Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis
Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis
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DOI：
10.3389/fimmu.2020.00427
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发表时间：
2020-03-20
影响因子：
7.3
通讯作者：
Sarvetnick, Nora E.
中科院分区：
文献类型：
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作者：
Ayyappan, Prathapan;Harms, Robert Z.;Sarvetnick, Nora E.
类风湿性关节炎（RA）是一种慢性进行性自身免疫性疾病，随着时间的推移会导致相当大的残疾。这种疾病的特征是血清和滑液中存在多种自身抗体。微生物生态失调被认为在RA的发病机制中起作用。增加全身细菌暴露导致循环中抗菌反应因子（ARFs）水平升高。在本研究中，我们通过分析RA患者和健康年龄和性别匹配的对照组血清中多种ARFs的水平来检测RA患者是否有ARFs水平升高。与健康对照相比，RA患者的可溶性CD14 （sCD14）、溶菌酶和CXCL16水平显著升高。与健康对照相比，RA患者的脂多糖结合蛋白（LBP）水平保持不变。在类风湿因子（RF）中也发现腰痛与类风湿因子（RF）呈正相关。有趣的是，与健康对照组相比，RA患者的抗内毒素核心抗体（EndoCAb） IgM、总IgM、EndoCAb IgA和总IgA水平显著升高。与健康对照组相比，RA患者的EndoCAb IgG和总IgG水平没有明显变化。此外，溶菌酶和CXCL16水平与RA患者疾病严重程度呈正相关。几种arf水平的增加及其与临床指标的相关性表明RA队列中存在系统性微生物暴露。微生物暴露的调节可能在RA患者的疾病发病机制中起重要作用。
Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. Increased systemic bacterial exposure leads to elevated levels of antimicrobial response factors (ARFs) in the circulation. In the present study, we tested whether RA patients have increased levels of ARFs by analyzing the levels of multiple ARFs in serum from RA patients and healthy age and sex-matched controls. The levels of soluble CD14 (sCD14), lysozyme, and CXCL16 were significantly elevated in RA patients compared to healthy controls. Lipopolysaccharide binding protein (LBP) levels remained unchanged in RA patients compared to healthy controls. A positive correlation of LBP with rheumatoid factor (RF) was also found in RA subjects. Interestingly, the levels of anti-endotoxin core antibodies (EndoCAb) IgM, total IgM, EndoCAb IgA, and total IgA were significantly elevated in RA patients compared to healthy controls. No significant changes in the levels of EndoCAb IgG and total IgG were observed in RA patients compared to healthy controls. Furthermore, lysozyme and CXCL16 levels were positively correlated with disease severity among RA subjects. Increases in the levels of several ARFs and their correlations with clinical indices suggest systemic microbial exposure in the RA cohort. Modulation of microbial exposure may play an important role in disease pathogenesis in individuals with RA.