DataSheet_1_Brief report: Assessment of mucosal barrier integrity using serological biomarkers in preclinical stages of rheumatoid arthritis.xlsx

BackgroundThe pathogenesis of rheumatoid arthritis (RA) is believed to initiate at mucosal sites. The so-called ‘mucosal origin hypothesis of RA’ postulates an increased intestinal permeability before disease onset. Several biomarkers, including lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP), have been proposed to reflect gut mucosa permeability and integrity, while serum calprotectin is a new inflammation marker proposed in RA.
MethodsWe analyzed serum samples of individuals genetically at increased risk of RA in a nested-case-control study. Participants from a longitudinal cohort of first-degree relatives of RA patients (SCREEN-RA cohort) were divided into three pre-clinical stages of RA, based on the presence of risk factors for subsequent RA onset: 1) low-risk healthy asymptomatic controls; 2) intermediate-risk individuals without symptoms, but with RA-associated auto-immunity; 3) high-risk individuals with clinically suspect arthralgias. Five patients with newly diagnosed RA were also sampled. Serum LBP, I-FABP and calprotectin were measured using commercially available ELISA kits.
ResultsWe included 180 individuals genetically at increased risk for RA: 84 asymptomatic controls, 53 individuals with RA-associated autoimmunity and 38 high risk individuals. Serum LBP, I-FAPB or calprotectin concentrations did not differ between individuals in different pre-clinical stages of RA.
ConclusionBased on the serum biomarkers LBP, I-FABP and calprotectin, we could not detect any evidence for intestinal injury in pre-clinical stages of RA.

背景
类风湿关节炎（RA）的发病机制被认为起始于黏膜部位。所谓的“类风湿关节炎黏膜起源假说”提出，在疾病发作前存在肠道通透性升高的情况。已有多项生物标志物被提出用于反映肠道黏膜通透性与完整性，包括脂多糖结合蛋白（LBP）和肠型脂肪酸结合蛋白（I-FABP）；而血清钙卫蛋白（calprotectin）则是一种在类风湿关节炎中被提出的新型炎症标志物。
方法
本研究采用巢式病例对照研究设计，分析了遗传上类风湿关节炎发病风险升高人群的血清样本。研究对象来自类风湿关节炎患者一级亲属的纵向队列（SCREEN-RA队列），依据后续类风湿关节炎发病的危险因素情况，将其分为三个类风湿关节炎临床前阶段：1）低风险健康无症状对照人群；2）无临床症状但存在类风湿关节炎相关自身免疫异常的中风险人群；3）伴有临床可疑关节痛的高风险人群。此外还采集了5名新诊断类风湿关节炎患者的血清样本。采用商品化酶联免疫吸附试验（ELISA）试剂盒检测血清中LBP、I-FAPB及钙卫蛋白的浓度。
结果
本研究共纳入180名遗传上类风湿关节炎发病风险升高的人群：84名无症状对照者、53名存在类风湿关节炎相关自身免疫异常的人群以及38名高风险人群。不同类风湿关节炎临床前阶段人群的血清LBP、I-FAPB及钙卫蛋白浓度均无显著差异。
结论
基于血清生物标志物LBP、I-FABP及钙卫蛋白的检测结果，本研究未在类风湿关节炎临床前阶段发现肠道损伤的相关证据。