Racial variability in immune responses only partially explains differential systemic sclerosis disease severity.

IF 20.3 1区 医学 Q1 RHEUMATOLOGY Annals of the Rheumatic Diseases Pub Date : 2024-10-21 DOI:10.1136/ard-2023-225458
Kamini E Kuchinad, Ji Soo Kim, Adrianne Woods, Gwen Leatherman, Laura Gutierrez-Alamillo, Maureen D Mayes, Robyn Domsic, Paula S Ramos, Richard M Silver, John Varga, Lesley Ann Saketkoo, Suzanne Kafaja, Victoria K Shanmugan, Jessica Gordon, Lorinda Chung, Elana J Bernstein, Pravitt Gourh, Francesco Boin, Daniel L Kastner, Scott L Zeger, Livia Casciola-Rosen, Fredrick M Wigley, Ami A Shah
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Abstract

Objective: To understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients.

Methods: 803 black and 2178 white SSc patients had systematic testing for autoantibodies using Euroimmun (centromere (ACA), RNA-polymerase III (POLR3), Scl70, PM/Scl, NOR90, Th/To, Ku, U3RNP and Ro52) and commercial ELISA (U1RNP). In this observational study, logistic regression was performed to assess the association between self-identified race and outcomes, adjusting for autoantibodies. To estimate whether the effect of race was mediated by autoantibody status, race coefficients from multivariate models including and excluding autoantibodies were compared.

Results: Anti-Scl70, anti-U1RNP, anti-U3RNP, anti-Th/To, anti-Ku and anti-NOR90 were more common in the black cohort than in the white cohort, which was enriched for ACA, anti-POLR3 and anti-PM/Scl. Black individuals had a higher prevalence of severe Raynaud's, skin, lung, gastrointestinal and renal disease whereas white individuals had a higher prevalence of severe heart and muscle disease. Adjusting for autoantibodies decreased the effect of race on outcome for telangiectasias, forced vital capacity <70%, pulmonary hypertension and severe lung, heart, muscle and gastrointestinal disease by 11%-44% and increased the association between race and renal crisis and severe kidney disease by 37%-52%.

Conclusions: This study is the largest systematic analysis of autoantibody responses in a geographically diverse population of black SSc patients. Black and white individuals with SSc have distinct autoantibody profiles. Autoantibodies explain only a fraction of the effect of race on clinical outcomes, suggesting other factors contribute to disparate outcomes between these groups.

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免疫反应的种族差异只能部分解释系统性硬化症疾病严重程度的不同。
目的方法:803 名黑人和 2178 名白人 SSc 患者使用 Euroimmun(中心粒 (ACA)、RNA 聚合酶 III (POLR3)、Scl70、PM/Scl、NOR90、Th/To、Ku、U3RNP 和 Ro52)和商用 ELISA(U1RNP)系统检测了自身抗体。在这项观察性研究中,对自身抗体进行调整后,采用逻辑回归法评估自我认定的种族与结果之间的关系。为了估计种族的影响是否由自身抗体状态介导,比较了包括和不包括自身抗体的多变量模型中的种族系数:黑人队列中抗Scl70、抗U1RNP、抗U3RNP、抗Th/To、抗Ku和抗NOR90比白人队列中更常见,而白人队列中则富含ACA、抗POLR3和抗PM/Scl。对自身抗体进行调整后,种族对毛细血管扩张症、强迫生命体征能力结果的影响有所降低:这项研究是对不同地域的黑人 SSc 患者自身抗体反应进行的最大规模的系统分析。黑人和白人 SSc 患者的自身抗体情况截然不同。自身抗体只能解释种族对临床结果影响的一小部分,这表明其他因素导致了这些群体之间的结果差异。
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来源期刊
Annals of the Rheumatic Diseases
Annals of the Rheumatic Diseases 医学-风湿病学
CiteScore
35.00
自引率
9.90%
发文量
3728
审稿时长
1.4 months
期刊介绍: Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
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