematoso sistêmico (LES) é uma doença crônica de origem autoimune, caráter sistêmico e multifatorial que possui uma maior prevalência entre as mulheres em idade fértil, mas que pode se manifestar durante a infância e também acometer indivíduos do sexo masculino. No LES, é possível observar uma desregulação do sistema imunológico através da perda da tolerância aos antígenos do próprio corpo e produção de auto-anticorpos que se depositam nos tecidos, podendo afetar diversos sistemas corporais. Citocinas como o interferon-I apresentam um papel central na patogênese do LES, pois apresentam um papel-chave da modulação da inflamação a nível sistêmico e dano tecidual local. Objetivo: avaliar sistematicamente o desfecho de pacientes com lúpus ativo submetidos ao tratamento com anticorpos monoclonais anti interferon I, como o anifrolumabe, rontalizumabe sifalimumabe. Metodologia: Foi realizada uma revisão sistemática de literatura através da busca por artigos científicos indexados em bancos de dados como PubMed e MedLine publicados entre os anos de 2012 e 2022. Cerca de 176 artigos foram considerados inicialmente, mas, após a aplicação dos critérios de elegibilidade, somente 8 artigos foram incluídos nesta revisão. Resultados e discussão: O uso de antagonistas e neutralizadores de interferon I promovem um bloqueio significativo da interferonopatia do tipo I em pacientes lúpicos, todavia, o seu uso está associado a uma maior incidência de eventos adversos, como maior suscetibilidade a infecções virais, como influenza e hérpes-zóster. Conclusão: A presente revisão demonstra que embora o interferon I possua um papel importante na patogênese do lúpus, é imprescindível analisar os possíveis riscos e benefícios do uso das terapias biológicas anti interferon I, analisando o histórico de doenças virais e presença de infecções agudas, uma vez que os pacientes lúpicos estão mais suscetíveis a infecções oportunistas e o interferon I apresenta um papel fundamental na supressão da replicação viral.

APA, Harvard, Vancouver, ISO, and other styles

2

Tommasini, Alberto, Irene Bruno, Maria Elisa Morelli, and Loredana Lepore. "Le interferonopatie di tipo I." Medico e Bambino 40, no. 8 (September 23, 2021): 509–14. http://dx.doi.org/10.53126/meb40509.

Full text

Abstract:

Type I interferonopathies are autoinflammatory monogenic disorders arising from excessive production of interferons. Some manifestations like chilblains, neurologic involvement, arthritis and lipodystrophy may be shared by several diseases. Measure of interferon score and genetic analysis can assist a definite diagnosis. Among immunomodulant drugs, glucocorticoids, micofenolate and antimalarials can be of some benefit, however other drugs like JAK inhibitors seem more effective in controlling interferon-related complaints. Apart from allowing better diagnosis and care to affected patients, the study of interferonopathies may also reflect on a better knowledge on multifactorial disorders associated with interferon-related inflammation.

APA, Harvard, Vancouver, ISO, and other styles

3

Payet, Cloé A., Axel You, Odessa-Maud Fayet, Nadine Dragin, Sonia Berrih-Aknin, and Rozen Le Panse. "Myasthenia Gravis: An Acquired Interferonopathy?" Cells 11, no. 7 (April 4, 2022): 1218. http://dx.doi.org/10.3390/cells11071218.

Full text

Abstract:

Myasthenia gravis (MG) is a rare autoimmune disease mediated by antibodies against components of the neuromuscular junction, particularly the acetylcholine receptor (AChR). The thymus plays a primary role in AChR-MG patients. In early-onset AChR-MG and thymoma-associated MG, an interferon type I (IFN-I) signature is clearly detected in the thymus. The origin of this chronic IFN-I expression in the thymus is not yet defined. IFN-I subtypes are normally produced in response to viral infection. However, genetic diseases called interferonopathies are associated with an aberrant chronic production of IFN-I defined as sterile inflammation. Some systemic autoimmune diseases also share common features with interferonopathies. This review aims to analyze the pathogenic role of IFN-I in these diseases as compared to AChR-MG in order to determine if AChR-MG could be an acquired interferonopathy.

APA, Harvard, Vancouver, ISO, and other styles

4

Briggs, Tracy A., Anindita Paul, Gillian Rice, and Ariane L. Herrick. "RNASEH2B Related Adult-Onset Interferonopathy." Journal of Clinical Immunology 39, no. 6 (July 31, 2019): 620–22. http://dx.doi.org/10.1007/s10875-019-00673-w.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Rodero, Mathieu P., Marie-Louise Frémond, Gillian I. Rice, Bénédicte Neven, and Yanick J. Crow. "JAK inhibition in STING-associated interferonopathy." Annals of the Rheumatic Diseases 75, no. 12 (October 12, 2016): e75-e75. http://dx.doi.org/10.1136/annrheumdis-2016-210504.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Manoussakis, Menelaos N., Clio P. Mavragani, Adrianos Nezos, Evangelia Zampeli, Anastassios Germenis, and Haralampos M. Moutsopoulos. "Type I interferonopathy in a young adult." Rheumatology 56, no. 12 (August 14, 2017): 2241–43. http://dx.doi.org/10.1093/rheumatology/kex316.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Krieger, Ben Zion, Theresa Calvelli, Anna Kadish, and Arye Rubinstein. "1042 INTERFERONOPATHY IN THE BARE LYMPHOCYTE SYNDROME." Pediatric Research 19, no. 4 (April 1985): 284A. http://dx.doi.org/10.1203/00006450-198504000-01072.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Piotto, Daniela Gerent Petry, Kátia Tomie Kozu, and Sandro Félix Perazzio. "Quando suspeitar de doenças autoinflamatórias na infância?" Reumatologia Pediátrica, no. 2021 jan-mar;20(1) (March 31, 2021): 16–26. http://dx.doi.org/10.46833/reumatologiasp.2021.20.1.16-26.

Full text

Abstract:

Resumo: cerca de 30% dos erros inatos da imunidade apresentam fenótipo clínico resultante da quebra da imunorregulação, clinicamente manifesto por autoimunidade, autoinflamação, linfoproliferação, neoplasias e atopia grave: as chamadas doenças imunorreguladoras primárias. As doenças autoinflamatórias (DAI) representam uma parte significativa desse grupo e são causadas pela ativação desenfreada do inflamassomo e do NF-κB, culminando com a produção excessiva de IL-1β. Clinicamente, as DAI se manifestam por processos inflamatórios sistêmicos aparentemente sem causa, episódicos ou persistentes e na ausência de evidência de altos títulos de autoanticorpos ou linfócitos T autorreativos. A classificação das DAI pode ser baseada na fisiopatologia em inflamassomopatias, relopatias e interferonopatias, ou centrada nos aspectos clínicos em DAI febris periódicas, doenças piogênicas assépticas cutâneas e ósseas. O diagnóstico deve levar em consideração o tripé: fenótipo clínico, marcadores inflamatórios e achados genéticos. Entretanto, a ausência de variantes genéticas (40-60% das DAI) na presença de fenótipo clínico autoinflamatório inconteste não exclui o diagnóstico, sendo esses casos denominados DAI indefinidas ou indeterminadas. De maneira geral, as terapias com colchicina, bloqueio da IL-1β, do TNFα e da IL-6 são eficazes nas DAI febris periódicas e nas piogênicas estéreis. As interferonopatias tendem a responder ao uso de inibidores de Jak (tofacitinibe, ruxolitinibe e baricitinibe) e ao bloqueio do receptor de IFN-I (anifrolumabe). Unitermos: Doenças autoinflamatórias. Doenças imunorreguladoras primárias. Imunidade inata. Inflamassomo, NF-κB.

APA, Harvard, Vancouver, ISO, and other styles

9

Crow, Yanick, Nandaki Keshavan, Jacques Patrick Barbet, Geanina Bercu, Vincent Bondet, Charlotte Boussard, Nathalie Dedieu, et al. "Cardiac valve involvement in ADAR-related type I interferonopathy." Journal of Medical Genetics 57, no. 7 (November 26, 2019): 475–78. http://dx.doi.org/10.1136/jmedgenet-2019-106457.

Full text

Abstract:

BackgroundAdenosine deaminases acting on RNA (ADAR) mutations cause a spectrum of neurological phenotypes ranging from severe encephalopathy (Aicardi-Goutières syndrome) to isolated spastic paraplegia and are associated with enhanced type I interferon signalling. In children, non-neurological involvement in the type I interferonopathies includes autoimmune and rheumatological phenomena, with calcifying cardiac valve disease only previously reported in the context of MDA5 gain-of-function.ResultsWe describe three patients with biallelic ADAR mutations who developed calcifying cardiac valvular disease in late childhood (9.5–14 years). Echocardiography revealed progressive calcification of the valvular leaflets resulting in valvular stenosis and incompetence. Two patients became symptomatic with biventricular failure after 5–6.5 years. In one case, disease progressed to severe cardiac failure despite maximal medical management, with death occurring at 17 years. Another child received mechanical mitral and aortic valve replacement at 16 years with good postoperative outcome. Histological examination of the affected valves showed fibrosis and calcification.ConclusionsType I interferonopathies of differing genetic aetiology demonstrate an overlapping phenotypic spectrum which includes calcifying cardiac valvular disease. Individuals with ADAR-related type I interferonopathy may develop childhood-onset multivalvular stenosis and incompetence which can progress insidiously to symptomatic, and ultimately fatal, cardiac failure. Regular surveillance echocardiograms are recommended to detect valvular disease early.

APA, Harvard, Vancouver, ISO, and other styles

10

Kozlova, A. L., E. S. Romanenko, V. I. Burlakov, E. V. Deripapa, Sv P. Khomyakova, A. N. Remizov, G. V. Tereshenko, and A. Yu Shcherbina. "CLINICAL CASE OF TYPE I INTERFERONOPATHY: AICARDI–GOUTIERES SYNDROME." Pediatria. Journal named after G.N. Speransky 98, no. 3 (June 10, 2019): 257–65. http://dx.doi.org/10.24110/0031-403x-2019-98-3-257-265.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Manzano, Giovanna S., Jared K. Woods, and Anthony A. Amato. "Covid-19–Associated Myopathy Caused by Type I Interferonopathy." New England Journal of Medicine 383, no. 24 (December 10, 2020): 2389–90. http://dx.doi.org/10.1056/nejmc2031085.

Full text

APA, Harvard, Vancouver, ISO, and other styles

12

Crow, Yanick J., and Jean-Laurent Casanova. "STING-Associated Vasculopathy with Onset in Infancy — A New Interferonopathy." New England Journal of Medicine 371, no. 6 (August 7, 2014): 568–71. http://dx.doi.org/10.1056/nejme1407246.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Tüngler, Victoria, Nadja König, Claudia Günther, Kerstin Engel, Christoph Fiehn, Martin Smitka, Maja von der Hagen, Reinhard Berner, and Min Ae Lee-Kirsch. "Response to: ‘JAK inhibition in STING-associated interferonopathy’ by Crowet al." Annals of the Rheumatic Diseases 75, no. 12 (November 3, 2016): e76-e76. http://dx.doi.org/10.1136/annrheumdis-2016-210565.

Full text

APA, Harvard, Vancouver, ISO, and other styles

14

Picard, Cécile, Guillaume Thouvenin, Caroline Kannengiesser, Jean-Christophe Dubus, Nadia Jeremiah, Frédéric Rieux-Laucat, Bruno Crestani, et al. "Severe Pulmonary Fibrosis as the First Manifestation of Interferonopathy (TMEM173 Mutation)." Chest 150, no. 3 (September 2016): e65-e71. http://dx.doi.org/10.1016/j.chest.2016.02.682.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Goldmann, Tobias, Nicolas Zeller, Jenni Raasch, Katrin Kierdorf, Kathrin Frenzel, Lars Ketscher, Anja Basters, et al. "USP 18 lack in microglia causes destructive interferonopathy of the mouse brain." EMBO Journal 34, no. 12 (April 20, 2015): 1612–29. http://dx.doi.org/10.15252/embj.201490791.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Rafat, Cédric, and Alice Doreille. "Could Plasmodium falciparum–related kidney disease stand as another example of interferonopathy?" Kidney International 102, no. 3 (September 2022): 669–70. http://dx.doi.org/10.1016/j.kint.2022.06.009.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Kozlova, А. L., М. Е. Leonteva, V. I. Burlakov, Z. А. Nesterenko, О. М. Laba, М. V. Pisareva, N. Yu Kan, et al. "Clinical case of type I interferonopathy: homozygous STAT2 gain-of-function mutation." Pediatric Hematology/Oncology and Immunopathology 20, no. 3 (October 8, 2021): 132–39. http://dx.doi.org/10.24287/1726-1708-2021-20-3-132-139.

Full text

Abstract:

The article is devoted to an extremely rare variant of type I interferonopathies associated with a homozygous gain of function (GOF) mutation in the STAT2 gene in a 5-year-old child. This genetic defect was first described in 2019, and so far only 3 cases are known in the world with a similar pathology. Here we present the fourth clinical case and our experience in managing a patient with STAT2 GOF. The article presents the key aspects of the pathogenesis, clinical picture based on the analysis of all known cases of the disease. The absence of established criteria and methods of treatment for this disease is due to the rarity and relative novelty of the described nosology. We present the experience of treatment using a JAK kinase inhibitor, followed by an assessment of the effectiveness of the therapy and side effects. The patient's parents agreed to use the information, including the child's photo, in scientific research and publications.

APA, Harvard, Vancouver, ISO, and other styles

18

Frémond, M.-L., C. Gitiaux, D. Bonnet, T. Guiddir, Y. Crow, L. de Ponthual, and B. Bader-Meunier. "Mosaic tetrasomy 9p: a mendelian interferonopathy associated with pediatric-onset overlap myositis." Pediatric Rheumatology 13, Suppl 1 (2015): P140. http://dx.doi.org/10.1186/1546-0096-13-s1-p140.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Meuwissen, Marije E. C., Rachel Schot, Sofija Buta, Grétel Oudesluijs, Sigrid Tinschert, Scott D. Speer, Zhi Li, et al. "Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome." Journal of Experimental Medicine 213, no. 7 (June 20, 2016): 1163–74. http://dx.doi.org/10.1084/jem.20151529.

Full text

Abstract:

Pseudo-TORCH syndrome (PTS) is characterized by microcephaly, enlarged ventricles, cerebral calcification, and, occasionally, by systemic features at birth resembling the sequelae of congenital infection but in the absence of an infectious agent. Genetic defects resulting in activation of type 1 interferon (IFN) responses have been documented to cause Aicardi-Goutières syndrome, which is a cause of PTS. Ubiquitin-specific peptidase 18 (USP18) is a key negative regulator of type I IFN signaling. In this study, we identified loss-of-function recessive mutations of USP18 in five PTS patients from two unrelated families. Ex vivo brain autopsy material demonstrated innate immune inflammation with calcification and polymicrogyria. In vitro, patient fibroblasts displayed severely enhanced IFN-induced inflammation, which was completely rescued by lentiviral transduction of USP18. These findings add USP18 deficiency to the list of genetic disorders collectively termed type I interferonopathies. Moreover, USP18 deficiency represents the first genetic disorder of PTS caused by dysregulation of the response to type I IFNs. Therapeutically, this places USP18 as a promising target not only for genetic but also acquired IFN-mediated CNS disorders.

APA, Harvard, Vancouver, ISO, and other styles

20

Emralino, Francine Lianne, Saya Satoh, Nobuhiro Sakai, Masamichi Takami, Fumihiko Takeuchi, Nan Yan, Frank Rutsch, Takashi Fujita, and Hiroki Kato. "Double-Stranded RNA Induces Mortality in an MDA5-Mediated Type I Interferonopathy Model." Journal of Immunology 209, no. 11 (December 1, 2022): 2093–103. http://dx.doi.org/10.4049/jimmunol.2200367.

Full text

Abstract:

Abstract Gain-of-function mutations in the viral dsRNA sensor melanoma differentiation–associated protein 5 (MDA5) lead to autoimmune IFNopathies, including Singleton–Merten syndrome (SMS) and Aicardi–Goutières syndrome. However, much remains unclear regarding the mechanism of disease progression and how external factors such as infection or immune stimulation with vaccination can affect the immune response. With this aim, we generated mice with human MDA5 bearing the SMS-associated mutation R822Q (hM-R822Q). hM-R822Q transgenic (Tg) mice developed SMS-like heart fibrosis, aortic valve enlargement, and aortic calcification with a systemic IFN-stimulated gene signature resulting in the activation of the adaptive immune response. Although administration of the viral dsRNA mimic polyinosinic-polycytidylic acid [poly(I:C)] did not have remarkable effects on the cardiac phenotype, dramatic inflammation was observed in the intestines where IFN production was most elevated. Poly(I:C)-injected hM-R822Q Tg mice also developed lethal hypercytokinemia marked by massive IL-6 levels in the serum. Interrupting the IFN signaling through mitochondrial antiviral signaling protein or IFN-α/β receptor alleviated hM-R822Q–induced inflammation. Furthermore, inhibition of JAK signaling with tofacitinib reduced cytokine production and ameliorated mucosal damage, enabling the survival of poly(I:C)-injected hM-R822Q Tg mice. These findings demonstrate that the MDA5 R822Q mutant introduces a critical risk factor for uncontrollable inflammation on viral infection or vaccination.

APA, Harvard, Vancouver, ISO, and other styles

21

Sifuentes-Dominguez, Luis, Petro Starokadomskyy, Jacob Welch, Bhaskar Gurram, Jason Y. Park, Prasad Koduru, and Ezra Burstein. "Mosaic Tetrasomy 9p Associated With Inflammatory Bowel Disease." Journal of Crohn's and Colitis 13, no. 11 (April 25, 2019): 1474–78. http://dx.doi.org/10.1093/ecco-jcc/jjz079.

Full text

Abstract:

Abstract The genetic basis of inflammatory bowel disease remains to be elucidated completely. Here we report on a patient with inflammatory bowel disease who has mosaic tetrasomy of the short arm of chromosome 9, a genomic region that harbours the type I interferon gene cluster. We show that increased interferon activation is present in peripheral blood and intestinal tissue from this patient, similar to previous reports of autoinflammatory organ damage driven by interferon activation in other patients with this chromosomal abnormality. To our knowledge, this is the first case of tetrasomy 9p-associated interferonopathy driving intestinal inflammation and highlights the role that type-I interferon pathways can play in the pathogenesis of intestinal inflammation.

APA, Harvard, Vancouver, ISO, and other styles

22

Komura, Kazuhiro, Yuki Ichimura, Naoko Okiyama, Kazuyoshi Watanabe, Hiroaki Muramoto, and Takashi Matsushita. "Interferon signature in cutaneous lesion of COVID toes." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 20.37. http://dx.doi.org/10.4049/jimmunol.206.supp.20.37.

Full text

Abstract:

Abstract Increasing reports have showed several kinds of dermatological manifestation in Coronavirus disease 2019 (COVID-19). Some of them may occur as a direct implication of coronavirus infection. Within those, acral skin changes, recently called COVID toes, have a potential to provide a diagnostic value. We herein described a 49-year old Japanese man with COVID toes. The skin lesions appeared simultaneously with fever. The rash was similar for cold-induced erythema multiforme of the patients with familial Chilblain; hereditary type I interferonopathy. Histopathological staining indicated up-regulated expression of MxA, effected by local enhancement of type I interferon. These speculated that the specificity of COVID toes may depend on interferon up-regulated by specific mechanisms.

APA, Harvard, Vancouver, ISO, and other styles

23

Hauck, Fabian. "Angeborene autoinflammatorische Störungen der cGAS-STING- und OASRNase-L-vermittelten Nukleinsäure-Immunität." Translationale Immunologie 5, no. 3 (October 28, 2021): 160–65. http://dx.doi.org/10.47184/ti.2021.03.04.

Full text

Abstract:

Typ-I-Interferonopathien sind autoinflammatorische Störungen der angeborenen Nukleinsäure-Immunität, die zusätzlich zu Epitop-spezifischer Autoimmunität prädispositionieren. In der Immunbiologie ist die Nukleinsäure-Immunität vermittelt durch die cGAS-STING- und OAS-RNase-L-Signalwege weitgehend verstanden. In der translationellen und klinischen Immunologie zeigen angeborene Störungen dieser Signalwege deren physiologische Relevanz an der Schnittstelle zwischen Selbst- und Fremd-Nukleinsäure-Erkennung und führen zu einem neuen Verständnis von seit Langem bekannten Krankheitsbildern. Dieser Übersichtsartikel fasst aktuelle pathophysiologische Konzepte und deren klinische Implikationen zur unkontrollierten cGAS- und OAS1-Aktivierung durch biallelische LSM11 und RNU7-1-loss-of-function-, monoallelische ATAD3A dominant-negative und monoallelische OAS1-gain-of-function-Varianten zusammen. Eine murine monoallelische dominante Oas2-Variante wird als Modell für eine mögliche Organ-spezifische humane Typ-I-Interferonopathie diskutiert.

APA, Harvard, Vancouver, ISO, and other styles

24

Okada, Yuri, Rumiko Izumi, Tatsuhiko Hosaka, Satoshi Watanabe, Tomomi Shijo, Naokazu Hatchome, Risa Konishi, et al. "Anti-NXP2 antibody-positive dermatomyositis developed after COVID-19 manifesting as type I interferonopathy." Rheumatology 61, no. 4 (November 30, 2021): e90-e92. http://dx.doi.org/10.1093/rheumatology/keab872.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Ruggeri, Paolo, and Gaetano Caramori. "Interferonopathy: a potential link between innate immunity and autoimmunity in the pathogenesis of COPD." American Journal of Physiology-Lung Cellular and Molecular Physiology 317, no. 6 (December 1, 2019): L888—L890. http://dx.doi.org/10.1152/ajplung.00439.2019.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

de Jesus, Adriana A., Anja Brehm, Rachel VanTries, Pascal Pillet, Anne-Sophie Parentelli, Gina A. Montealegre Sanchez, Zuoming Deng, Isabelle Koné Paut, Raphaela Goldbach-Mansky, and Elke Krüger. "Novel proteasome assembly chaperone mutations in PSMG2/PAC2 cause the autoinflammatory interferonopathy CANDLE/PRAAS4." Journal of Allergy and Clinical Immunology 143, no. 5 (May 2019): 1939–43. http://dx.doi.org/10.1016/j.jaci.2018.12.1012.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Okada, Satoshi, Takaki Asano, Kunihiko Moriya, Stephanie Boisson-Dupuis, Masao Kobayashi, Jean-Laurent Casanova, and Anne Puel. "Human STAT1 Gain-of-Function Heterozygous Mutations: Chronic Mucocutaneous Candidiasis and Type I Interferonopathy." Journal of Clinical Immunology 40, no. 8 (August 27, 2020): 1065–81. http://dx.doi.org/10.1007/s10875-020-00847-x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

de Carvalho, Luciana Martins, Gonza Ngoumou, Ji Woo Park, Nadja Ehmke, Nikolaus Deigendesch, Naoki Kitabayashi, Isabelle Melki, et al. "Musculoskeletal Disease in MDA5-Related Type I Interferonopathy: A Mendelian Mimic of Jaccoud's Arthropathy." Arthritis & Rheumatology 69, no. 10 (August 22, 2017): 2081–91. http://dx.doi.org/10.1002/art.40179.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Al-Mayouf, Sulaiman M., Lujayn Akbar, Abdullatif AlEnazi, and Hamoud Al-Mousa. "Autosomal Recessive ISG15 Deficiency Underlies Type I Interferonopathy with Systemic Lupus Erythematosus and Inflammatory Myositis." Journal of Clinical Immunology 41, no. 6 (March 19, 2021): 1361–64. http://dx.doi.org/10.1007/s10875-021-01019-1.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Rood, Julia E., and Edward M. Behrens. "Inherited Autoinflammatory Syndromes." Annual Review of Pathology: Mechanisms of Disease 17, no. 1 (January 24, 2022): 227–49. http://dx.doi.org/10.1146/annurev-pathmechdis-030121-041528.

Full text

Abstract:

Autoinflammation describes a collection of diverse diseases caused by indiscriminate activation of the immune system in an antigen-independent manner. The rapid advancement of genetic diagnostics has allowed for the identification of a wide array of monogenic causes of autoinflammation. While the clinical picture of these syndromes is diverse, it is possible to thematically group many of these diseases under broad categories that provide insight into the mechanisms of disease and therapeutic possibilities. This review covers archetypical examples of inherited autoinflammatory diseases in five major categories: inflammasomopathy, interferonopathy, unfolded protein/cellular stress response, relopathy, and uncategorized. This framework can suggest where future work is needed to identify other genetic causes of autoinflammation, what types of diagnostics need to be developed to care for this patient population, and which options might be considered for novel therapeutic targeting.

APA, Harvard, Vancouver, ISO, and other styles

31

Kasher, Paul R., Emma M. Jenkinson, Valérie Briolat, David Gent, Catherine Morrissey, Leo A. H. Zeef, Gillian I. Rice, Jean-Pierre Levraud, and Yanick J. Crow. "Characterization of samhd1 Morphant Zebrafish Recapitulates Features of the Human Type I Interferonopathy Aicardi-Goutières Syndrome." Journal of Immunology 194, no. 6 (February 11, 2015): 2819–25. http://dx.doi.org/10.4049/jimmunol.1403157.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Kong, Xiao-Fei, Lisa Worley, Darawan Rinchai, Vincent Bondet, Puthen Veettil Jithesh, Marie Goulet, Emilie Nonnotte, et al. "Three Copies of Four Interferon Receptor Genes Underlie a Mild Type I Interferonopathy in Down Syndrome." Journal of Clinical Immunology 40, no. 6 (June 22, 2020): 807–19. http://dx.doi.org/10.1007/s10875-020-00803-9.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Duncan, Christopher J. A., Benjamin J. Thompson, Rui Chen, Gillian I. Rice, Florian Gothe, Dan F. Young, Simon C. Lovell, et al. "Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in STAT2." Science Immunology 4, no. 42 (December 13, 2019): eaav7501. http://dx.doi.org/10.1126/sciimmunol.aav7501.

Full text

Abstract:

Excessive type I interferon (IFNα/β) activity is implicated in a spectrum of human disease, yet its direct role remains to be conclusively proven. We investigated two siblings with severe early-onset autoinflammatory disease and an elevated IFN signature. Whole-exome sequencing revealed a shared homozygous missense Arg148Trp variant in STAT2, a transcription factor that functions exclusively downstream of innate IFNs. Cells bearing STAT2R148W in homozygosity (but not heterozygosity) were hypersensitive to IFNα/β, which manifest as prolonged Janus kinase–signal transducers and activators of transcription (STAT) signaling and transcriptional activation. We show that this gain of IFN activity results from the failure of mutant STAT2R148W to interact with ubiquitin-specific protease 18, a key STAT2-dependent negative regulator of IFNα/β signaling. These observations reveal an essential in vivo function of STAT2 in the regulation of human IFNα/β signaling, providing concrete evidence of the serious pathological consequences of unrestrained IFNα/β activity and supporting efforts to target this pathway therapeutically in IFN-associated disease.

APA, Harvard, Vancouver, ISO, and other styles

34

Buers, Insa, Gillian I. Rice, Yanick J. Crow, and Frank Rutsch. "MDA5-Associated Neuroinflammation and the Singleton–Merten Syndrome: Two Faces of the Same Type I Interferonopathy Spectrum." Journal of Interferon & Cytokine Research 37, no. 5 (May 2017): 214–19. http://dx.doi.org/10.1089/jir.2017.0004.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Meesilpavikkai, Kornvalee, Willem A. Dik, Benjamin Schrijver, Cornelia G. Helden‐Meeuwsen, Marjan A. Versnel, P. Martin Hagen, Emilia K. Bijlsma, Claudia A. L. Ruivenkamp, Margreet J. Oele, and Virgil A. S. H. Dalm. "Efficacy of Baricitinib in the Treatment of Chilblains Associated With Aicardi‐Goutières Syndrome, a Type I Interferonopathy." Arthritis & Rheumatology 71, no. 5 (March 6, 2019): 829–31. http://dx.doi.org/10.1002/art.40805.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Mills, Taylor, Bailee Kain, Erin Lucas, Matt Burchill, Beth Jiron Tamburini, Katherine King, and Eric Pietras. "3097 – AUTOIMMUNE INTERFERONOPATHY INDUCES A ‘TRAINED IMMUNITY’ PROGRAM IN HSC THAT PRIMES MACROPHAGES FOR INCREASED PATHOGEN KILLING AND INFLAMMATORY ACTIVITY." Experimental Hematology 100 (August 2021): S89. http://dx.doi.org/10.1016/j.exphem.2021.12.314.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Cazzato, Salvatore, Alessia Omenetti, Claudia Ravaglia, and Venerino Poletti. "Lung involvement in monogenic interferonopathies." European Respiratory Review 29, no. 158 (December 15, 2020): 200001. http://dx.doi.org/10.1183/16000617.0001-2020.

Full text

Abstract:

Monogenic type I interferonopathies are inherited heterogeneous disorders characterised by early onset of systemic and organ specific inflammation, associated with constitutive activation of type I interferons (IFNs). In the last few years, several clinical reports identified the lung as one of the key target organs of IFN-mediated inflammation. The major pulmonary patterns described comprise children's interstitial lung diseases (including diffuse alveolar haemorrhages) and pulmonary arterial hypertension but diagnosis may be challenging. Respiratory symptoms may be either mild or absent at disease onset and variably associated with systemic or organ specific inflammation. In addition, associated extrapulmonary clinical features may precede lung function impairment by years, and patients may display severe/endstage lung involvement, although this may be clinically hidden during the long-term disease course. Conversely, a few cases of atypical severe lung involvement at onset have been reported without clinically manifested extrapulmonary signs. Hence, a multidisciplinary approach involving pulmonologists, paediatricians and rheumatologists should always be considered when a monogenic interferonopathy is suspected. Pulmonologists should also be aware of the main pattern of presentation to allow prompt diagnosis and a targeted therapeutic strategy. In this regard, promising therapeutic strategies rely on Janus kinase-1/2 (JAK-1/2) inhibitors blocking the type I IFN-mediated intracellular cascade.

APA, Harvard, Vancouver, ISO, and other styles

38

Kataoka, Shinsuke, Nozomu Kawashima, Yusuke Okuno, Hideki Muramatsu, Shunsuke Miwata, Kotaro Narita, Motoharu Hamada, et al. "Successful treatment of a novel type I interferonopathy due to a de novo PSMB9 gene mutation with a Janus kinase inhibitor." Journal of Allergy and Clinical Immunology 148, no. 2 (August 2021): 639–44. http://dx.doi.org/10.1016/j.jaci.2021.03.010.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Poeschla, Eric M., and Laura Bankers. "Development of interferon-stimulated gene expression from embryogenesis through adulthood, with and without constitutive MDA5 pathway activation." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 68.15. http://dx.doi.org/10.4049/jimmunol.204.supp.68.15.

Full text

Abstract:

Abstract Pathogen-associated molecular patterns, e.g. dsRNA, activate expression of interferon-stimulated genes (ISGs), which protects hosts from infection. While transient ISG upregulation is essential for effective innate immunity, constitutive activation typically causes harmful autoimmunity in mice and humans, often including severe developmental abnormalities. We have shown that transgenic mice expressing a picornavirus RNA-dependent RNA polymerase outside the viral context (RdRP mice) exhibit lifelong, MDA5-dependent, and quantitatively dramatic upregulation of many ISGs, which confers broad viral infection resistance. Remarkably, RdRP mice never develop autoinflammation, interferonopathy, or any other discernible abnormalities. Here we used RNA-seq and other methods to analyze ISG expression across five time points from fetal development to adulthood in both wild-type and RdRP mice. In RdRP mice, the proportion of upregulated ISGs increased during development, with the most dramatic induction occurring two weeks postnatally. The immensely amplified ISG profile is then maintained lifelong. We further determined that blocking the type I interferon receptor reverses the amplified ISG transcriptome in adults. Molecular pathways and biological functions associated with innate immune signaling are only activated postnatally, suggesting dampened fetal responsiveness to innate immune stimuli. Similarly, functions supporting viral replication are only inhibited postnatally. In conclusion, the uniquely tolerated amplified ISG state of RdRP mice is mostly triggered early postnatally, is maintained through adulthood, and requires ongoing type I IFN signaling to maintain the augmented innate immune state.

APA, Harvard, Vancouver, ISO, and other styles

40

Bryant, Andrew J., Ann Pham, Himanshu Gogoi, Carly R. Mitchell, Faye Pais, and Lei Jin. "The Third Man: DNA sensing as espionage in pulmonary vascular health and disease." Pulmonary Circulation 11, no. 1 (January 2021): 204589402199657. http://dx.doi.org/10.1177/2045894021996574.

Full text

Abstract:

For as long as nucleic acids have been utilized to vertically and horizontally transfer genetic material, living organisms have had to develop methods of recognizing cytosolic DNA as either pathogenic (microbial invasion) or physiologic (mitosis and cellular proliferation). Derangement in key signaling molecules involved in these pathways of DNA sensing result in a family of diseases labeled interferonopathies. An interferonopathy, characterized by constitutive expression of type I interferons, ultimately manifests as severe autoimmune disease at a young age. Afflicted patients present with a constellation of immune-mediated conditions, including primary lung manifestations such as pulmonary fibrosis and pulmonary hypertension. The latter condition is especially interesting in light of the known role that DNA damage plays in a variety of types of inherited and induced pulmonary hypertension, with free DNA detection elevated in the circulation of affected individuals. While little is known regarding the role of cytosolic DNA sensing in development of pulmonary vascular disease, exciting new research in the related fields of immunology and oncology potentially sheds light on future areas of fruitful exploration. As such, the goal of this review is to summarize the state of the field of nucleic acid sensing, extrapolating common shared pathways that parallel our knowledge of pulmonary hypertension, in a molecular and cell-specific manner. Principles of DNA sensing related to known pulmonary injury inducing stimuli are also evaluated, in addition to potential therapeutic targets. Finally, future directions in pulmonary hypertension research and treatments will be briefly discussed.

APA, Harvard, Vancouver, ISO, and other styles

41

Adang, Laura, Francesco Gavazzi, Micaela De Simone, Elisa Fazzi, Jessica Galli, Jamie Koh, Julia Kramer-Golinkoff, et al. "Developmental Outcomes of Aicardi Goutières Syndrome." Journal of Child Neurology 35, no. 1 (September 27, 2019): 7–16. http://dx.doi.org/10.1177/0883073819870944.

Full text

Abstract:

Aicardi Goutières syndrome is a monogenic interferonopathy caused by abnormalities in the intracellular nucleic acid sensing machinery ( TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or IFIH1). Most individuals affected by Aicardi Goutières syndrome exhibit some degree of neurologic impairment, from spastic paraparesis with relatively preserved cognition to tetraparesis and severe intellectual disability. Because of this heterogeneity, it is important to fully characterize the developmental trajectory in Aicardi Goutières syndrome. To characterize the clinical presentation in Aicardi Goutières syndrome, early features were collected from an international cohort of children (n = 100) with genetically confirmed Aicardi Goutières syndrome. There was a heterogeneous age of onset, with overlapping clusters of presenting symptoms: altered mental status, systemic inflammatory symptoms, and acute neurologic disability. Next, we created genotype-specific developmental milestone acquisition curves. Individuals with microcephaly or TREX1-related Aicardi Goutières syndrome secondary were the most severely affected and less likely to reach milestones, including head control, sitting, and nonspecific mama/dada. Individuals affected by SAMHD1, IFIH1, and ADAR attained the most advanced milestones, with 44% achieving verbal communication and 31% independently ambulating. Retrospective function scales (Gross Motor Function Classification System, Manual Ability Classification System, and Communication Function Classification System) demonstrated that two-thirds of the Aicardi Goutières syndrome population are severely affected. Our results suggest multifactorial influences on developmental trajectory, including a strong contribution from genotype. Further studies are needed to identify the additional factors that influence overall outcomes to better counsel families and to design clinical trials with appropriate clinical endpoints.

APA, Harvard, Vancouver, ISO, and other styles

42

Sandling, Johanna K., Pascal Pucholt, Lina Hultin Rosenberg, Fabiana H. G. Farias, Sergey V. Kozyrev, Maija-Leena Eloranta, Andrei Alexsson, et al. "Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing." Annals of the Rheumatic Diseases 80, no. 1 (October 9, 2020): 109–17. http://dx.doi.org/10.1136/annrheumdis-2020-218636.

Full text

Abstract:

ObjectivesSystemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE.MethodsWe undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS).ResultsWe identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes.ConclusionsOur results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.

APA, Harvard, Vancouver, ISO, and other styles

43

Tesser, Alessandra, Giulia Maria Piperno, Alessia Pin, Elisa Piscianz, Valentina Boz, Federica Benvenuti, and Alberto Tommasini. "Priming of the cGAS-STING-TBK1 Pathway Enhances LPS-Induced Release of Type I Interferons." Cells 10, no. 4 (April 1, 2021): 785. http://dx.doi.org/10.3390/cells10040785.

Full text

Abstract:

Cytoplasmic nucleic acids sensing through cGAS-STING-TBK1 pathway is crucial for the production of antiviral interferons (IFNs). IFN production can also be induced by lipopolysaccharide (LPS) stimulation through Toll-like receptor 4 (TLR4) in appropriate conditions. Of note, both IFN production and dysregulated LPS-response could play a role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Indeed, LPS can trigger SLE in lupus-prone mice and bacterial infections can induce disease flares in human SLE. However, the interactions between cGAS and TLR4 pathways to IFNs have been poorly investigated. To address this issue, we studied LPS-stimulation in cellular models with a primed cGAS-STING-TBK1 pathway. cGAS-stimulation was naturally sustained by undigested self-nucleic acids in fibroblasts from DNase2-deficiency interferonopathy, whilst it was pharmacologically obtained by cGAMP-stimulation in THP1 cells and murine bone marrow-derived dendritic cells. We showed that cells with a primed cGAS-STING-TBK1 pathway displayed enhanced IFNs production after TLR4-challenge. STING-inhibition did not affect IFN production after LPS alone, but prevented the amplified IFN production in cGAMP-primed cells, suggesting that functional STING is required for priming-dependent enhancement. Furthermore, we speculated that an increased PIK3AP1 expression in DNase2-deficient fibroblasts may link cGAMP-priming with increased LPS-induced IFN production. We showed that both the hyper-expression of PIK3API and the enhanced LPS-induced IFN production can be contrasted by STING inhibitors. Our results may explain how bacterial LPS can synergize with cGAS-pathway in promoting the development of SLE-like autoimmunity.

APA, Harvard, Vancouver, ISO, and other styles

44

Daou, Salima, Manisha Talukdar, Jinle Tang, Beihua Dong, Shuvojit Banerjee, Yize Li, Nicole M. Duffy, et al. "A phenolic small molecule inhibitor of RNase L prevents cell death from ADAR1 deficiency." Proceedings of the National Academy of Sciences 117, no. 40 (September 21, 2020): 24802–12. http://dx.doi.org/10.1073/pnas.2006883117.

Full text

Abstract:

The oligoadenylate synthetase (OAS)–RNase L system is an IFN-inducible antiviral pathway activated by viral infection. Viral double-stranded (ds) RNA activates OAS isoforms that synthesize the second messenger 2-5A, which binds and activates the pseudokinase-endoribonuclease RNase L. In cells, OAS activation is tamped down by ADAR1, an adenosine deaminase that destabilizes dsRNA. Mutation of ADAR1 is one cause of Aicardi-Goutières syndrome (AGS), an interferonopathy in children. ADAR1 deficiency in human cells can lead to RNase L activation and subsequent cell death. To evaluate RNase L as a possible therapeutic target for AGS, we sought to identify small-molecule inhibitors of RNase L. A 500-compound library of protein kinase inhibitors was screened for modulators of RNase L activity in vitro. We identified ellagic acid (EA) as a hit with 10-fold higher selectivity against RNase L compared with its nearest paralog, IRE1. SAR analysis identified valoneic acid dilactone (VAL) as a superior inhibitor of RNase L, with 100-fold selectivity over IRE1. Mechanism-of-action analysis indicated that EA and VAL do not bind to the pseudokinase domain of RNase L despite acting as ATP competitive inhibitors of the protein kinase CK2. VAL is nontoxic and functional in cells, although with a 1,000-fold decrease in potency, as measured by RNA cleavage activity in response to treatment with dsRNA activator or by rescue of cell lethality resulting from self dsRNA induced by ADAR1 deficiency. These studies lay the foundation for understanding novel modes of regulating RNase L function using small-molecule inhibitors and avenues of therapeutic potential.

APA, Harvard, Vancouver, ISO, and other styles

45

Wang, Qingde, Xinfeng Guo, Yi Sheng, Tony Wang, Richard Steinman, and Timothy R. Billiar. "An AGS associated mutation causes cellular RNA editing deficiency in mouse brain which lead to IFN pathway activation, mimicking the interferonopathy of patient brains." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 15.07. http://dx.doi.org/10.4049/jimmunol.206.supp.15.07.

Full text

Abstract:

Abstract Objective: To determine whether and how a gene mutation found in Aicardi-Goutières syndrome (AGS), a severe autoimmune encephalopathy, is sufficient to activate the interferon signaling pathway in the brain. Background: Genetic mutations in six coding genes were found associated with AGS patients, however, none of them was demonstrated able to cause IFN pathway activation in the brain tissue, the most critical pathogenetic change of AGS. How an AGS-associated mutation activates the IFN pathway in the brain that leads to brain injury remains to be revealed. Methods: A knock-In mouse model was established through CRISPR/Cas9 gene editing approach, in which a single G>T nucleotide replacement was introduced into mouse genome, that encodes the change for p.K948N in mouse ADAR1 at its catalytic domain, equivalent to the p.K999N mutation found in AGS patients. We analyzed the enzyme activity of ADAR1 on the neuron specific mRNA substrates in the KI mice through RNA sequencing, the activities of IFN signaling pathway by measuring expressions of IFN stimulated inflammatory cytokines. Brain injury was observed by pathology studies. Results: The genetic mutation was confirmed. RNA transcription and protein translation were tested not affected by the mutation. The cellular RNA process in neurons was altered due to decreased enzyme activity of mutant ADAR1 on certain mRNA substrates. ISG expression were significantly increased at RNA and protein levels. Cell death in the brain was observed in the KI mice. Conclusion: A mouse model was successfully established recapitulating the genetic and innate immunologic features of AGS. An ADAR1 gene mutation is sufficient to cause IFN pathway activation in the brain through altering cellular RNA process.

APA, Harvard, Vancouver, ISO, and other styles

46

Su, Yu-Jih, Hung-Yu Lin, Shao-Wen Weng, Cheng-Hsien Lu, Ching-Yi Lin, Wen-Chan Chiu, and Pei-Wen Wang. "Metformin Represses Interferonopathy Through Suppression of Melanoma Differentiation-Associated Protein 5 and Mitochondrial Antiviral Signaling Protein Activation: Comment on the Article by Wang et al." Arthritis & Rheumatology 68, no. 12 (November 28, 2016): 3042–43. http://dx.doi.org/10.1002/art.39935.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

David, Clémence, and Marie-Louise Frémond. "Lung Inflammation in STING-Associated Vasculopathy with Onset in Infancy (SAVI)." Cells 11, no. 3 (January 18, 2022): 318. http://dx.doi.org/10.3390/cells11030318.

Full text

Abstract:

STING-associated vasculopathy with onset in infancy (SAVI) is a type I interferonopathy caused by gain-of-function mutations in STING1 encoding stimulator of interferon genes (STING) protein. SAVI is characterized by severe inflammatory lung disease, a feature not observed in previously described type I interferonopathies i.e., Mendelian autoinflammatory disorders defined by constitutive activation of the type I interferon (IFN) pathway. Molecular defects in nucleic acid metabolism or sensing are central to the pathophysiology of these diseases, with such defects occurring at any step of the tightly regulated pathway of type I IFN production and signaling (e.g., exonuclease loss of function, RNA-DNA hybrid accumulation, constitutive activation of adaptor proteins such as STING). Among over 30 genotypes, SAVI and COPA syndrome, whose pathophysiology was recently linked to a constitutive activation of STING signaling, are the only type I interferonopathies presenting with predominant lung involvement. Lung disease is the leading cause of morbidity and mortality in these two disorders which do not respond to conventional immunosuppressive therapies and only partially to JAK1/2 inhibitors. In human silicosis, STING-dependent sensing of self-DNA following cell death triggered by silica exposure has been found to drive lung inflammation in mice and human models. These recent findings support a key role for STING and nucleic acid sensing in the homeostasis of intrinsic pulmonary inflammation. However, mechanisms by which monogenic defects in the STING pathway lead to pulmonary damages are not yet fully elucidated, and an improved understanding of such mechanisms is fundamental to improved future patient management. Here, we review the recent insights into the pathophysiology of SAVI and outline our current understanding of self-nucleic acid-mediated lung inflammation in humans.

APA, Harvard, Vancouver, ISO, and other styles

48

Yoshikawa, T., K. Azuma, T. Furukawa, M. Tamura, T. Hashimoto, M. Morimoto, N. Azuma, and K. Matsui. "AB0311 INCREASED LEVELS OF SERUM WISTERIA FLORIBUNDA AGGLUTININPOSITIVE MAC-2 BINDING PROTEIN IN RHEUMATIC DISEASES INCLUDING SLE." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1181.1–1181. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1494.

Full text

Abstract:

Background:Mac-2 binding protein is a cell-adhesive glycoprotein of the extracellular matrix secreted as a ligand of galectin-3 (Mac-2). Recently, a Wisteria floribunda agglutinin positive-M2BP (M2BP) assay developed using a lectin-antibody sandwich immunoassay has shown promise as a new fibrotic marker in liver fibrosis and interstitial lung disease (ILD) to detect unique fibrosis-related glycoalteration.Objectives:The aim of this study is to evaluate the utility of serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels in patients with rheumatic diseases (RD).Methods:We retrospectively measured serum M2BPGi levels in 68 patients with RD and 16 healthy controls (HC). There were no patients of cirrhosis and active hepatitis. Serum levels of M2BPGi were measured using HISCL M2BP glycosylation isomer Assay Kit. We examined the relationship between serum M2BPGi levels and clinical parameters in patients with RD.Results:In patients with RD, the median age was 62.0 years and 79.4% of them were female.Serum M2BPGi levels were significantly higher in patients with RD than in HC (median 0.98 cutoff index [COI], 0.32 COI, respectively; P < 0.00001). Patients with SLE tended to have higher serum M2BPGi levels than other rheumatic diseases.In patients with RD, a significant correlation was not found between serum M2BP levels and inflammation markers such as CRP or ferritin. However, serum M2BPGi levels were significantly correlated with B cell activation markers such as immunoglobulin free light chain and IgG (r = 0.588, 0.504) and T cell activation marker such as sIL-2R (r = 0.408).Conclusion:Most of the rheumatic diseases in this study were considered to be type I interferonopathy diseases such as rheumatoid arthritis, Sjogren’s syndrome, inflammatory myositis, scleroderma and SLE.Serum M2BPGi was reported to have a significant correlation with SLE disease activity [SS Ahn et al. Lupus. 2018; 27: 771], and also to have a significant correlation with Gakectin-9, a novel biomarker for IFN signiture [Lucas L van den Hoogen et al. Ann Rheum Dis. 2018; 77: 1810].So, it was suggested that serum M2BPGi may be a novel biomarker that indirectly indicates how much IFN is activated in rheumatic diseases.Disclosure of Interests:None declared

APA, Harvard, Vancouver, ISO, and other styles

49

Stathopoulou, C., D. Konstantopoulos, S. Papanikolaou, G. Vatsellas, G. Panagopoulos, P. Sidiropoulos, and G. Bertsias. "POS0404 IFNα-MEDIATED METABOLIC REPROGRAMMING IN HUMAN SLE MONOCYTES INVOLVES PERTURBATIONS IN GLYCOLYTIC AND LIPID METABOLISM TO REGULATE PROINFLAMMATORY MARKERS AND CYTOKINES." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 458.1–458. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2035.

Full text

Abstract:

BackgroundSystemic Lupus Erythematosus (SLE) is a prototype interferonopathy characterized by multiple organ damage1. Metabolomic analyses of patient-derived sera indicate distinct metabolic pertubations in oxidative and lipid metabolism2,3. Among innate effectors, monocytes (Mo) are implicated in SLE pathogenesis and also display a perturbed metabolic phenotype4.ObjectivesBased on previous data indicating a prominent IFNα-gene signature in SLE monocytes even during disease remission5, we herein sought to delineate the metabolic repercussion of IFNα signaling contributing to SLE autoimmunity.MethodsUsing transcriptomic data, we compared the enriched metabolic categories of IFNα(+) and IFNα(-) SLE-Mo6. In order to compare metabolic perturbations pertaining to SLE, we performed transcriptomic Gene Set Enrichment Analysis (GSEA)7 from in vitro cultured IFNα-activated Mo. We supplemented the analysis with selective ex vivo biochemical inhibition of the metabolic pathways arising from the GSEA and evaluated the effect on inflammatory markers of healthy IFNα-Mo.ResultsWe found a statistically significant enrichment of transcripts associated with glycolytic metabolism and lipid biosynthetic and catabolic processes in both IFNα(+)-SLE Mo and healthy IFNα-Mo, but not in IFNα(-)-SLE Mo, which in turn resembled healthy-Mo. Additionally, transcripts associated with cholesterol biosynthetic processes such PMVK, SQLE, LSS, DHCR7, and LDLR, MVK, FFT1 were significantly upregulated in IFNα(+)-SLE Mo and healthy IFNα-Mo respectively. In accordance, blockade of either glycolysis with the use of 2-DG hexokinase inhibitor, or mevalonic acid synthesis with the use of fluvastatin, attenuated proinflammatory cytokine secretion (IL6, CXCL10) associated with IFN-response in both IFNα(+)-SLE Mo and healthy IFNα-Mo.ConclusionOur results link IFNα mediated metabolic shifts in Mo with corresponding metabolic perturbations found in SLE patient-Mo. Pending further confirmation with targeted metabolomics, these data further rationalize the use of IFN blockade and also suggest the potential use of specific metabolites as novel therapeutic targets in SLE.References[1]Crampton, S. P., Morawski, P. A. & Bolland, S. Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus. Dis. Model. Mech. 9, 1033–1046 (2014).[2]Yan, B. et al. Serum metabolomic profiling in patients with systemic lupus erythematosus by GC/MS. Mod. Rheumatol. 26, 914–922 (2016).[3]Gkirtzimanaki, K. et al. IFNα impairs autophagic degradation of mtDNA promoting autoreactivity of SLE monocytes in a STING-dependent fashion. Cell Rep. 25, 921-933.e5 (2018).[4]Huang, N. & Perl, A. Metabolism as a target for modulation in autoimmune diseases. Trends Immunol. 39, 562–576 (2018).[5]Panousis, N. I. et al. Combined genetic and transcriptome analysis of patients with SLE : distinct, targetable signatures for susceptibility and severity. Ann. Rheum. Dis. 78, 1079–1089 (2019).[6]El-Sherbiny, Y. M. et al. A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features. Sci. Rep. 8, 5793 (2018).[7]Subramanian, A. et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. 102, 15545–15550 (2005).Disclosure of InterestsNone declared.

APA, Harvard, Vancouver, ISO, and other styles

50

Pennisi, Alessandra, Agnès Rötig, Charles-Joris Roux, Raphaël Lévy, Marco Henneke, Jutta Gärtner, Pelin Teke Kisa, et al. "Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?" Journal of Medical Genetics, November 16, 2020, jmedgenet—2020–107367. http://dx.doi.org/10.1136/jmedgenet-2020-107367.

Full text

Abstract:

BackgroundBiallelic variants in PNPT1 cause a mitochondrial disease of variable severity. PNPT1 (polynucleotide phosphorylase) is a mitochondrial protein involved in RNA processing where it has a dual role in the import of small RNAs into mitochondria and in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This, in turn, prevents the activation of type I interferon response. Detailed neuroimaging findings in PNPT1-related disease are lacking with only a few patients reported with basal ganglia lesions (Leigh syndrome) or non-specific signs.Objective and methodsTo document neuroimaging data in six patients with PNPT1 highlighting novel findings.ResultsTwo patients exhibited striatal lesions compatible with Leigh syndrome; one patient exhibited leukoencephalopathy and one patient had a normal brain MRI. Interestingly, two unrelated patients exhibited cystic leukoencephalopathy resembling RNASET2-deficient patients, patients with Aicardi-Goutières syndrome (AGS) or congenital CMV infection.ConclusionWe suggest that similar to RNASET2, PNPT1 be searched for in the setting of cystic leukoencephalopathy. These findings are in line with activation of type I interferon response observed in AGS, PNPT1 and RNASET2 deficiencies, suggesting a common pathophysiological pathway and linking mitochondrial diseases, interferonopathies and immune dysregulations.

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!