Significant joint-destructive association of HLA-DRB1*04:05 independent of DAS28 in rheumatoid arthritis

Tsuji, Hideaki; Ikari, Katsunori; Ohmura, Koichiro; Yano, Koichiro; Furu, Moritoshi; Hashimoto, Motomu; Ito, Hiromu; Fujii, Tomoyuki; Yamamoto, Wataru; Taniguchi, Atsuo; Yamanaka, Hisashi; Mimori, Tsuneyo; Terao, Chikashi

doi:10.1136/annrheumdis-2018-214022

Cited by 3 publications

(2 citation statements)

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“…Since we previously reported that among SE alleles HLA-DRB1*04:05 has unique features in the context of joint destruction20 35 and others reported strong interactive associations between CS and SE alleles (mainly non-*04:05 SE) on ACPA positivity in Europeans,23 27 we assessed whether the associations of SE with autoantibody levels in relation to CS were driven by HLA-DRB1*04:05. However, we did not find a specific association of HLA-DRB1*04:05 (or non-*04:05 SE) (figure 4A,B).…”

Section: Resultsmentioning

confidence: 99%

Shared epitope defines distinct associations of cigarette smoking with levels of anticitrullinated protein antibody and rheumatoid factor

et al. 2019

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ObjectsAlthough the association of cigarette smoking (CS) with susceptibility to rheumatoid arthritis (RA) has been established, the impact of CS on anticitrullinated cyclic peptide/protein antibody (ACPA) and rheumatoid factor (RF) levels in RA has yet been clear, especially in relation to shared epitope (SE) alleles.MethodsA total of 6239 subjects, the largest Asian study ever, from two independent Japanese cohorts were enrolled. Precise smoking histories, levels of ACPA and RF, and HLA-DRB1 allele status were withdrawn from databases. Associations between CS and high ACPA or RF levels, defined by the top quartiles, were evaluated. The effect of HLA-DRB1 alleles on the association was further investigated.ResultsCS at RA onset conferred the risks of high levels of both antibodies, especially RF (OR 2.06, p=7.4×10–14; ACPA, OR 1.29, p=0.012), suggesting that RF level is more sensitive to CS than ACPA level. The patients who had quitted CS before RA onset showed a trend of decreased risks of developing high levels of ACPA or RF, and the risks steadily decreased according to the cessation years. The association of CS with high ACPA level was observed only in subjects carrying SE alleles, while the association of high RF level was observed regardless of SE.ConclusionsCS confers the risks of high autoantibody levels in RA in different manners; CS interacts with SE alleles on ACPA level, while CS impacts on RF level despite SE allele. These data suggest novel distinct production mechanisms of RF and ACPA.

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Section: Resultsmentioning

confidence: 99%

Shared epitope defines distinct associations of cigarette smoking with levels of anticitrullinated protein antibody and rheumatoid factor

et al. 2019

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“…The Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort is an open-label, single-center, observational cohort study of RA and rheumatic diseases [6][7][8]. It was established in 2011, and a total of 4418 patients were registered until 2022.…”

Section: Introductionmentioning

confidence: 99%

Management and treatment outcomes of rheumatoid arthritis in the era of biologic and targeted synthetic therapies: evaluation of 10-year data from the KURAMA cohort

Fujii,

Murata,

Onizawa

et al. 2024

Arthritis Res Ther

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Background Advances in rheumatoid arthritis (RA) treatment, highlighted by biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), have altered the paradigm of RA treatment in the last decade. Therefore, real-world clinical evidence is needed to understand how treatment strategies and outcomes have changed. Methods Using an observational cohort of RA from 2012 to 2021, we collected cross-sectional data of RA patients annually to analyze a trend in RA management. For patients who initiated b/tsDMRDs, we evaluated treatment outcomes between b/tsDMARDs. Mixed-effect models were applied to examine the statistical implications of changes over time in treatment outcomes with a background adjustment. Results We analyzed annual cross-sectional data from 5070 patients and longitudinal data from 1816 patients in whom b/tsDMARDs were initiated between 2012 and 2021. b/tsDMARD use increased, whereas glucocorticoid use decreased from 2012 to 2021. Disease activity and functional disability measures improved over time. The percentage of tsDMARD prescriptions considerably increased. All b/tsDMARDs showed clinical improvements in disease activity and functional disability. Statistically, TNFi showed better short-term improvements in b/tsDMARD-naïve patients, while IL6Ri demonstrated significant long-term benefits. IL6Ri had better retention rates in switched patients. After adjustment for patient characteristics, the annual change of RA disease activity and functional disability fared significantly better from 2012 to 2021. Conclusions With the development of new RA therapeutics, overall treatment outcomes advanced in the past decade.

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Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis

et al. 2022

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Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB1*04:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB1*04:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4+ T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH.

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Significant joint-destructive association of HLA-DRB1*04:05 independent of DAS28 in rheumatoid arthritis

Cited by 3 publications

References 6 publications

Shared epitope defines distinct associations of cigarette smoking with levels of anticitrullinated protein antibody and rheumatoid factor

Shared epitope defines distinct associations of cigarette smoking with levels of anticitrullinated protein antibody and rheumatoid factor

Management and treatment outcomes of rheumatoid arthritis in the era of biologic and targeted synthetic therapies: evaluation of 10-year data from the KURAMA cohort

Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis

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