Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, United States.
Department of Medicine, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2022 May 25;13:890996. doi: 10.3389/fimmu.2022.890996. eCollection 2022.
BACKGROUND & AIMS: Rheumatoid arthritis (RA) is a prototypic autoimmune disease causing inflammatory polyarthritis that affects nearly 1% of the population. RA can lead to joint destruction and disability along with increased morbidity and mortality. Similar to other autoimmune diseases, RA has distinct preclinical phases corresponding to genetic risk, lifestyle risk factors, autoantibody development, and non-specific symptoms prior to clinical diagnosis. This narrative review will detail observational studies for RA risk and clinical trials for RA prevention as a roadmap to investigating preclinical autoimmunity that could be applied to other diseases.
In this narrative review, we summarized previous and ongoing research studies investigating RA risk and prevention, categorizing them related to their design and preclinical phases.
We detailed the following types of studies investigating RA risk and prevention: retrospective population-based and administrative datasets; prospective studies (case-control and cohort; some enrolling based on genetics, first-degree relative status, elevated biomarkers, or early symptoms/arthritis); and randomized clinical trials. These correspond to all preclinical RA phases (genetic, lifestyle, autoimmunity, early signs/symptoms). Previous and ongoing randomized controlled trials have enrolled individuals at very elevated risk for RA based on biomarkers, symptoms, imaging abnormalities, or early signs/symptoms.
We detailed the rich variety of study designs that is necessary to investigate distinct preclinical phases of an autoimmune disease such as RA. However, further progress is needed to fully elucidate the pathogenesis of RA that may ultimately lead to prevention or delay of disease onset.
类风湿关节炎（RA）是一种典型的自身免疫性疾病，可引起炎症性多关节炎，影响近 1%的人群。RA 可导致关节破坏和残疾，同时增加发病率和死亡率。与其他自身免疫性疾病类似，RA 有明显的临床前阶段，对应于遗传风险、生活方式风险因素、自身抗体的发展以及临床诊断前的非特异性症状。本综述将详细介绍 RA 风险的观察性研究和 RA 预防的临床试验，为研究临床前自身免疫提供路线图，这也可应用于其他疾病。
在本综述中，我们总结了以前和正在进行的研究 RA 风险和预防的研究，根据其设计和临床前阶段进行分类。
我们详细介绍了以下几种研究 RA 风险和预防的方法：回顾性基于人群和行政的数据集；前瞻性研究（病例对照和队列研究；有些研究基于遗传、一级亲属状况、升高的生物标志物或早期症状/关节炎进行招募）；和随机临床试验。这些方法对应于 RA 的所有临床前阶段（遗传、生活方式、自身免疫、早期症状/体征）。以前和正在进行的随机对照试验已经根据生物标志物、症状、影像学异常或早期症状/体征招募了处于极高 RA 风险的个体。
我们详细介绍了研究 RA 等自身免疫性疾病不同临床前阶段所需的各种研究设计。然而，需要进一步的进展来充分阐明 RA 的发病机制，这可能最终导致疾病的预防或发病延迟。
