Table_3_Coordinated Induction of Antimicrobial Response Factors in Systemic Lupus Erythematosus.XLSX

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by dysregulated autoantibody production and complement activation leading to multi-organ damage. The disease is associated with increased intestinal permeability. In this study, we tested the hypothesis that SLE subjects have increased systemic exposure to bacteria. Since bacteria induce the expression of antimicrobial response factors (ARFs), we measured the levels of a series of clinically relevant ARFs in the plasma of SLE subjects. We found that levels of sCD14, lysozyme, and CXCL16 were significantly elevated in SLE subjects. A strong positive correlation was also observed between sCD14 and SELENA-SLEDAI score. Interestingly, the ratio of EndoCAb IgM:total IgM was significantly decreased in SLE and this ratio was negatively correlated with sCD14 levels. Although, there were no significant differences in the levels of lipopolysaccharide binding protein (LBP) and fatty acid binding protein 2 (FABP2), we observed significant positive correlations between lysozyme levels and sCD14, LBP, and FABP2. Moreover, galectin-3 levels also positively correlate with lysozyme, sCD14, and LBP. Since our SLE cohort comprised 43.33% males, we were able to identify gender-specific changes in the levels of ARFs. Overall, these changes in the levels and relationships between ARFs link microbial exposure and SLE. Approaches to reduce microbial exposure or to improve barrier function may provide therapeutic strategies for SLE patients.

系统性红斑狼疮（SLE）是一种以自身抗体产生失调和补体激活为特征，导致多器官损伤的慢性自身免疫性疾病。该疾病与肠道通透性增加相关。在本研究中，我们检验了系统性红斑狼疮患者细菌系统性暴露增加的假设。由于细菌诱导抗菌反应因子（ARFs）的表达，我们测量了系统性红斑狼疮患者血浆中一系列临床相关ARFs的水平。我们发现sCD14、溶菌酶和CXCL16的水平在系统性红斑狼疮患者中显著升高。sCD14与SELENA-SLEDAI评分之间也存在强烈的正相关关系。有趣的是，EndoCAb IgM与总IgM的比值在系统性红斑狼疮患者中显著降低，且此比值与sCD14水平呈负相关。尽管脂多糖结合蛋白（LBP）和脂肪酸结合蛋白2（FABP2）的水平没有显著差异，但我们观察到溶菌酶水平与sCD14、LBP和FABP2之间存在显著的阳性相关性。此外，半乳糖凝集素-3水平也与溶菌酶、sCD14和LBP呈正相关。由于我们的系统性红斑狼疮队列中男性占43.33%，我们能够识别出ARFs水平中的性别特异性变化。总体而言，这些ARFs水平和相互关系的变化将微生物暴露与系统性红斑狼疮联系起来。降低微生物暴露或改善屏障功能的策略可能为系统性红斑狼疮患者的治疗方案提供思路。