Language：English   Publishing type：Research paper (scientific journal)  

Idiopathic inflammatory myopathies (IIM), or myositis, are a heterogeneous group of systemic autoimmune disorders that are associated with significant morbidity and mortality. Conducting high-quality clinical trials in IIM is challenging due to the rare and variable presentations of disease. To address this challenge, the Myositis Clinical Trials Consortium (MCTC) was formed. MCTC is a collaborative international alliance dedicated to facilitating, promoting, coordinating and conducting clinical trials and related research in IIM. This partnership works to advance the discovery of effective evidence-based treatments for IIM by integrating a diverse group of clinical investigators, research professionals, medical centres, patient groups, and industry partners. The Steering Committee, Core Group, and Paediatric Subcommittee of MCTC are comprised of myositis experts and junior investigators from around the world, representing a diversity of genders, geographies, and subspecialties. MCTC works alongside other current myositis organisations to complement existing work by concentrating on the operationalisation of clinical trials. Our pilot Myositis Investigators' Information Survey gathered responses from 173 myositis investigators globally and found considerable variability in proficiency with outcome measures, geographic disparities in patient recruitment, and a significant disconnect between investigators' routine myositis patient load and clinical trial enrolment. MCTC will meet the need to support and diversify myositis clinical trials by facilitating trial planning, feasibility assessments, site selection, and the training and mentoring of junior investigators/centres to establish their readiness for clinical trial participation. Through experienced leadership, strategic collaborations, and interdisciplinary discussions, MCTC will establish standards for IIM clinical trial design, protocols, and outcome measures in myositis.

DOI： 10.55563/clinexprheumatol/k7665a

PubMed

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Clinical and Experimental Rheumatology  

DOI： 10.55563/clinexprheumatol/9s7djz

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Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1756-185X.70101

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Objective

Anti‐synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data‐driven classification criteria for ASSD.

Methods

We utilized a large, international, multi‐center “Classification Criteria for Anti‐synthetase Syndrome” (CLASS) project database, which includes both ASSD patients and controls with mimicking conditions, namely SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort.

Results

Our analysis included 948 ASSD cases and 1077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo‐1 and non‐Jo‐1 anti‐synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti‐Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/MRI/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between ASSD and controls or were inversely associated with ASSD.

Conclusion

We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data‐driven classification criteria for ASSD.

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DOI： 10.1002/art.43038

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/rap/rkae098

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/mr/road094

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/rap/rkae049

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Clinical and Experimental Rheumatology  

DOI： 10.55563/clinexprheumatol/s14zq8

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Objectives

To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and without autoimmune diseases (controls), using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database.

Methods

Demographics, diagnosis, comorbidities, disease activity, treatments, and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis.

Results

We analysed responses from 1582 IIMs, 4700 non-IIM AIRDs, 545 nrAIDs, and 3675 controls gathered until May 23, 2022. GPH median (IQR) scores were the lowest in IIMs and non-IIM AIRDs (13 [10–15] IIMs vs.s 13 [11–15] non-IIM AIRDs vs.s 15 [13–17] nrAIDs vs.s 17 [15–18] controls, p < 0.001). GMH median (IQR) scores in IIMs were also significantly lower compared with those without autoimmune diseases (13 [10–15] IIMs vs.s 15 [13–17] controls, p < 0.001). Inclusion body myositis, comorbidities, active disease, and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function-10a, and higher PROMIS Fatigue-4a scores were associated with lower GMH scores in IIMs.

Conclusion

Both physical and mental health are significantly impaired in IIMs, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

DOI： 10.1093/rap/rkae028

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Interferon-lambda 3 (IFN-λ3) is a cytokine with antiviral functions on barrier surfaces, and it is associated with disease activity in autoimmune diseases. This study assessed the clinical significance of serum IFN-λ3 levels in polymyositis (PM)/dermatomyositis (DM)-associated interstitial lung disease (ILD). METHODS: We measured serum IFN-λ3 levels in 221 patients with PM/DM-ILD (155 in the derivation cohort, 66 in the validation cohort) and 38 controls. We evaluated factors associated with mortality risk among 79 patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM-ILD. RESULTS: Serum IFN-λ3 levels at diagnosis were significantly higher in patients with PM/DM-ILD than in healthy controls. Remarkably, serum IFN-λ3 levels were specifically increased in patients with anti-MDA5 antibody-positive DM-ILD in both the derivation and validation cohorts. In anti-MDA5 antibody-positive DM-ILD, patients with high IFN-λ3 levels (>120 pg/mL) had significantly lower survival rates than those with low IFN-λ3 levels (≤120 pg/mL). Multivariate analysis revealed that high IFN-λ3 levels, as well as old age and low PaO2 , were significantly associated with poor prognoses in patients with anti-MDA5 antibody-positive DM-ILD. In a classification analysis of patients with anti-MDA5 antibody-positive DM-ILD based on age, IFN-λ3, and PaO2 , patients with old age (>53 years), high IFN-λ3 levels (>120 pg/mL), and low PaO2 (<75 Torr) had the worst survival. In lung pathological analyses, IFN-λ3-positive staining was observed in macrophages, airway epithelial cells, the pleural region and intrapulmonary veins in anti-MDA5 antibody-positive DM-ILD. CONCLUSION: Serum IFN-λ3 is a promising biomarker for identifying patients at high risk of poor outcomes in anti-MDA5 antibody-positive DM-ILD. This article is protected by copyright. All rights reserved.

DOI： 10.1002/art.42785

PubMed

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/diagnostics13243621

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Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11926-023-01120-x

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/S00296-023-05441-Z

Web of Science

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Language：English   Publishing type：Research paper (scientific journal)  

Objective Drug fever is defined as a fever that temporally coincides with the start of a culprit drug and disappears after discontinuation of the drug. It is a common cause of nosocomial fever, which refers to a fever that develops beyond the first 48 h after hospital admission. However, the exact prevalence of drug fever among cases of nosocomial fever is unclear, as is the variation in prevalence depending on the clinical setting and most common causative drugs. Methods PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials. gov were systematically searched. Studies that reported the prevalence of drug fever in patients with nosocomial fever were included. Two of the four reviewers conducted independent assessments of the inclusion, data extraction, and quality. Pooled adjusted odds ratios were generated using a random-effects model and presented with 95% confidence intervals (CIs). Results Fifteen meta-analysis from 15 studies were included. Ten studies did not report the definition of drug fever or excluded febrile patients who were admitted to the hospital within 24-48 h. The pooled prevalence of drug fever among cases of nosocomial fever was 3.0% (95% CI, 0.6%-6.8%), which was largely consistent across the settings, except for at Oriental Medicine Hospital. Only four studies reported the causative agents, and antibiotics were the most frequently reported. Conclusions The prevalence of drug fever is low in patients with nosocomial fever. Clinicians should recognize that drug fever is a diagnosis of exclusion, even in cases of nosocomial fever.

DOI： 10.2169/internalmedicine.2322-23

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/rheumatology/keac603

Web of Science

Scopus

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Objectives

The assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs.

Methods

Demographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease.

Results

A total of 1057 IIM patients, 3635 non-IIM AIRD patients and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs [36.3 (95% CI 35.5, 37.1) vs 41.3 (95% CI 40.2, 42.5) vs 46.2 (95% CI 45.8, 46.6), P &amp;lt; 0.001], irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis.

Conclusion

Physical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs.

DOI： 10.1093/rheumatology/keac441

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Other Link： https://academic.oup.com/rheumatology/article-pdf/62/3/1204/49356050/keac441.pdf

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

Objective:

Severe digital ischemia, including digital ulcers and gangrene, is considered rare in patients with antisynthetase antibodies. This study aimed to elucidate the clinical features of antisynthetase-positive patients complicated with digital ulcers and/or gangrene using a systematic literature review and case series in a single-center cohort.

Methods:

A systematic literature review was conducted to identify reports describing antisynthetase-positive cases with digital ulcers and/or gangrene. Our cohort of consecutive patients with antisynthetase antibodies was stratified by the history of severe digital ischemia. Demographic and clinical features and outcomes in patients with severe digital ischemia identified in the systematic literature review and our cohort were compared with those in patients without severe digital ischemia in our cohort.

Results:

The systematic literature review revealed 12 antisynthetase-positive patients with severe digital ischemia from one case series and eight case reports. Seven (7%) of 100 patients with antisynthetase antibodies in our cohort had a record of severe digital ischemia. Severe digital ischemia was often found at presentation and was associated with the classification of systemic sclerosis with or without myositis overlap. Clinical features associated with severe digital ischemia in antisynthetase-positive patients included Raynaud’s phenomenon ( p &lt; 0.001), digital pitting scars ( p = 0.001), and nailfold capillary abnormality ( p = 0.02). Outcomes of severe digital ischemia were generally favorable with vasodilators.

Conclusion:

Severe digital ischemia is an overlooked complication in antisynthetase-positive patients. Antisynthetase antibodies should be measured in patients presenting with digital ulcers or gangrene, especially in those with systemic sclerosis phenotype and features associated with antisynthetase antibodies in the absence of systemic sclerosis-specific autoantibodies.

DOI： 10.1177/23971983221090857

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/23971983221090857

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/acr2.11423

Scopus

PubMed

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/acr2.11423

Language：English   Publishing type：Research paper (scientific journal)  

Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat-shock protein 70 (HSP-70) and heme oxygenase 1 (HO-1) and promoted cell survival after hypothermia-hypoxia insult in human proximal tubular (HK-2) cells, which was abolished by HSP-70 or HO-1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T-cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.

DOI： 10.1096/fj.13-232173

PubMed

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Authorship：Lead author   Language：Japanese   Publisher：(一社)日本リウマチ学会  

J-GLOBAL

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Authorship：Lead author   Publishing type：Research paper, summary (international conference)  

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Publishing type：Research paper, summary (international conference)   Publisher：BMJ Publishing Group Ltd and European League Against Rheumatism  

DOI： 10.1136/annrheumdis-2024-eular.1667

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Publishing type：Research paper, summary (international conference)   Publisher：BMJ Publishing Group Ltd and European League Against Rheumatism  

DOI： 10.1136/annrheumdis-2024-eular.3269

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Authorship：Lead author   Publishing type：Research paper, summary (international conference)   Publisher：BMJ Publishing Group Ltd and European League Against Rheumatism  

DOI： 10.1136/annrheumdis-2024-eular.3674

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Authorship：Lead author   Language：English   Publisher：BMJ Publishing Group Ltd and European League Against Rheumatism  

OBJECTIVE: Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD. METHODS: We utilized a large, international, multi-center "Classification Criteria for Anti-synthetase Syndrome" (CLASS) project database, which includes both ASSD patients and controls with mimicking conditions, namely SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort. RESULTS: Our analysis included 948 ASSD cases and 1077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo-1 and non-Jo-1 anti-synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti-Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/MRI/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between ASSD and controls or were inversely associated with ASSD. CONCLUSION: We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data-driven classification criteria for ASSD.

DOI： 10.1136/annrheumdis-2024-eular.2277

PubMed

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Authorship：Lead author   Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Authorship：Lead author  

J-GLOBAL

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Authorship：Lead author   Publishing type：Research paper, summary (international conference)   Publisher：BMJ Publishing Group Ltd and European League Against Rheumatism  

DOI： 10.1136/annrheumdis-2023-eular.4418

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Language：Japanese   Publisher：関東リウマチ研究会  

症例は10歳男児で、多関節痛、筋力低下、紅斑を主訴とした。入院時身体所見、皮膚所見、血液検査、画像所見より抗MDA5抗体陽性若年性皮膚筋炎と診断した。主体は皮膚・筋・関節病変で、間質性肺炎は軽微であった。メチルプレドニゾロン(mPSL)投与後、PSL、シクロフォスファミド間欠静注療法を行った。治療開始2週間後に関節症状の速やかな改善・CDASI低下・CMAS上昇、3ヵ月後に左上葉すりガラス影の消失を認めた。

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Authorship：Lead author   Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Authorship：Lead author   Publishing type：Research paper, summary (international conference)   Publisher：Elsevier BV  

DOI： 10.1016/s2665-9913(22)00289-2

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Authorship：Lead author   Publishing type：Research paper, summary (international conference)   Publisher：BMJ  

Background

Evaluation of physical function is fundamental in the management of idiopathic inflammatory myopathies (IIMs). Patient-Reported Outcome Measurement Information System (PROMIS) is a National Institute of Health initiative established in 2004 to develop patient-reported outcome measures (PROMs) with improved validity and efficacy. PROMIS Physical Function (PF) short forms have been validated for use in IIMs [1].

Objectives

To investigate the physical function status of IIM patients compared to those with non-IIM autoimmune diseases (AIDs) and healthy controls (HCs) utilizing PROMIS PF data obtained in the coronavirus disease-2019 (COVID-19) Vaccination in Autoimmune Diseases (COVAD) study, a large-scale, international self-reported e-survey assessing the safety of COVID-19 vaccines in AID patients [2].

Methods

The survey data regarding demographics, IIM and AID diagnosis, disease activity, and PROMIS PF short form-10a scores were extracted from the COVAD study database. The disease activity (active vs inactive) of each patient was assessed in 3 different ways: (1) physician’s assessment (active if there was an increased immunosuppression), (2) patient’s assessment (active vs inactive as per patient), and (3) current steroid use. These 3 definitions of disease activity were applied independently to each patient. PROMIS PF-10a scores were compared between each disease category (IIMs vs non-IIM AIDs vs HCs), stratified by disease activity based on the 3 definitions stated above, employing negative binominal regression model. Multivariable regression analysis adjusted for age, gender, and ethnicity was performed clustering countries, and the predicted PROMIS PF-10a score was calculated based on the regression result. Factors affecting PROMIS PF-10a scores other than disease activity were identified by another multivariable regression analysis in the patients with inactive disease (IIMs or non-IIM AIDs).

Results

1057 IIM patients, 3635 non-IIM AID patients, and 3981 HCs responded to the COVAD survey until August 2021. The median age of the respondents was 43 [IQR 30-56] years old, and 74.8% were female. Among IIM patients, dermatomyositis was the most prevalent diagnosis (34.8%), followed by inclusion body myositis (IBM) (23.6%), polymyositis (PM) (16.2%), anti-synthetase syndrome (11.8%), overlap myositis (7.9%), and immune-mediated necrotizing myopathy (IMNM) (4.6%). The predicted mean of PROMIS PF-10a scores was significantly lower in IIMs compared to non-IIM AIDs or HCs (36.3 [95% (CI) 35.5-37.1] vs 41.3 [95% CI 40.2-42.5] vs 46.2 [95% CI 45.8-46.6], P &lt; 0.001), irrespective of disease activity or the definitions of disease activity used (physician’s assessment, patient’s assessment, or steroid use) (Figure 1). The largest difference between active IIMs and non-IIM AIDs was observed when the disease activity was defined by patient’s assessment (35.0 [95% CI 34.1-35.9] vs 40.1 [95% CI 38.7-41.5]). Considering the subgroups of IIMs, the scores were significantly lower in IBM in comparison with non-IBM IIMs (P &lt; 0.001). The independent factors associated with low PROMIS PF-10a scores in the patients with inactive disease were older age, female gender, and the disease category being IBM, PM, or IMNM.

Conclusion

Physical function is significantly impaired in IIMs compared to non-IIM AIDs or HCs, even in patients with inactive disease. The elderly, women, and IBM groups are the worst affected, suggesting that developing targeted strategies to minimize functional disability in certain groups may improve patient reported physical function and disease outcomes.

References

[1]Saygin D, Oddis CV, Dzanko S, et al. Utility of patient-reported outcomes measurement information system (PROMIS) physical function form in inflammatory myopathy. Semin Arthritis Rheum. 2021; 51: 539-46.

[2]Sen P, Gupta L, Lilleker JB, et al. COVID-19 vaccination in autoimmune disease (COVAD) survey protocol. Rheumatol Int. 2022; 42: 23-9.

Acknowledgements

The authors thank all respondents for filling the questionnaire. The authors thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren’s India Foundation, EULAR PARE, and various other patient support groups and organizations for their invaluable contribution in the dissemination of this survey among patients which made the data collection possible. The authors also thank all members of the COVAD study group.

Disclosure of Interests

None declared

DOI： 10.1136/annrheumdis-2022-eular.1045

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Language：Japanese   Publisher：日本救急医学会-関東地方会  

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Language：Japanese   Publisher：関東リウマチ研究会  

症例は前医にてリウマチ性多発筋痛症(PMR)としてプレドニゾロン(PSL)で加療していた83歳女性で、後頸部痛を主訴とした。精査にて右手関節の軽度の滑膜肥厚、右尺頭骨の骨糜爛、PF陰性、抗CCP陰性を認め、関節リウマチ(RA)と診断した。また、環軸関節の骨膜炎、歯突起周囲のパンヌス形成、椎体終板の骨糜爛、骨髄浮腫を認めたことより、RAの頸椎病変を原因とする頸部痛と考え、メトトレキサート(MTX)を投与した。退院後は外来にてMTX、ゴリムマブを投与した結果、検査値、画像所見、頸部痛、頸部可動域は改善を得た。

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本救急医学会  

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Authorship：Lead author   Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Authorship：Lead author   Publishing type：Research paper, summary (international conference)   Publisher：BMJ  

Background:

Anti-Ro/SS-A (anti-SS-A) antibody is one of myositis-associated antibodies, and is found in patients with anti-synthetase antibodies¹. Anti-SS-A antibody targets the complex consisting of Ro52 and Ro60 proteins coupled with cytoplasmic non-coding Y-RNAs. Autoantibody against Ro52 uncoupled with Y-RNAs (anti-uncoupled Ro52) is also present in patients with a variety of connective tissue diseases, including myositis². However, the majority of previous studies used enzyme-linked immunoassay (EIA) for detection of anti-Ro52 antibodies, resulting in failure to discriminate between anti-Ro52 antibodies coupled and uncoupled with Y-RNAs. The prevalence and clinical significance of anti-uncoupled Ro52 antibodies still remain unclear in patients with anti-synthetase antibodies.

Objectives:

To elucidate clinical relevance of anti-uncoupled Ro52 antibodies in a cohort of anti-synthetase syndrome employing RNA immunoprecipitation assay (RNA-IP) in combination with EIA.

Methods:

This is a single-center, cross-sectional study involving 80 patients positive for anti-synthetase antibodies by RNA-IPP. Complete clinical information was obtained from a medical chart review. Serum samples were obtained at first visit and stored at -20°C until use. Anti-SS-A and anti-SS-B antibodies were detected by RNA-IP, and anti-Ro52 and anti-Ro60 antibodies were measured by commercial EIA kits (ORGENTIC, Mainz, Germany). Autoantibodies that immunoprecipitated Y-RNAs regardless of results of anti-anti-Ro52 or anti-Ro60 EIAs were regarded as anti-SS-A antibody, while antibodies that did not immunoprecipitate Y-RNAs but reacted with anti-Ro52 antibodies by EIA were regarded as anti-uncoupled Ro52 antibody. Student’s t-test, Mann-Whitney’s U test, and Fisher’s exact test were employed to compare the clinical features between each group. Cumulative survival rates were compared using log-rank test.

Results:

In our cohort of 80 patients with anti-synthetase antibody, mean age at diagnosis was 61 ± 12 years, and 76% were female. Clinical diagnosis was classic dermatomyositis (cDM) in 11, clinically amyopathic dermatomyositis (CADM) in 21, polymyositis (PM) in 11, systemic sclerosis (SSc) in 3, myositis-SSc overlap in 5, interstitial lung disease (ILD) alone in 29, and unclassified in 3. The antigenic specificity of anti-synthetase antibodies included Jo-1 in 19, PL-7 in 12, PL-12 in 9, EJ in 21, OJ in 4, and KS in 16. Anti-SS-A anti-SS-B antibodies were found in 14 (17%) and 2 (2.5%) patients, respectively. The presence of anti-Ro60 and anti-SS-A antibodies was almost concordant (P &lt; 0.0001), although the presence of anti-Ro52 and anti-SS-A antibodies was not correlated (P = 0.8). This was primarily because of high prevalence (40%) of autoantibodies to uncoupled Ro52. Interestingly, prevalence of anti-uncoupled Ro52 antibodies was different among antigenic specificities of anti-synthetase antibodies: high in Jo-1 (58%) and EJ (55%), and low in PL-7 (8%) and OJ (0%). Gottron’s sign/papule was more frequent in patients with anti-uncoupled Ro52 than in those without (61% versus 28%, P = 0.005), resulting in clinical diagnosis of cDM or CADM more common in patients with anti-uncoupled Ro52 than in those without (59% versus 26%; P = 0.003). The prevalence and extent of ILD tended to be greater in anti-uncoupled Ro52-positive versus negative patients, but difference did not reach statistical significance. There were no differences in cumulative survival rates between patients stratified by the presence or absence of anti-uncoupled Ro52 antibodies.

Conclusion:

Autoantibodies to uncoupled Ro52 were commonly found in patients with anti-synthetase antibodies. Anti-Ro52 positivity might be useful for subclassifying anti-synthetase syndrome.

References:

[1]McHugh NJ et al.Nat Rev Rheumatol. 2018;14(5): 290-302.

[2]Schulte-Pelkum J et al.Autoimmun Rev. 2009;8(7): 632-7.

Disclosure of Interests:

Akira Yoshida: None declared, Yuka Okazaki: None declared, Takahisa Gono Speakers bureau: Astellas, and Medical and Biological Laboratories, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim)

DOI： 10.1136/annrheumdis-2020-eular.3993

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Authorship：Lead author   Language：Japanese   Publisher：日本リウマチ学会-関東支部  

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Language：Japanese   Publisher：日本リウマチ学会-関東支部  

researchmap