Journal articles on the topic 'Autoimmune diseases Australia'
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Daniel, Benjamin S., Andrew Dermawan, and Dédée F. Murrell. "The Autoimmune Blistering Diseases in Australia: Status and Services." Dermatologic Clinics 29, no. 4 (October 2011): 687–90. http://dx.doi.org/10.1016/j.det.2011.07.002.
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Batzloff, Michael R., David McMillan, and Manisha Pandey. "Progress towards a vaccine for Streptococcus pyogenes." Microbiology Australia 30, no. 5 (2009): 187. http://dx.doi.org/10.1071/ma09187.
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Infection with Streptococcus pyogenes (group A streptococcus, GAS) can lead to rheumatic fever (RF) and rheumatic heart disease (RHD), which are significant health concerns in the Indigenous populations of developed countries, including Australian Aboriginal people. The global burden of GAS diseases had been recently reviewed 1 and multiple studies have demonstrated the high burden of these diseases in Australia. RF and RHD are autoimmune type diseases, in which T-cells and antibodies targeting the bacteria may also cross-react with human tissues, therefore rendering a whole cell vaccine impractical.
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Wong, Peter K. K., Hanish Bagga, Claire Barrett, Paddy Hanrahan, Doug Johnson, Amel Katrib, Karin Leder, et al. "A practical approach to vaccination of patients with autoimmune inflammatory rheumatic diseases in Australia." Internal Medicine Journal 47, no. 5 (May 2017): 491–500. http://dx.doi.org/10.1111/imj.13371.
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Adams, Christi L., and John N. A. Hooper. "A revision of Australian Erylus (Porifera : Demospongiae : Astrophorida : Geodiidae) with a tabular review of worldwide species." Invertebrate Systematics 15, no. 3 (2001): 319. http://dx.doi.org/10.1071/it00028.
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ErylusGray (Porifera: Geodiidae) has been recorded in Australian waters from two antiquated reports (E. lendenfeldi Sollas, 1888 and E. proximus Dendy, 1916). These two species are redescribed. From more recent collections from the Great Barrier Reef, Coral Sea, southern Queensland and Western Australia four new species (E. amissus, E. circus, E. citrus and E. fromonta, spp. nov.) were discovered and are described. One other, presently unrecognisable, species from an antiquated museum slide preparation is also described. A tabular review of species worldwide is also provided. Erylus has been an important source of novel bioactive compounds, including those with antitumor and antifungal properties and that are helpful in combating autoimmune diseases (including HIV). This discovery of four new species, increasing the diversity of the genus by 66% in Australian waters, has important implications pertaining to the existence of new compounds, or analogues of existing compounds unique to Erylus, as potential therapeutic marine natural products.
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Dow, Coad Thomas, and Laith Kidess. "BCG Vaccine—The Road Not Taken." Microorganisms 10, no. 10 (September 27, 2022): 1919. http://dx.doi.org/10.3390/microorganisms10101919.
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The Bacillus Calmette-Guérin (BCG) vaccine has been used for over one hundred years to protect against the most lethal infectious agent in human history, tuberculosis. Over four billion BCG doses have been given and, worldwide, most newborns receive BCG. A few countries, including the United States, did not adopt the WHO recommendation for routine use of BCG. Moreover, within the past several decades, most of Western Europe and Australia, having originally employed routine BCG, have discontinued its use. This review article articulates the impacts of those decisions. The suggested consequences include increased tuberculosis, increased infections caused by non-tuberculous mycobacteria (NTM), increased autoimmune disease (autoimmune diabetes and multiple sclerosis) and increased neurodegenerative disease (Parkinson’s disease and Alzheimer’s disease). This review also offers an emerged zoonotic pathogen, Mycobacteriumavium ss. paratuberculosis (MAP), as a mostly unrecognized NTM that may have a causal role in some, if not all, of these diseases. Current clinical trials with BCG for varied infectious, autoimmune and neurodegenerative diseases have brought this century-old vaccine to the fore due to its presumed immuno-modulating capacity. With its historic success and strong safety profile, the new and novel applications for BCG may lead to its universal use–putting the Western World back onto the road not taken.
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Foo, Damien, Mohinder Sarna, Gavin Pereira, Hannah C. Moore, and Annette K. Regan. "Prenatal influenza vaccination and allergic and autoimmune diseases in childhood: A longitudinal, population-based linked cohort study." PLOS Medicine 19, no. 4 (April 5, 2022): e1003963. http://dx.doi.org/10.1371/journal.pmed.1003963.
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Background Few studies have evaluated the effect of maternal influenza vaccination on the development of allergic and autoimmune diseases in children beyond 6 months of age. We aimed to investigate the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and subsequent diagnosis of allergic and autoimmune diseases. Methods and findings This longitudinal, population-based linked cohort study included 124,760 singleton, live-born children from 106,206 mothers in Western Australia (WA) born between April 2012 and July 2016, with up to 5 years of follow-up from birth. In our study cohort, 64,169 (51.4%) were male, 6,566 (5.3%) were Aboriginal and/or Torres Strait Islander children, and the mean age at the end of follow-up was 3.0 (standard deviation, 1.3) years. The exposure was receipt of seasonal IIV during pregnancy. The outcomes were diagnosis of an allergic or autoimmune disease, including asthma and anaphylaxis, identified from hospital and/or emergency department (ED) records. Inverse probability of treatment weights (IPTWs) accounted for baseline probability of vaccination by maternal age, Aboriginal and/or Torres Strait Islander status, socioeconomic status, body mass index, parity, medical conditions, pregnancy complications, prenatal smoking, and prenatal care. The models additionally adjusted for the Aboriginal and/or Torres Strait Islander status of the child. There were 14,396 (11.5%) maternally vaccinated children; 913 (6.3%) maternally vaccinated and 7,655 (6.9%) maternally unvaccinated children had a diagnosis of allergic or autoimmune disease, respectively. Overall, maternal influenza vaccination was not associated with diagnosis of an allergic or autoimmune disease (adjusted hazard ratio [aHR], 1.02; 95% confidence interval [CI], 0.95 to 1.09). In trimester-specific analyses, we identified a negative association between third trimester influenza vaccination and the diagnosis of asthma (n = 40; aHR, 0.70; 95% CI, 0.50 to 0.97) and anaphylaxis (n = 36; aHR, 0.67; 95% CI, 0.47 to 0.95).We did not capture outcomes diagnosed in a primary care setting; therefore, our findings are only generalizable to more severe events requiring hospitalization or presentation to the ED. Due to small cell sizes (i.e., <5), estimates could not be determined for all outcomes after stratification. Conclusions In this study, we observed no association between in utero exposure to influenza vaccine and diagnosis of allergic or autoimmune diseases. Although we identified a negative association of asthma and anaphylaxis diagnosis when seasonal IIV was administered later in pregnancy, additional studies are needed to confirm this. Overall, our findings support the safety of seasonal inactivated influenza vaccine during pregnancy in relation to allergic and autoimmune diseases in early childhood and support the continuation of current global maternal vaccine programs and policies.
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Barth, Dylan D., Marianne J. Mullane, Claudia Sampson, Coco Chou, Janessa Pickering, Mark P. Nicol, Mark R. Davies, Jonathan Carapetis, and Asha C. Bowen. "Missing Piece Study protocol: prospective surveillance to determine the epidemiology of group A streptococcal pharyngitis and impetigo in remote Western Australia." BMJ Open 12, no. 4 (April 2022): e057296. http://dx.doi.org/10.1136/bmjopen-2021-057296.
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IntroductionGroup A β-haemolytic Streptococcus (GAS), a Gram-positive bacterium, causes skin, mucosal and systemic infections. Repeated GAS infections can lead to autoimmune diseases acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Aboriginal and Torres Strait Islander peoples in Australia have the highest rates of ARF and RHD in the world. Despite this, the contemporaneous prevalence and incidence of GAS pharyngitis and impetigo in remote Australia remains unknown. To address this, we have designed a prospective surveillance study of GAS pharyngitis and impetigo to collect coincident contemporary evidence to inform and enhance primary prevention strategies for ARF.Methods and analysisThe Missing Piece Study aims to document the epidemiology of GAS pharyngitis and impetigo through collection of clinical, serological, microbiological and bacterial genomic data among remote-living Australian children. The study comprises two components: (1) screening of all children at school for GAS pharyngitis and impetigo up to three times a year and (2) weekly active surveillance visits to detect new cases of pharyngitis and impetigo. Environmental swabbing in remote schools will be included, to inform environmental health interventions. In addition, the application of new diagnostic technologies, microbiome analysis and bacterial genomic evaluations will enhance primary prevention strategies, having direct bearing on clinical care, vaccine development and surveillance for vaccine clinical trials.Ethics and disseminationEthical approval has been obtained from the Western Australian Aboriginal Health Ethics Committee (Ref: 892) and Human Research Ethics Committee of the University of Western Australia (Ref: RA/4/20/5101). Study findings will be shared with community members, teachers and children at participating schools, together with academic and medical services. Sharing findings in an appropriate manner is important and will be done in a suitable way which includes plain language summaries and presentations. Finally, findings and updates will also be disseminated to collaborators, researchers and health planners through peer-reviewed journal publications.
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Ekundayo, Temitope C., and Anthony I. Okoh. "Systematic Assessment of Mycobacterium avium Subspecies Paratuberculosis Infections from 1911–2019: A Growth Analysis of Association with Human Autoimmune Diseases." Microorganisms 8, no. 8 (August 10, 2020): 1212. http://dx.doi.org/10.3390/microorganisms8081212.
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Mycobacterium avium subsp. paratuberculosis (MAP) is an understudied pathogen worldwide with continuous implications in human autoimmune diseases (ADs). The awareness of MAP appears to be low in many places and its research is at infant stage in many countries. The lack of worldwide coverage of the MAP research landscape calls for urgent research attention and prioritization. This present study aimed to assess MAP global research productivity with an emphasis on its implications in ADs via bibliometric and growth analytic frameworks from authors, countries, institutions, international, disciplines and collaboration network perspectives. MAP primary articles were retrieved from the Scopus database and the Web of Science from 1911 to 2019 via title-specific algorithm. Analytic results of dataset yielded a total of 3889 articles from 581 journals and 20.65 average citations per documents. The annual growth rate of MAP research for the period was 6.31%. Based on a country’s productivity (articles (%), freq. of publication (%)), the USA (887 (22.81%), 26.72%), and Australia (236 (6.07%), 6.07%) ranked the top 2 countries but Egypt and Germany had the highest average growth rate (AGR, 170%) in the last 3 years. MAP studies are generally limited to Europe, Australia, Asia, South America and few nations in Africa. It had positive growth rate (30%–100%) in relation to type 1 diabetes mellitus and rheumatoid arthritis ADs; food science and technology, immunology, agriculture, pathology, and research and experimental medicine, wildlife, environments, virulence, disease resistance, meat and meat products, osteopontin, waste milk and slurry/sludge digestion subjects; but negative growth (−130% to −30%) in ulcerative colitis and Parkinson’s disease and no growth in multiple sclerosis, sarcoidosis, thyroid disorders, psoriasis, and lupus. The mapping revealed a gross lack of collaboration networking in terms of authorship, (intra- and inter-) nationally and institutionally with a generalized collaboration index of 1.82. In conclusion, inadequate resources-, knowledge- and scientific-networking hampered growth and awareness of MAP research globally. The study recommends further research to strengthen evidence of MAP’s epidemiologic prevalence in ADs and proffer practical solution(s) for drug development and point-of-care diagnostics amongst other extended themes.
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Borradale, David, and Michael Kimlin. "Vitamin D in health and disease: an insight into traditional functions and new roles for the ‘sunshine vitamin’." Nutrition Research Reviews 22, no. 2 (November 10, 2009): 118–36. http://dx.doi.org/10.1017/s0954422409990102.
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Vitamin D is unique among the vitamins in that man can synthesise it via the action of UV radiation upon the skin. This combined with its ability to act on specific target tissues via vitamin D receptors (VDR) make its classification as a steroid hormone more appropriate. While vitamin D deficiency is a recognised problem in some northern latitude countries, recent studies have shown that even in sunny countries, such as Australia, vitamin D deficiency may be more prevalent than first thought. Vitamin D is most well known for its role in bone health; however, the discovery of VDR on a wide variety of tissue types has also opened up roles for vitamin D far beyond traditional bone health. These include possible associations with autoimmune diseases such as multiple sclerosis and inflammatory bowel diseases, cancer, CVD and muscle strength. First, this paper presents an overview of the two sources of vitamin D: exposure to UVB radiation and food sources of vitamin D, with particular focus on both Australian and international studies on dietary vitamin D intake and national fortification strategies. Second, the paper reviews recent epidemiological and experimental evidence linking vitamin D and its role in health and disease for the major conditions linked to suboptimal vitamin D, while identifying significant gaps in the research and possible future directions for research.
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RAMOS-CASALS, MANUEL, SANDRA MUÑOZ, FRANCISCO MEDINA, LUIS-JAVIER JARA, JOSÉ ROSAS, JAIME CALVO-ALEN, PILAR BRITO-ZERÓN, XAVIER FORNS, and JOSE-MARIA SÁNCHEZ-TAPIAS. "Systemic Autoimmune Diseases in Patients with Hepatitis C Virus Infection: Characterization of 1020 Cases (The HISPAMEC Registry)." Journal of Rheumatology 36, no. 7 (April 15, 2009): 1442–48. http://dx.doi.org/10.3899/jrheum.080874.
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Objective.To describe the clinical and immunologic characteristics of a large series of patients with systemic autoimmune diseases (SAD) associated with chronic hepatitis C virus (HCV) infection.Methods.The HISPAMEC Registry is a multicenter international study group dedicated to collecting data on patients diagnosed with SAD with serological evidence of chronic HCV infection. The information sources are cases reported by physicians of the HISPAMEC Study Group and periodic surveillance of reported cases by a Medline search updated up to December 31, 2007.Results.One thousand twenty HCV patients with SAD were included in the registry. Patients were reported from Southern Europe (60%), North America (15%), Asia (14%), Northern Europe (9%), South America (1%), and Australia (1%). Countries reporting the most cases were Spain (236 cases), France (222 cases), Italy (144 cases), USA (120 cases), and Japan (95 cases). The most frequently reported SAD were Sjögren’s syndrome (SS; 483 cases), rheumatoid arthritis (RA; 150 cases), systemic lupus erythematosus (SLE; 129 cases), polyarteritis nodosa (78 cases), antiphospholipid syndrome (59 cases), inflammatory myopathies (39 cases), and sarcoidosis (28 cases). Twenty patients had 2 or more SAD. Epidemiological data were available in 677 cases. Four hundred eighty-seven (72%) patients were female and 186 (28%) male, with a mean age of 49.5 ± 1.0 years at SAD diagnosis and 50.5 ± 1.1 years at diagnosis of HCV infection. The main immunologic features were antinuclear antibody (ANA) in 61% of patients, rheumatoid factor (RF) in 57%, hypocomplementemia in 52%, and cryoglobulins in 52%. The main differential aspect between primary and HCV-related SAD was the predominance of cryoglobulinemic-related markers (cryoglobulins, RF, hypocomplementemia) over specific SAD-related markers (anti-ENA antibodies, anti-dsDNA, anti-cyclic citrullinated peptide) in patients with HCV.Conclusion.In the selected cohort, the SAD most commonly reported in association with chronic HCV infection were SS (nearly half the cases), RA and SLE. Nearly two thirds of SAD-HCV cases were reported from the Mediterranean area. In these patients, ANA, RF and cryoglobulins are the predominant immunological features.
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Nossent, J., H. Keen, D. Preen, and C. Inderjeeth. "POS0751 TEMPORAL TREND IN HOSPITALISATION FOR OPPORTUNISTIC INFECTIONS IN PATIENTS WITH CONNECTIVE TISSUE DISEASES." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 661.1–661. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2552.
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BackgroundPatients with autoimmune connective tissue disease (CTD) and systemic vasculitis (SV) often require aggressive immune-modulating therapy to prevent organ damage. This however increases the risk for common and uncommon infections.ObjectivesTo compare the temporal rates and associated mortality of hospitalisation with opportunistic infections (OI) for CTD and SV patients in Western Australia between 1985 and 2015.MethodsAll patients hospitalized in Western Australia in the period 1985-2015 with ≥ 2 ICD based diagnostic codes for SLE (n=1432), other CTD (o-CTD; incl DM/PM, systemic sclerosis, Sjogren’s syndrome; n=2161) and Systemic vasculitis (SV; n=1599) and a microbiologically confirmed OI (Mycobacterial, Fungal and viral infections) were included. Descriptive data are given as median (IQR) and frequency (%). Incidence rates per 1000 person years (IR) were calculated during 100.410 person years.ResultsOI occurred in 12.4 % of lupus, 11.5% of SV and 10.4% of o-CTD patients (p=0.72), but overall IR rates for OI were higher for lupus patients (9.87, CI 5 .49-15.76) than for SV (5.94, CI-2.81-10.24) and o-CTD patients (3.40, CI 1.62-7.23). However, whereas the IR for OI in lupus decreased over time, the IR increased for SV and o-CTD patients (Figure 1). Viral infections were the most frequent specific OI followed by tuberculosis and mycotic infections. Cryptococcal infections were observed in lupus patients only and the limited cases of pneumocystis occurred predominantly in SV patients with no cases observed after 2000 (Figure 2). In hospital mortality during OI admission was 11.5% for SV, 5.6 % for lupus and 3.5% for o-CTD patients (p=0.004).Figure 1.Figure 2.ConclusionHospitalization rates for OI have decreased for lupus patients especially since 2005, whereas viral and mycotic OI rates have increased for both SV and o-CTD patients. Hospitalization for OI associated with significant case fatality in especially SV patients, indicating a need for increased prevention of OI.References[1]Esposito S, Bosis S, Semino M, Rigante D. Infections and systemic lupus erythematosus. Eur J Clin Microbiol Infect Dis. 2014 Sep;33(9):1467-75AcknowledgementsSupported by an unrestricted grant from The Arthritis Foundation of Western AustraliaDisclosure of InterestsNone declared
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White, Alice A., Ashleigh Lin, Xander Bickendorf, Blake S. Cavve, Julia K. Moore, Aris Siafarikas, Deborah H. Strickland, and Jonatan Leffler. "Potential immunological effects of gender-affirming hormone therapy in transgender people – an unexplored area of research." Therapeutic Advances in Endocrinology and Metabolism 13 (January 2022): 204201882211396. http://dx.doi.org/10.1177/20420188221139612.
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There are well-described sex-based differences in how the immune system operates. In particular, cisgender (cis) females have a more easily activated immune system; associated with an increased prevalence of autoimmune diseases and adverse events following vaccinations. Conversely, cis males have a higher threshold for immune activation, and are more prone to certain infectious diseases, such as coronavirus disease (COVID-19). Oestrogen and testosterone have immune-modulatory properties, and it is likely that these contribute to the sexual dimorphism of the immune system. There are also important immune-related genes located on the X chromosome, such as toll-like receptor (TLR) 7/8; and the mosaic bi-allelic expression of such genes may contribute to the state of immune hyperactivation in cis females. The scientific literature strongly suggests that sex-based differences in the functioning of the immune system are related to both X-linked genes and immune modulation by sex hormones. However, it is currently not clear how this impacts transgender (trans) people receiving gender-affirming hormonal therapy. Moreover, it is estimated that in Australia, at least 2.3% of adolescents identify as trans and/or gender diverse, and referrals to specialist gender-affirming care are increasing each year. Despite the improving social awareness of trans people, they remain chronically underrepresented in the scientific literature. In addition, a small number of case studies describe new onset autoimmune disorders in adult trans females following oestrogen use. However, there is currently minimal long-term research with an immunological focus on trans people. Therefore, to ensure the positive health outcomes of trans people, it is crucial that the role of sex hormones in immune modulation is investigated further.
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Almutairi, K., J. Nossent, D. Preen, H. Keen, and C. Inderjeeth. "SAT0576 THE PREVALENCE OF RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW OF POPULATION-BASED STUDIES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1246.2–1247. http://dx.doi.org/10.1136/annrheumdis-2020-eular.696.
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Background:Rheumatoid arthritis (RA) is a heterogeneous disease with unknown aetiology (1). The reported worldwide RA prevalence varies widely (2, 3), and it is unclear whether this is due to inconsistencies in defining populations or methodologies used to identify RA patients (3, 4). Accurate RA prevalence data are required to plan preventative, diagnostic, and management strategies to address raising health care service demands and costs associated with improved lifespan and level of disability (5, 6).Objectives:To estimate the prevalence of RA from international population-based studies and investigate the influence of prevalence definition, data sources, classification criteria and geographical area on RA prevalence.Methods:A systematic review of existing literature was performed using the Joanna Briggs Institute approach for the systematic review and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search of ProQuest, MEDLINE, Web of Science, and EMBASE was undertaken to include population-based studies investigating RA prevalence between 1980 and 2019.Results:Sixty published population-based studies met the inclusion criteria over the study period. The mean point-prevalence of RA was 0.56% (range 0.00% to 2.70%) between 1986 and 2014. The period-prevalence was 0.51% (range 0.05% to 1.9%) between 1955 and 2015. RA point- and period-prevalence was higher in urban settings than rural settings, (0.69% vs 0.48%) and (0.54% vs 0.25%), respectively. The mean point- and period-prevalence were 0.56% (SD=0.52) and 0.57% (SD=0.41) and were lower in sampling population studies than in larger population databases studies (0.60% (SD=0.27) and 0.44% (SD= 0.26)). The highest period-prevalence of RA was observed in linked databases (0.80%, SD=0.1) where RA diagnosis was validated by rheumatologists.Conclusion:The average point- and period-prevalence of RA were 51/10,000 and 56/10,000 respectively. The RA prevalence was higher in urban areas than rural areas, suggesting an impact of environmental differences. Population database studies were more consistent than sampling studies, and linked databases appeared to provide the best estimate of RA period-prevalence when rheumatologists clinically verified RA.Table 1.The top five countries for the highest and lowest prevalence of RA in recent global estimate between 1980 and 2019.Global prevalence of RATop five countriesPrevalence (%)Highest1-Cuba2.702-Finland1.903-Lesotho1.804-USA1.075-Lebanon1.00Lowest1-Nigeria0.002-Taiwan0.05Taiwan0.10Taiwan0.123-Thailand0.124-India0.155-Philippines0.17References:[1]Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018;4:1-23.[2]Tobon GJ, Youinou P, Saraux A. The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis. Journal of Autoimmunity 2010;35:10-4.[3]Shapira Y, Agmon-Levin N, Shoenfeld Y. Geoepidemiology of autoimmune rheumatic diseases. Nature reviews Rheumatology 2010;6:468-76.[4]Carmona L, Cross M, Williams B, Lassere M, March L. Rheumatoid arthritis. Best Pract Res Clin Rheumatol 2010;24:733-45.[5]Kvien TK. Epidemiology and burden of illness of rheumatoid arthritis. Pharmacoeconomics 2004;22:1-12.[6]Uhlig T, Moe RH, Kvien TK. The burden of disease in rheumatoid arthritis. Pharmacoeconomics 2014;32:841-51.Acknowledgments:Khalid Almutairi was supported by an Australian Government Research Training Program PhD Scholarship at the University of Western Australia (UWA).We acknowledge senior librarian Samantha Blake (SB) for her help within the scope of UWA library support services for systematic reviewers.Disclosure of Interests:Khalid Almutairi: None declared, Johannes (“Hans”) Nossent Speakers bureau: Janssen, David Preen: None declared, Helen Keen Speakers bureau: Pfizer Austrlaia, Abbvie Australia, Charles Inderjeeth Grant/research support from: UCB Australia, Speakers bureau: Eli Lilly
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Khalili, Ellie, Brent Venning, Mike Boggild, and Simon A. Broadley. "082 Real world experience of treating multiple sclerosis with alemtuzumab." Journal of Neurology, Neurosurgery & Psychiatry 89, no. 6 (May 24, 2018): A33.2—A33. http://dx.doi.org/10.1136/jnnp-2018-anzan.81.
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IntroductionAlemtuzumab is a highly effective therapy for multiple sclerosis that has a significant, but well-defined adverse event profile. We report cases treated since the commercial release of alemtuzumab at two centres in Queensland with the aim of comparing real-world experience with trial data.MethodsThis was a retrospective case note review of patients treated with alemtuzumab for multiple sclerosis since becoming commercially available in Australia. The two sites were the Gold Coast University Hospital and the Townsville Hospital. Demographic, clinical and MRI data were systematically collected from the available records at each site. De-identified aggregated data were analysed using descriptive statistics (mean (±SD), median (range)) and compared with phase III clinical trial data.Results104 cases treated with alemtuzumab were identified at the two sites. The median age at first treatment was 3817–55 years, slightly older than the trial populations (33 and 35 years) and two-thirds were female. The mean disease duration was 8.4 (±7.0) years, which is longer that seen in the trials (2.1 and 4.5 years). The median number of prior relapses was 31–12 with 1 (0–3) in the prior 2 years. The median number of prior treatments for MS was 1.5. The median follow up was 201–35 months. The median EDSS at time of first treatment was 2 (0–7) and at last follow up was 1.5 (0–7). At last follow up, 24/104 (23%) had improved, 61/104 (58%) were stable and 9/104 (9%) had worsened. Autoimmune adverse events were seen in 18/104 (17%) with autoimmune thyroid disease being the most common (13/104 (13%).ConclusionAlemtuzumab is an effective therapy for MS. Clinical outcomes in a real world setting were similar to those seen in phase III clinical trials. Autoimmune diseases occurred in a similar proportion to those seen in clinical trials.References. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: A randomised controlled phase 3 trial. Lancet2012;380(9856):1819–28.. Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: A randomised controlled phase 3 trial. Lancet2012;380(9856):1829–39.
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Ekiert, Halina, Joanna Świątkowska, Paweł Klin, Agnieszka Rzepiela, and Agnieszka Szopa. "Artemisia annua – Importance in Traditional Medicine and Current State of Knowledge on the Chemistry, Biological Activity and Possible Applications." Planta Medica 87, no. 08 (January 22, 2021): 584–99. http://dx.doi.org/10.1055/a-1345-9528.
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Abstract Artemisia annua (annual mugwort) is a species that has long been used in traditional Asian medicine, mainly Chinese and Hindu. The species is widespread and known as a medicinal plant not only in Asia but also in Europe, in both Americas, and Australia. The species has become a subject of particular interest due to the 2015 Nobel Prize awarded for detecting the sesquiterpene lactone artemisinin in it and proving its antimalarial activities. The raw materials obtained from this species are Artemisiae annuae folium and Artemisiae annuae herba. The leaves are a raw material in the Chinese Pharmacopoeia and Vietnamese Pharmacopoeia. Both raw materials are in the International Pharmacopoeia published by the WHO. The main components of these raw materials are mainly specific sesquiterpene lactones, essential oil, flavonoids, coumarins, and phenolic acids. In traditional Asian medicine, the species is used, for example, in the treatment of jaundice and bacterial dysentery, as an antipyretic agent in malaria and tuberculosis, in the treatment of wounds and haemorrhoids, and in viral, bacterial, and autoimmune diseases. Professional pharmacological studies conducted today have confirmed its known traditional applications and explain previously unknown mechanisms of its biological action and have also found evidence of new directions of biological activity, including, among others, anti-inflammatory, analgesic, antioxidant, antitumour, and nephroprotective activities. The species is of growing importance in the cosmetics industry.
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Bridgewater, S., J. Dawson, M. Ndosi, R. J. Black, J. T. L. Cheah, E. Dures, N. Ghosh, et al. "AB0834 DEVELOPMENT OF A CONCEPTUAL FRAMEWORK FOR A PATIENT REPORTED OUTCOME MEASURE TO CAPTURE PATIENTS’ PERCEPTIONS OF GLUCOCORTICOID THERAPY DURING TREATMENT FOR RHEUMATIC DISEASES." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1441.1–1441. http://dx.doi.org/10.1136/annrheumdis-2021-eular.164.
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Background:Glucocorticoids (GCs) are a key treatment for the autoimmune rheumatic diseases; however, they produce numerous physical and psychological side effects.1 The Outcome Measures in Rheumatology (OMERACT) Glucocorticoid Working Group have identified that there are no Patient Reported Outcome Measures (PROMs) for assessing the impact of systemic GC therapy across multiple rheumatic diseases from the patient’s perspective.2,3Objectives:The aim is to explore the impact of GCs on the symptoms and health-related quality of life of adults with rheumatic inflammatory diseases, to inform items for inclusion in a PROM. Key considerations will include patient perceptions of GC therapy at diagnosis and over the course of treatment, for use in future randomised controlled trials or in clinical practice.Methods:An international steering committee comprising researchers, rheumatology clinicians, methodologists and patient partners in the UK, Australia and USA developed an initial conceptual framework informed by a review of the literature. Semi-structured interviews were conducted in each country with patients who had an autoimmune rheumatic disease and had received GC therapy. The interviews explored salient aspects of health-related quality of life associated with being treated with GCs.Results:Interviews have been completed in three continents with patients who had a range of demographic features, rheumatological conditions and duration and dosage of GC therapy. Figure 1 shows the initial conceptual framework for developing the GC PROM (Steroid PRO).Figure 1.Conclusion:This conceptual framework will act as an evolving guide in the development of a PROM for assessing patients’ perspectives of systemic glucocorticoid therapy. Future work will include inductive analysis of qualitative transcripts to inform candidate questionnaire items, cognitive interviewing, linguistic translatability assessment, and an international validation survey to define the final PROM questionnaire and its measurement properties.References:[1]Cheah JTL, Robson JC, Black RJ, et al. The patient’s perspective of the adverse effects of glucocorticoid use: A systematic review of quantitative and qualitative studies. From an OMERACT working group. Semin Arthritis Rheum. 2020 Oct; 50(5):996-1005.[2]Black RJ, Robson JC, Goodman SM, et al. A Patient-reported Outcome Measure for Effect of Glucocorticoid Therapy in Adults with Inflammatory Diseases Is Needed: Report from the OMERACT 2016 Special Interest Group. J Rheumatol. 2017; 44(11):1754-8.[3]Cheah JTL, Black RJ, Robson JC, et al. Toward a Core Domain Set for Glucocorticoid Impact in Inflammatory Rheumatic Diseases: The OMERACT 2018 Glucocorticoid Impact Working Group. J Rheumatol. 2019; 46(9):1179-1182.Disclosure of Interests:Susan Bridgewater Grant/research support from: Grant from Vifor Pharma for an independent investigator-led study to develop a PRO for steroids, Jill Dawson: None declared, Mwidimi Ndosi: None declared, Rachel J Black: None declared, Jonathan T.L. Cheah: None declared, Emma Dures: None declared, Nilasha Ghosh: None declared, Elizabeth A Hoon: None declared, Iris Navarro-Millan Consultant of: Received consultant fees from SOBI, Diyu Pearce-Fisher: None declared, Pamela Richards: None declared, Carlee Ruediger: None declared, Christine Silverthorne: None declared, Joanna Tieu Grant/research support from: Vifor Pharma, Sarah Mackie Consultant of: Consultancy on behalf of institution for Roche/Chugai, Sanofi, AbbVie and AstraZeneca, Grant/research support from: Educational grant from Roche to attend EULAR2019, Susan Goodman: None declared, Catherine Hill: None declared, Joanna Robson Speakers bureau: Vifor Pharma for educational webinar, Grant/research support from: Grant from Vifor Pharma for an independent investigator-led study to develop a PRO for steroids
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Maen, Anton, and Ian Edwin Cock. "Inhibitory activity of Australian culinary herb extracts against the bacterial triggers of selected autoimmune diseases." Pharmacognosy Communications 5, no. 2 (March 18, 2015): 130–39. http://dx.doi.org/10.5530/pc.2015.2.4.
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Cooper, Nichola, Robert P. Numerof, Sandra Tong, and David J. Kuter. "Fostamatinib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA): A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Global Study." Blood 136, Supplement 1 (November 5, 2020): 1–3. http://dx.doi.org/10.1182/blood-2020-140469.
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Background. Warm antibody autoimmune hemolytic anemia (wAIHA) is a rare disorder that can be potentially serious. In wAIHA, autoantibodies react with protein antigens on red blood cells (RBCs) at body temperature, leading to RBC phagocytosis and destruction by Fcg receptor-bearing macrophages in a spleen tyrosine kinase (SYK) dependent signaling pathway (see figure). Fostamatinib is a potent oral SYK inhibitor, approved for the treatment of chronic immune thrombocytopenia (ITP). Fostamatinib prevents platelet destruction in ITP through inhibition of SYK-dependent platelet phagocytosis by Fcγ receptor-bearing macrophages. Fostamatinib was evaluated in a phase 2, open-label, multicenter study (NCT02612558) for the treatment of wAIHA. Results of the study demonstrated that 11 of 25 (44%) patients had markedly improved hemoglobin (Hgb) levels after fostamatinib treatment. Adverse events (AEs) were consistent with those in the fostamatinib safety database of >4000 patients across multiple diseases. Based on the results of the phase 2 study, a phase 3 randomized, double-blind, placebo-controlled, global study (NCT03764618) was initiated to investigate the safety and efficacy of fostamatinib in patients with wAIHA. The phase 3 study began enrolling patients this year and intends to enroll approximately 90 patients at 103 sites in 22 countries across North America, Europe, and Australia. This is the first randomized, double-blind, placebo-controlled, phase 3 study to evaluate a SYK inhibitor for the treatment of wAIHA (see diagram). Study Design and Methods Inclusion Criteria include: Age ≥18;Diagnosis of primary or secondary wAIHA (documented by an IgG or IgA positive direct antiglobulin test [DAT]);failure of ≥1 prior treatment for wAIHA;Haptoglobin <LLN (lower limit of normal) or total bilirubin >ULN (upper limit of normal) or lactate dehydrogenase (LDH) >ULN;Baseline hemoglobin level ≤9 g/dL or, if hemoglobin is >9 g/dL to <10 g/dL, subject must be on a permitted wAIHA treatment AND have symptoms associated with anemia. Exclusion Criteria include: Presence of other forms of AIHA;Uncontrolled or insufficiently controlled hypertension;Neutrophil count <1,000/µL,Platelet count <30,000/μL (unless patient has Evans syndrome);Transaminase levels >1.5 x ULN. Eligible patients will be randomized 1:1 to fostamatinib or placebo for 24 weeks. Randomization will be stratified by concomitant steroid use and severity of anemia at baseline. The starting dose of fostamatinib is 100 mg BID and will be increased to 150 mg BID at Week 4, based on tolerability. The dose may be reduced in the event of dose-limiting AEs. At screening, patients may continue selected concurrent wAIHA therapies including steroids (maximum of 2 therapies) throughout the 24-week study period. A steroid taper protocol will allow reduced used of steroids in patients who have a hemoglobin response. Rescue therapy will be allowed as needed. Patients who complete the phase 3 study can rollover to an open-label extension study. The efficacy endpoints will include hemoglobin response, defined as a hemoglobin level ≥10 g/dL with a ≥2 g/dL increase from baseline (Day 1) in the absence of rescue therapy; duration of hemoglobin response; and the need for wAIHA rescue treatment. The safety endpoints will include the incidence of adverse events. Patients will be evaluated in the clinic, including safety and laboratory assessments, at two-week intervals. Statistics: A sample size of 90 subjects (randomized 1:1) would be required to provide 80% power to detect a difference in the response between the active and placebo groups using the Cochran-Mantel-Haenszel test at a two-sided significance level of 0.05 (based on results of the phase 2 study). The response rate will be compared between groups using a chi-square test adjusted for randomization stratification factors. Current enrollment status: As of July 2, 2020, 83 sites are open to screening (subject to local regulations about the COVID-19 pandemic), and 43 patients have been randomized. Most patients (88%) had primary wAIHA, 12% had secondary disease including chronic lymphocytic leukemia, monoclonal B cell lymphocytosis, scleroderma, smoldering Waldenström's macroglobulinemia, and systemic lupus erythematosus in 1 patient each. The median age at baseline is 61 years (range 28-87), and 63% are female. Figure Disclosures Cooper: Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Numerof:Rigel: Current Employment, Current equity holder in publicly-traded company. Tong:Rigel: Current Employment, Current equity holder in publicly-traded company. Kuter:Incyte: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Immunovant: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Dova: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Up-To-Date: Consultancy, Honoraria, Patents & Royalties; Zafgen: Consultancy, Honoraria; Sanofi (Genzyme): Consultancy, Honoraria; Shionogi: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Principia: Consultancy, Research Funding; Protalix Biotherapeutics: Consultancy; Shionogi: Consultancy; Actelion (Syntimmune): Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Agios: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Alnylam: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Argenx: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Immunovant: Other: Travel Expenses, Research Funding; Caremark: Consultancy, Honoraria; CRICO: Consultancy, Honoraria; Kezar Life Sciences, Inc: Other, Research Funding; Principia Biopharma: Consultancy, Honoraria, Other, Research Funding; Protalex: Consultancy, Honoraria, Other, Research Funding; Rigel: Consultancy, Honoraria, Other, Research Funding; Takeda (Bioverativ): Consultancy, Honoraria, Other, Research Funding; Protalex: Consultancy, Honoraria, Research Funding; Kyowa-Kirin: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Platelet Disorder Support Association: Consultancy, Honoraria.
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Maen, Anton, and Cock I E. "Inhibitory activity of high antioxidant Australian native fruits against the bacterial triggers of selected autoimmune diseases." Pharmacognosy Communications 5, no. 1 (December 16, 2014): 64–74. http://dx.doi.org/10.5530/pc.2015.1.5.
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Ratnasingam, Sumita, Patricia A. Walker, Huy Tran, Zane Kaplan, James David McFadyen, Huyen Tran, Tse-Chieh Teh, et al. "Bortezomib Yields High Response Rates in Antibody-Mediated Autoimmune Hematological Diseases Refractory to Conventional Immunosuppression." Blood 126, no. 23 (December 3, 2015): 3457. http://dx.doi.org/10.1182/blood.v126.23.3457.3457.
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Abstract Introduction Certain patients with antibody-mediated autoimmune disease exhibit poor responses to conventional immunosuppression. Proteasome inhibitors (PI) have been prospectively evaluated in humoral graft rejection, where rapid alloantibody depletion occurs in the context of combined immunosuppression. In addition to killing antibody-producing cells, PIs deplete autoreactive T-cells, suppress inflammatory NFkB signaling and modulate MHC class I antigen presentation. The durability of rituximab-based B-cell depletion may be abrogated by promotion of long-lived autoreactive (CD20 neg) plasma cell development. Therefore there is a strong rational for utilising PIs in antibody mediated autoimmune disease. Based on our initial experience re-purposing bortezomib (BTZ) to deplete ADAMTS-13 antibodies in thrombotic thrombocytopenic purpura (TTP) (Shortt et al NEJM 2013; 69: 90-2.), we have utilized off-label BTZ in cases of severe refractory antibody-mediated hematological disease via a compassionate access program. We report the first case-series of BTZ use in this broader patient group. Patients & Methods Outcome data were collected for all patients treated between 2012 and 2015 with off-label BTZ salvage for autoantibody-mediated hematological disease across a combined health-care network in the Australian state of Victoria (catchment area >1.5 million patients; 3 major academic centers). Eligible patients were refractory to standard of care and at risk of severe morbidity/mortality from underlying disease or immunosuppression. All patients demonstrated on-going autoantibody production despite rituximab-based B-cell depletion. We sought to correlate biological responses (e.g. reductions in autoantibody titer) with clinical efficacy (e.g. remission rates and capacity to wean concurrent immunosuppression) and to document BTZ toxicities. Compassionate BTZ access was subject to institutional drug and therapeutic committee review and Australian Therapeutic Goods Administration notification. Routine antiviral prophylaxis was administered. Results: Treatment episodes (n=8) included TTP (n=3), warm autoimmune hemolytic anemia (AIHA) (n=3), cold AIHA (n=1) and an acquired FVIII inhibitor (n=1) in 7 patients (median age 53 years, range 34-80; M/F 4:3). Patients had received a median of 3.5 prior lines of therapy (range: 2-6) and all were rituximab exposed. BTZ was predominantly administered at 1.3mg/m2; D1, 4, 8, 11 q21d, with subsequent dose modification to weekly where repeated cycles were required. Initial IV therapy was preferred in TTP patients, to maximize exposure between exchanges; where recurrent cycles were administered all patients transitioned to subcutaneous administration to avoid neurotoxicity. With a median follow-up of 10 months (censored June 2015; range: 4-35 months), the overall response rate was 75%, including 50% durable complete remissions and 25% partial remission with reductions in transfusion requirements and baseline immunosuppression. Biological responses correlated with reductions in autoantibody titer. Most patients demonstrated an immediate response within 1 cycle (median cycles delivered 1.5; range: 1-6). BTZ was generally well tolerated with grade 4 hepatotoxicity observed in one patient in the context of high alcohol intake. No infective complications or neuropathy were observed. Table 1.CaseAgeM/FDiseasePrior Lines of TreatmentCyclesResponseDuration of response170MAIHA (warm)31NR02a53FTTP41CR7m2b54FTTP21CR25m364FAIHA (cold)56PR5m449FTTP21CR32m534MHemophilia A34CR4m647MAIHA (warm)52PR2m780MAIHA (warm)62NR0NR - no response; CR - complete response; PR - partial response (reduction in immunosuppression or disease activity) Conclusions: BTZ rapidly downregulates autoantibodies, correlating with a high response rate in relapsed/refractory autoimmune hematological disease with an acceptable/expected toxicity profile. This case series, taken together with emerging case reports of efficacy provide 'proof of concept' for the utility of PI in antibody mediated autoimmune disease. A prospective clinical trial protocol is in development. Disclosures Off Label Use: The drug to be discussed is bortezomib and its use in managing refractory autoimmune haematological disorders (off label use). Catalano:Celgene, Roche, Gilead: Honoraria. Opat:Janssen Pharmaceuticals: Other: Provision of subsidized medications only. Shortt:Janssen Pharmaceuticals: Other: Provision of subsidized medications only.
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Cooper, Nichola, Isabel Gorham, Ann M. Lowe, Robert P. Numerof, Sandy Tong, and David J. Kuter. "Trial in Progress: Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Global Study of Fostamatinib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia." Blood 134, Supplement_1 (November 13, 2019): 4800. http://dx.doi.org/10.1182/blood-2019-126544.
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Background. Warm antibody autoimmune hemolytic anemia (wAIHA) is a rare and potentially serious disease in which autoantibodies bind to red blood cells (RBCs), leading to phagocytosis by Fc receptor-bearing macrophages via a spleen tyrosine kinase (SYK) dependent signaling pathway. Fostamatinib is a potent SYK inhibitor that is orally administered and was approved for the treatment of chronic ITP in April 2018 by the US FDA and has demonstrated activity in patients with wAIHA. A phase 2, open-label, multicenter study (NCT02612558) showed that 11 of 25 (44%) patients with wAIHA had markedly improved hemoglobin (Hgb) levels after treatment with fostamatinib. Adverse events (AEs) from the phase 2 studies in wAIHA were manageable and consistent with those in the fostamatinib safety database of >3500 patients across multiple disease states. Therefore, the phase 2 results support the conduct of a phase 3 study in wAIHA. A phase 3, randomized, double-blind, placebo-controlled global study (NCT03764618) to investigate the safety and efficacy of fostamatinib in subjects with wAIHA is currently enrolling patients. The study intends to enroll approximately 80 patients at 109 sites in 19 countries across North America, Europe and Australia. This is the first randomized, double-blind, placebo-controlled study to explore the effect of a SYK inhibitor in the treatment of wAIHA. Study Design and Methods Inclusion Criteria: Eligible adult patients must have: primary or secondary wAIHA, documented by IgG or IgA positive direct antiglobulin test (DAT); failed ≥1 prior treatment for AIHA; haptoglobin <LLN (lower limit of normal) or total bilirubin >ULN (upper limit of normal) or lactate dehydrogenase (LDH) >ULN; and baseline hemoglobin level ≤9 g/dL or, if hemoglobin is >9 g/dL to <10 g/dL, subject must be on an allowed wAIHA treatment AND have symptoms related to anemia. Exclusion Criteria: Patients should not have other types of AIHA, uncontrolled or poorly controlled hypertension, a neutrophil count <1,000/µL, platelet count <30,000/μL (unless due to Evans syndrome), or transaminase levels >1.5 x ULN. Treatment: Patients will be randomized 1:1 to receive fostamatinib or placebo for 24 weeks. Patients will receive an initial dose of 100 mg BID which will be increased to 150 mg BID at Week 4, based on patient tolerability. In the event of dose-limiting AEs, the dose may be reduced at any time. Randomization will be stratified by concomitant steroid use at baseline and severity of anemia at screening. All patients will be allowed to continue concurrent steroid therapy and other selected wAIHA therapy (maximum of 2) throughout the 24-week study. A rescue medication protocol is allowed as needed. A steroid taper protocol allows reduced used of steroids in responsive patients. Patients who complete the phase 3 study will be encouraged to enroll in an open-label extension study to receive fostamatinib. Endpoints: Efficacy endpoints will include hemoglobin response, defined as a hemoglobin level >10 g/dL with a ≥2 g/dL increase from baseline (Day 1) in the absence of rescue medication; duration of hemoglobin response; and use of wAIHA rescue therapy. Safety endpoints include the incidence of adverse events. Patients will be evaluated at clinic visits approximately every two weeks for safety assessments and measurement of hemoglobin levels. Statistics: Based on results of the phase 2 study, a sample size of 80 subjects (randomized 1:1) would be required to provide 80% power to detect a difference in the response between the active and placebo groups using the Cochran-Mantel-Haenszel test at a two-sided significance level of 0.05. The response rate will be compared between groups using a chi-square test adjusting for randomization stratification factors. Figure Disclosures Cooper: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Gorham:Rigel: Employment, Equity Ownership. Lowe:Rigel: Consultancy. Numerof:Rigel: Employment, Equity Ownership. Tong:Rigel: Employment, Equity Ownership. Kuter:Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Protalix: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria; Dova: Consultancy, Honoraria; Agios: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Alnylam: Consultancy, Honoraria, Research Funding; Argenx: Consultancy, Honoraria, Research Funding; Shinogi: Consultancy, Honoraria; Platelet Disorder Support Association: Consultancy, Honoraria; Principia: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Kyowa-Kirin: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Shinogi: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Zafgen: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Principia: Consultancy, Honoraria, Research Funding; Protalex: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; Platelet Disorder Support Association: Consultancy, Honoraria; Kezar: Research Funding; Pfizer: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Caremark: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Protalix: Consultancy, Honoraria; Dova: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Protalex: Consultancy, Honoraria, Research Funding; Momenta: Consultancy, Honoraria; Kezar: Research Funding; Pfizer: Consultancy, Honoraria; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Alnylam: Consultancy, Honoraria, Research Funding; Argenx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Caremark: Consultancy, Honoraria; Zafgen: Consultancy, Honoraria; Shire: Consultancy, Honoraria. OffLabel Disclosure: Fostamatinib is a tyrosine kinase (SYK) inhibitor for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. The use of fostamatinib in other diseases is off-label.
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Cram, D. S., N. Fisicaro, L. J. McNeilage, R. L. Coppel, and L. C. Harrison. "Antibody specificities of Thai and Australian scleroderma sera with topoisomerase I recombinant fusion proteins." Journal of Immunology 151, no. 12 (December 15, 1993): 6872–81. http://dx.doi.org/10.4049/jimmunol.151.12.6872.
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Abstract Autoantibodies that react with the nuclear enzyme topoisomerase I (Topo I) are used as a diagnostic marker of diffuse scleroderma. To better define immune reactivity to Topo I, antibody epitopes in two patient populations were analyzed using recombinant Topo I proteins. Two overlapping partial cDNA clones encoding the complete amino acid sequence of Topo I were isolated from human placenta. Using the polymerase chain reaction, specific regions of Topo I were amplified and cloned into the pGEX expression vectors. To map Topo I epitopes, recombinant fusion proteins were analyzed by immunoblotting with 66 anti-Topo I sera from Thai and Australian patients with diffuse scleroderma. Six distinct epitope regions were identified along the length of the 765 amino acid enzyme. Almost all sera contained antibodies that recognized the midregion of Topo I (amino acids 453-560), as well as antibodies to one of more of the other epitope regions. Sixty percent of the sera contained antibodies that recognized a COOH-terminal epitope region (amino acids 658-765) encompassing the active site of the enzyme. This subset of Topo I antibodies could be responsible for the inhibition of enzymatic activity previously reported in vitro. Heterogeneous patterns of reactivity with the six Topo I epitope regions were observed, although over half the sera could be assigned to one of six distinct patterns. In general, antibodies in the Thai sera reacted more strongly with the six epitope regions. Furthermore, two of the epitope regions reacted exclusively with Thai sera, suggesting a degree of racial or geographical specificity in the autoantibody response to Topo I. The identification of multiple epitopes in Topo I conforms with the polyclonal autoantibody response to intracellular Ag found in other multisystem autoimmune diseases and is presumed to be driven by the presentation of multiple peptides from Topo I itself.
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Hong, Lih En, Deepak Singhal, Amilia Wee, Rakchha Chhetri, Mihir D. Wechalekar, Susanna Proudman, and Devendra K. Hiwase. "The Mutation Profile of Myelodysplastic Syndrome Associated with Auto-Immune Rheumatological Disorders." Blood 132, Supplement 1 (November 29, 2018): 3081. http://dx.doi.org/10.1182/blood-2018-99-119965.
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Abstract Introduction: A subset of patients with MDS and related myeloid disorders present with concomitant autoimmune rheumatological diseases (AIRD); however the prevalence ranges from 10-48% based on limited literature. Further, use of immunosuppressive agents in AIRD patients could confound the secondary diagnosis of MDS and in some cases cause it (therapy-related myeloid neoplasm; t-MN). The prevalence of cytopenia in AIRD patients is unknown and the genetic characteristics of MDS patients with concomitant AIRD have not been described. Hence, we interrogated two large multi-institutional databases -Royal Adelaide Hospital Rheumatology Database (RAH-RD) and South-Australian MDS (SA-MDS) registry in this study. Methods: Demographic, clinical, laboratory and treatment data of 2663 AIRD and 1157 MDS patients were analysed. In AIRD patients (autoimmune inflammatory arthritis, spondyloarthritis, vasculitis and connective tissue diseases), cytopenia (persisting >6 months) were defined as follows: hemoglobin <100g/dL, absolute neutrophil <1800/mm3 and platelet <100,000/mm3. Targeted massively parallel sequencing of a custom panel of 43 myeloid neoplasms associated genes and 20 Fanconi (FA) DNA repair pathway genes (all coding regions) was performed on diagnosis bone marrow samples (n=237). An in-house well established filtering pipeline was used for identification of somatic mutations. Matched germline material was available for 62/194 (32%) patients. Only variants with Genome Aggregation Database minor allele frequency of ≤0.01% and variant allele frequency of ≥35% were selected for further analysis of germline variants. Results: During follow up of 2663 AIRD patients, 36 (1.3%) patients satisfied the criteria for at least one cytopenia. Anemia (19/36, 53%) was most common followed by neutropenia (8/36, 22%), thrombocytopenia (4/36, 11%) and bi-cytopenia (5/36, 14%). Twenty-two patients had bone marrow examination which was non-diagnostic in 16 patients, while 7/2663 (0.3%) patients were diagnosed with MDS. Importantly, 5 patients with MDS and 11 patients with cytopenia did not receive any cytotoxic agents. In the MDS database, 69(5.4%) were diagnosed with AIRD, with rheumatoid arthritis (n=20, 29%) being the most common AIRD. Among these 69 patients, 24 (34.8%) had low risk MDS and 15 (21.7%) had higher risk MDS. The remaining 30 patients had t-MN (n=19, 27.5%), MDS/MPN (n=8, 11.6%) and AML (n=3, 4.3%). Overall, in a combined population of 2663 RAH-RD and 1157 SA-MDS, 76(2%) had concomitant MDS and AIRD. Genetic profile of patients with MDS and AIRD: The cytogenetic and mutational profile of MDS patients with (n=20) or without (n=217) AIRD were compared. No significant difference was seen in the cytogenetic profile (normal, complex or monosomal karyotype, chr. 5 or 7 abnormalities) between the two groups but in mutational analysis, 56 mutations were seen in 20 MDS patients with AIRD (Fig1). In these patients, mutations in epigenetic pathways were most common (23/56, 41%) followed by transcription pathway (10/56, 18%). Splicing mutations were seen in 5 patients, with SRSF2 mutations being more common than SF3B1. Mutations in TP53 were present in 4 (24%) patients; 3/4 patients developed MDS following therapy for AIRD (t-MDS). IDH1 mutations were found in significantly higher frequency in MDS patients with AIRD compared to MDS without AIRD (30% vs 3%, p=0.04). There was no significant difference in the frequency of other mutations or overall mutation frequency between the two groups. Interestingly, 2 (10%) patients with MDS and AIRD also had rare, deleterious germline mutations in FA pathway genes (BRCA2 V2601M and L2512F) which could suggest either genetic predisposition to both these conditions or compromised DNA repair capability increasing susceptibility to t-MN. Conclusions: In a large multi-institutional cohort of autoimmune rheumatological disorders, 1.3% patients developed persistent cytopenia with 0.3% diagnosed with MDS. This is significantly higher than incidence of MDS in the general population (30-50/100,000). Similarly, 5% MDS patients had AIRD. The mutation profile of MDS patients with AIRD shows higher frequency of IDH1 and SRSF2 mutations. A small proportion of cases also had deleterious rare germline mutations in the DNA repair pathway. Our findings warrant further study and have potential implications for selection of immunosupressive agents for AIRD. Disclosures Hiwase: Novartis: Research Funding; Celgene: Research Funding.
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Singhal, Deepak, Christopher N. Hahn, Cassandra M. Hirsch, Amilia Wee, Monika M. Kutyna, Milena Babic, Rakchha Chhetri, et al. "Genetic Predisposition to Therapy-Related Myeloid Neoplasm By Rare, Deleterious Germline Variants in DNA Repair Pathway and Myeloid Driver Genes." Blood 132, Supplement 1 (November 29, 2018): 1802. http://dx.doi.org/10.1182/blood-2018-99-117815.
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Abstract Therapy-related myeloid neoplasm (t-MN) is considered to be a direct stochastic complication of chemotherapy and/or radiotherapy for primary cancer or autoimmune diseases. However, genetic predisposition is reported in 8-12% of sporadic adult cancer patients [Lu et al Nature Communication 2015 and Huang et al Cell 2018]. Similarly, genetic predispositions to t-MN have also been reported in limited single institute studies of small numbers of patients [Churpek et al Cancer 2016]. In this study, we performed comprehensive germline and somatic mutation profiling in t-MN using next generation sequencing. Matched germline material was available for 62/194 (32%) patients. Mutation profiling was correlated with clinical features including family history in 194 patients enrolled in the South Australian MDS (SA-MDS) registry and Cleveland Clinic (CC). An in-house well established filtering pipeline was used for identification of somatic mutations. Only variants with Genome Aggregation Database (gnomAD) minor allele frequency (MAF) of ≤0.01% and variant allele frequency (VAF) of ≥35% were selected for further analysis of germline variants. Variants reported in in the Catalogue of Somatic Mutations in Cancer database and MDS/AML were excluded from further analysis. Variants reported pathogenic in Breast Cancer Information Core (BIC) database and Leiden Open Variation Database (LOVD) were retained. Other variants were included if truncating (nonsense, indels, splice alterations), CADD>20, or predicted deleterious by >4/6 scoring algorithms (GERP>4, PhyloP>2, SIFT, PolyPhen2, MutationTaster and FATHMM). Forty-one (21%) t-MN patients harbored 45 rare (MAF<0.001) and deleterious germline mutations in the Fanconi anaemia (FA) pathway and driver myeloid genes including frameshift indels and splice site alterations in BRCA1, BRCA2, FANCA, PALB2, RAD51, DDX41 and TP53 (Figure 1A-B). The highest number of FA germline variants were seen in BRCA1 and FANCA (n=5 each) followed by BRCA2 (n=4), ERCC4, PALB2 and FANCC (n=2 each). We also identified 14 rare, deleterious myeloid germline variants in 13/194 (6.7%) of t-MN patients. These germline myeloid variants were identified in TP53, DDX41, GATA2 and MET; genes with well-known drivers of myeloid malignancies. Of the five acute lymphoblastic leukaemia patients with t-MN, 2/5 (40%) had rare myeloid germline variants in TP53, GATA2 and KMT2A. The frequency of these germline mutations in our t-MN cohort is higher than in the general population (gnomAD; Table 1) and in patients with primary malignancies such as breast cancer and lymphoma [Lu et al Nature Communication 2015 and Churpek et al Cancer 2016]. Intriguingly, the frequency of germline FA gene mutations (FAMT) in our therapy-related myelodysplastic syndrome (t-MDS) patients is also higher than those reported in primary MDS patients (18% vs 9%, p=0.02) [Przychodzen et al 2018]. Additionally, of those with available family history, 62% of t-MN patients have first and/or second degree relatives with non-skin cancers. Significantly more patients with FA mutation (FAMT) had first and second degree relatives with cancers compared to patients without FA (FAWT) mutations (82% vs 58%; p=0.03). Additionally, chromosomes 3 and 7 abnormalities, as well as monosomal karyotype, were more frequent in FAMT cases compared to FAWT. Similarly, somatic mutations in GATA2 (10% vs 2%; p=0.02), BCOR (13% vs 4%; p=0.03) and IDH2 (10% vs 2%; p=0.02) were more frequent in FAMT compared to FAWT cases (Figure 1C). In summary, we show that at least one in five t-MN patients harbor deleterious germline mutations, and 82% of FAMT patients have a first or second degree relative with cancers. These findings have implication in management of not only t-MN patients but genetic testing for their family members. Disclosures Branford: Qiagen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cepheid: Honoraria. Maciejewski:Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ra Pharmaceuticals, Inc: Consultancy; Apellis Pharmaceuticals: Consultancy; Apellis Pharmaceuticals: Consultancy. Hiwase:Celgene: Research Funding; Novartis: Research Funding.
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Cowan, Timothy L., Cheng Huang, and Dédée F. Murrell. "Autoimmune blistering skin diseases triggered by COVID-19 vaccinations: An Australian case series." Frontiers in Medicine 9 (January 10, 2023). http://dx.doi.org/10.3389/fmed.2022.1117176.
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Autoimmune blistering skin diseases (AIBD) can be induced or flared by a multitude of sources, however, there have been some reports suggesting that this occurrence is due to COVID-19 vaccinations. At a single academic blistering disease centre in Sydney, Australia, a retrospective review was conducted, identifying 59 patients with AIBD seen between February 2021 and November 2022. Secondary to recent COVID-19 vaccination, four patients had induction of bullous pemphigoid, three patients had a flare of pre-existing bullous pemphigoid, one patient had induction of pemphigus, and two patients had a flare of pre-existing pemphigus vulgaris. This adds to our understanding of the role of vaccinations in the activity of AIBD.
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"Bioboard." Asia-Pacific Biotech News 11, no. 21 (November 15, 2007): 1393–98. http://dx.doi.org/10.1142/s0219030307001516.
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AUSTRALIA — Scientists Find Genetic Key to Autoimmune Diseases. AUSTRALIA — Funding Awarded to Starpharma and Baker Heart Research Institute to Develop Arterial Disease Imaging Agent. AUSTRALIA — Gene Syndrome Behind a Significant Number of Endometrial Cancers. CHINA — Breast Cancer Leading Cause of Death Among Local Women in China. CHINA — Chinese Government Encourages the Practice of TCM. CHINA — Unified Code Name System for Drugs Set for Year-End Launch. JAPAN — Researchers at Japanese National Institute for Physiological Sciences Discover Brain Compensatory Mechanisms that Enhance the Recovery from Spinal Cord Injury. TAIWAN — Academia Sinica Opens Its Mutant Mouse Lab Facilities. THAILAND — The Cause of Recent Sustained Outbreak of Human Leptospirosis in Thailand Discovered. SINGAPORE — Singapore's NCCS Finds New Cure for Advanced Colon Cancer Patients. SINGAPORE — Protein Found to Turn On Genes Related to Obesity.
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Seviiri, Mathias, Matthew H. Law, Jue-Sheng Ong, Puya Gharahkhani, Pierre Fontanillas, Stella Aslibekyan, Adam Auton, et al. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma." Nature Communications 13, no. 1 (December 10, 2022). http://dx.doi.org/10.1038/s41467-022-35345-8.
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AbstractBasal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.
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Farouk Allam, Mohamed. "Maivel Emile Soby Gerges, Ghada Essam Aldin, Diaa Marzouk Abdel Hamid and Mohamed Farouk Allam*." Public Health Open Access 3, no. 2 (2019). http://dx.doi.org/10.23880/phoa-16000138.
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Vitamin D deficiency is a common public-health problem. Deficiency is more common in women than men, and the childbearing period is known to represent a particularly high-risk situation. High rates of poor vitamin D status are found among women during the childbearing period throughout the world. Women at reproductive age are a group that can be susceptible at earlier age for vitamin D deficiency and its complications as increase the risk of osteopenia, osteoporosis, muscle weakness, osteomalacia and pathological fractures and can worsen other chronic conditions, such as the polycystic ovary syndrome; it is also a risk factor for cardiovascular diseases, metabolic syndrome, some types of cancers and some autoimmune diseases. Several studies have identified a surprisingly high prevalence of vitamin D deficiency in all age groups such as in Europe after 14 population study, United States, Canada and Australia. Despite reported prevalence of vitamin D deficiency and insufficiency depend on the cut-off values used that vary between studies, an estimated 1 billion people worldwide have vitamin D deficiency or insufficiency or hypovitaminosis D. National surveys should be conducted in every country to determine normal levels of vitamin D in that country and the need for national screening programs for vitamin D deficiency.
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Wilkinson, Michael, Kathy Cash, Bernice Gutschmidt, Sophia Otto, and Vidya Limaye. "Secondary myoadenylate deaminase deficiency is not a common feature of inflammatory myopathies: A descriptive study." Frontiers in Medicine 9 (November 23, 2022). http://dx.doi.org/10.3389/fmed.2022.1061722.
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BackgroundMyoadenylate deaminase (MAD) deficiency is a form of metabolic myopathy, which generally causes only mild symptoms in the primary inherited form. Inflammatory myopathies are a group of autoimmune diseases which result in skeletal muscle weakness. In addition to inflammatory pathology, it has been speculated that non-inflammatory mechanisms, and possibly secondary MAD-deficiency, may potentially contribute to weakness in these conditions.MethodsWe investigated for an association between these two myopathic processes through two complementary methods. Firstly, muscle biopsy records in South Australia over a 17-year period were retrospectively reviewed for diagnosis of myositis or MAD-deficiency, as well as associated clinical features. Secondly, a prospective arm histochemically tested all incident biopsy specimens over a 12-month period for MAD-deficiency.ResultsIn the retrospective arm, 30 MAD-deficient cases were identified (1.3% of all biopsies), with no significant difference observed in overall rates of myositis diagnosis between patients with intact and deficient MAD activity (21.3% vs 26.7%, P = 0.47). No cases of MAD-deficiency were detected in the prospective arm, despite 39 cases of myositis being identified over this period.ConclusionSecondary MAD deficiency is unlikely to be a major driver of symptoms in inflammatory myopathies.
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Khoo, Thomas, Navkiran Sidhu, Franca Marine, Susan Lester, Alannah Quinlivan, Debra Rowett, Rachelle Buchbinder, and Catherine L. Hill. "Perceptions towards biologic and biosimilar therapy of patients with rheumatic and gastroenterological conditions." BMC Rheumatology 6, no. 1 (December 23, 2022). http://dx.doi.org/10.1186/s41927-022-00309-4.
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Abstract Background Biologic and targeted synthetic disease modifying agents (b/tsDMARDs) have broadened the treatment landscape for autoimmune diseases particularly in patients refractory to conventional DMARDs. More recently, the introduction of biosimilars has reduced the price of bDMARDs, potentially improving accessibility. Though efficacy and safety have been described, patient attitudes to b/tsDMARDs are not well-understood. We aim to investigate patients’ beliefs about biologic and biosimilar therapy, and the factors influencing their perceptions. Methods Patient consumer groups (Arthritis Australia, Crohn’s and Colitis Australia) assisted in advertising an online questionnaire for people with a self-reported diagnosis of inflammatory arthritis (IA) or inflammatory bowel disease (IBD). The questionnaire incorporated the Belief about Medicines Questionnaire (BMQ) and the single-item literacy screener (SILS). Sources and favourability of biologic/biosimilar information were analysed, using the chi-square and a non-parametric trend test for unordered and ordered categorical variables respectively, comparing respondents with IA and IBD. Results Eight hundred and thirty eight people (686–IA, 144–IBD, 8 both) responded. 658 (79%) used b/tsDMARDs. The BMQ demonstrated high necessity belief (median 4.2) with moderate concerns (median 2.8) about biologics. 95% of respondents obtained medication information from specialists though most used multiple sources (median 4). The most positive resources were specialists and specialist nurses. 73/141 (52%) respondents with IBD obtained information from specialist nurses compared with 202/685 (29%) with IA (p = 0.012). Respondents with limited reading ability on SILS were more likely to discuss information with a general practitioner or pharmacist. Younger respondents and those with higher BMQ concern scores more frequently consulted less reliable sources (e.g. social media). 502 respondents (60%) answered the biosimilar questions. Only 23 (4.6%) reported currently using a biosimilar and 336 (66.9%) were unsure if biosimilars were available in Australia. Specialist recommendation was the most frequent factor that would influence a patient to change from originator to biosimilar (352/495, 71.1%). Conclusions There is a high level of trust in specialists’ recommendations about b/tsDMARDs, although most people also utilise additional information sources. Contextual factors influencing resource selection include age, reading ability and degree of concern about medicines. People with IA and IBD have similar attitudes though those with IBD more frequently access specialist nurse advice.
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Yeo, Ai Li, Michelle Leech, Samar Ojaimi, and Eric Morand. "Utility of repeat extractable nuclear antigen antibody testing- a retrospective audit." Rheumatology, August 2, 2022. http://dx.doi.org/10.1093/rheumatology/keac437.
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Abstract Objectives Autoantibodies to extractable nuclear antigens (ENA) are frequently ordered during the workup of suspected autoimmune connective tissue diseases. There are no current guidelines for repeat test ordering. The objective of this study was to assess the utility of repeat ENA testing after an initial negative result. Methods A retrospective study was conducted in a single, multicentre tertiary health network in Melbourne, Australia. Results of all ENA tests were extracted from the hospital laboratory information system. For patients who had a change in ENA result from negative to positive, clinical information was obtained from the hospital records regarding new diagnosis of an antinuclear antibody (ANA)-associated rheumatic disease (AARD). Results A total of 23 438 ENA tests were performed in 19 603 patients from 29th July 2013 to 28th September 2020. 20 918 (89.2%) were negative with 215 (0.9%) being equivocal. Of the 2,305 positive tests, the most common ENA auto-antibody specificity detected was anti-Ro52 (1,185, 51.4%). 2,636 of 19 603 patients (13.4%) had more than one ENA test performed during the study period. Of these, most (2,523, 95.7%) had stable ENA results with no change compared with the first test. Only 53 patients (2.2%) had an ENA result that changed from negative to positive. Excluding patients with pre-existing rheumatic conditions and those under 18, there were five new AARD found in the remaining 34 patients. Conclusion Repeat ENA test results rarely change or result in a new diagnosis of an AARD, with repeated testing only warranted if there is a change in clinical manifestations.
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Lee, Adrian Y. S., Ming-Wei Lin, and Joanne H. Reed. "Anti-Ro52/TRIM21 serological subsets identify differential clinical and laboratory parameters." Clinical Rheumatology, July 23, 2022. http://dx.doi.org/10.1007/s10067-022-06299-5.
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Abstract Introduction Anti-Ro52/tripartite motif-containing protein 21 (TRIM21) IgG is one of the most common autoantibodies found in systemic autoimmune diseases and is typically found in conjunction with anti-Ro60 and/or anti-La. A retrospective, cross-sectional study was undertaken to examine the clinical and laboratory features of two serological subsets: patients with anti-Ro52/TRIM21 autoantibodies in the absence of anti-Ro60 and anti-La (isolated anti-Ro52/TRIM21) and patients with anti-Ro52/TRIM21 in the presence of anti-Ro60 and/or anti-La. Methods Over a 12-month period, patients tested positive for anti-Ro52/TRIM21 via line immunoassay (LIA) at the Westmead Hospital (Australia) immunopathology laboratory were included. The presence of anti-Ro60 and/or anti-La via same LIA was noted. Associated laboratory and medical records were perused to extract demographic, laboratory, and clinical information. Results There were 346 patients within the study period, and 39.9% of the patients positive for anti-Ro52/TRIM21 lacked anti-Ro60/anti-La autoantibodies. Isolated anti-Ro52/TRIM21 patients tend to be older, have lower anti-Ro52/TRIM21 titres, have lower rheumatoid factors, and have lower proportions of neutropaenia compared to patients who were positive for anti-Ro52/TRIM21 and anti-Ro60/La. This occurred independent to diagnoses of Sjögren’s syndrome or systemic lupus erythematosus. Coexisting neurological syndromes, pulmonary pathologies, and malignancies were more prevalent in the isolated anti-Ro52/TRIM21 subset. Conclusions Patients with isolated anti-Ro52/TRIM21 tend to have distinct and important clinical and laboratory associations. It is unclear if these patients evolve or remain a stable subset and how they originate immunologically. Longitudinal and prospective studies are required to ascertain the overall predictive and prognostic value of this stratification. Key Points• Anti-Ro52/TRIM21 is an autoantibody found in autoimmunity and non-immunological conditions.• Sixty percent of anti-Ro52/TRIM21 patients are positive for anti-Ro60.• Isolated anti-Ro52/TRIM21 has reduced anti-Ro52/TRIM21 and rheumatoid factor titres.• Isolated anti-Ro52/TRIM21 is associated with anaemia and malignancies.
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Ringstad, N. K., F. Lingaas, and S. I. Thoresen. "Breed distributions for diabetes mellitus and hypothyroidism in Norwegian dogs." Canine Medicine and Genetics 9, no. 1 (May 24, 2022). http://dx.doi.org/10.1186/s40575-022-00121-w.
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Abstract Background Diabetes mellitus (DM) and hypothyroidism are common canine endocrinopathies. Both canine DM and primary hypothyroidism are assumed to originate from autoimmune destruction of the respective endocrine glands and have been associated with the major histocompatibility complex (MHC) gene region. This study aims to investigate breed distributions for DM and hypothyroidism in the Norwegian canine population by calculating odds ratios (OR) from two different comparator groups. Methods Results from canine serum samples submitted from 2001 to 2018 to the Veterinary Clinical Pathology Laboratory (VCPL) at the Faculty of Veterinary Medicine, Norwegian University of Life Sciences for analysis of fructosamine and thyroid hormones in serum were used as cases in a retrospective bivariate analysis of canine breeds. The ORs were calculated as a measure of risk for the included breeds, where all the submitted blood samples to the VCPL and dogs registered in the Norwegian Kennel Club (NKK), the national organization for dog owners, were used as two comparator groups. Results Significant differences in disease prevalence between breeds were discovered using both comparator groups. Australian terrier, Swedish lapphund, Samoyed, and Schipperke were at highest risk for DM. German Shepherd, Golden retriever, German pointing dog, and Collie presented as the breeds with lowest risk for DM. For hypothyroidism, Schnauzer, Eurasier, Dunker, and English setter were at highest risk for developing the disease. The breeds at lowest risk of developing hypothyroidism were Rottweiler, Dachshund, German shepherd, and Border collie. The results from the different comparator groups gave different ORs and ranks, but the breeds with highest and lowest odds showed the same susceptibility using both comparators. Conclusions These findings support that there are breeds more and less prone to develop DM and hypothyroidism. A strong genetic predisposition involved in the aetiology of these two diseases is therefore likely. Interestingly, there also appeared to be an inverse relationship of odds for the two diseases for some of the breeds since some breeds that had a high OR for DM or hypothyroidism had a lower OR for the other disease. This indicates that there may be different risk alleles/haplotypes for the two diseases. The possible aetiological relationship between canine DM and hypothyroidism should be further investigated.
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Jahnich, Nina, and Peter D. Arkwright. "Regional risk of tuberculosis and viral hepatitis with tumor necrosis factor-alpha inhibitor treatment: A systematic review." Frontiers in Pharmacology 14 (January 20, 2023). http://dx.doi.org/10.3389/fphar.2023.1046306.
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Background: TNFα inhibitors are regularly used to treat autoimmune diseases. Tuberculosis (TB) and viral hepatitis B are considered potential infectious complications, and screening and surveillance are therefore recommended. Current guidelines do not take into account regional differences in endemicity of these infections.Methods: A systematic literature review of TB and viral hepatitis in patients receiving TNFα-inhibitors was performed, searching in PubMed, Embase, MEDLINE and Web of Science databases. Studies were selected against predefined eligibility criteria and assessed using the Newcastle-Ottawa scale. The number of TB and viral hepatitis cases/1,000 TNFα-inhibitor patients were evaluated, and regional variation compared.Results: 105 observational studies involving over 140,000 patients were included. Overall, 1% of patients developed TB or viral hepatitis B. TB cases/1,000 TNFα-inhibitor patients were 4-fold higher in Asia, Africa, and South America than in Europe, North America, and Australasia where only 0%–0.4% of patients developed TB. Hepatitis B cases/1,000 patients were over 15-fold higher in countries with high prevalence (China, Taiwan, South Korea, Thailand) compared with low prevalence (p < 0.00001) where only 0.4% of patients developed hepatitis B. Only three of 143 patients developed viral hepatitis C, and there was insufficient data to allow regional sub-analysis.Conclusion: TB and viral hepatitis B infections in patients treated with TNFα inhibitors are largely confined to countries with high prevalence of these infections. As only 1/2,500 patients in low prevalence countries treated with TNFα inhibitors develop TB or viral hepatitis B, we suggest an individualized, risk-based approach, rather than universal screening for all patients.