Background

Networks formed of numerous autoantibodies (aabs) directed against G-protein coupled receptors (GPCR) have been suggested to play important role in autoimmune disorders. In present study, we aimed to evaluate the association between anti-GPCR antibodies and primary Sjogren’s syndrome (pSS) to determine the potential pathogenic factors.

Methods

By applying a cell membrane-based ELISA technique, which is capable of detecting aabs against conformational epitopes within GPCR, serum levels of fourteen GPCR were determined in well-characterized patients with pSS (n = 52) and gender-matched healthy controls (n = 54). Comparisons between groups were analyzed by two-tailed Mann-Whitney U test, Bonferroni correction was applied for multiple comparisons. Spearman`s rank correlation coefficients were calculated between variables and visualized by heat map.

Results

Compared to healthy subjects, sera of patients with pSS showed significantly higher binding to β2AR and ETAR, but lower binding to C5aR1, C3aR1, CXCR3, and CXCR4. Autoantibodies against C5aR1, C3aR1, CXCR3, and CXCR4 were also decreased in patients with rheumatoid arthritis. In pSS patients, levels of anti-CXCR3 and anti-CXCR4 antibodies were negatively correlated with circulating lymphocyte counts. Furthermore, correlation signatures of anti-GPCR antibodies changed dramatically in the patients with pulmonary involvement.

Conclusions

This study demonstrates an association between pSS and autoantibodies recognizing GPCR, especially those functionally involved in immune cell migration and exocrine glandular secretion.

中文翻译：

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在原发性干燥综合征中，针对C5aR1，C3aR1，CXCR3和CXCR4的自身抗体减少

背景

已提出由针对G蛋白偶联受体（GPCR）的众多自身抗体（aabs）形成的网络在自身免疫性疾病中起重要作用。在本研究中，我们旨在评估抗GPCR抗体与原发性干燥综合征（pSS）之间的关联，以确定潜在的致病因素。

方法

通过使用基于细胞膜的ELISA技术，该技术能够检测GPCR内构象表位的aab，在特征明确的pSS患者（n = 52）和性别匹配的健康对照（n = 54）。组间比较通过两尾Mann-Whitney U检验进行分析，Bonferroni校正用于多次比较。计算变量之间的Spearman秩相关系数，并通过热图可视化。

结果

与健康受试者相比，pSS患者的血清显示出与β2AR和ETAR的结合明显更高，但与C5aR1，C3aR1，CXCR3和CXCR4的结合却更低。类风湿关节炎患者的针对C5aR1，C3aR1，CXCR3和CXCR4的自身抗体也降低了。在pSS患者中，抗CXCR3和抗CXCR4抗体的水平与循环淋巴细胞计数呈负相关。此外，在肺部受累患者中，抗GPCR抗体的相关特征发生了巨大变化。

结论

这项研究证明了pSS和识别GPCR的自身抗体之间的关联，尤其是功能上参与免疫细胞迁移和外分泌腺分泌的抗体。