Table_3_Elevated CCL19/CCR7 Expression During the Disease Process of Primary Sjögren's Syndrome.DOCX

Primary Sjögren's syndrome (pSS) is a common chronic autoimmune disease characterized by a high prevalence of autoantibodies and lymphocyte-mediated exocrine gland damage. To enhance our understanding of the mechanisms underlying the progression of the disease and to discover potential biomarkers for the early diagnosis of pSS, we applied RNA sequencing to compare the gene expression patterns in minor salivary glands between pSS patients and non-pSS. A total of 293 differentially expressed genes (DEGs) were detected in pSS vs. non-pSS (FDR < 0.05, fold changes > 2). Of these DEGs, 285 (97.26%) were up-regulated, with most being involved in immune system activation, especially in the formation of the immunological synapse. Significantly elevated CCL19/CCR7 expression in the salivary gland was found to be related to anti-Sjögren's syndrome-related antigen A (SSA) antibody and IgG levels in pSS patients, which was further confirmed in a larger cohort. Up-regulated gene expression showed strong discriminatory accuracy in identifying pSS with area under the curve of 0.98 using receiver operating characteristic curve analysis. In conclusion, gene expression changes in pSS include strong markers of immunological activation and have good discriminatory power in identifying patients with pSS.

原发性干燥综合征（Primary Sjögren's syndrome, pSS）是一种常见的慢性自身免疫性疾病，以自身抗体高阳性率及淋巴细胞介导的外分泌腺损伤为主要特征。为加深我们对该疾病进展相关分子机制的认识，并发掘pSS早期诊断的潜在生物标志物，本研究通过RNA测序（RNA sequencing）技术对比了pSS患者与非pSS对照人群小唾液腺的基因表达谱。在pSS组与非pSS对照组间共检测到293个差异表达基因（differentially expressed genes, DEGs）（错误发现率（FDR）<0.05，差异倍数>2）。其中285个（97.26%）为上调基因，绝大多数参与免疫系统激活过程，尤其与免疫突触的形成密切相关。研究发现，pSS患者唾液腺中CCL19/CCR7的表达水平显著升高，且与患者体内抗干燥综合征相关抗原A（SSA）抗体及免疫球蛋白G（IgG）水平呈相关性，该结论在更大规模的临床队列中得到了进一步验证。经受试者工作特征曲线（receiver operating characteristic curve, ROC）分析，上调基因的表达特征对pSS具有优异的鉴别效能，其曲线下面积（area under the curve, AUC）达0.98。综上，pSS患者的基因表达改变包含显著的免疫激活相关标志物，且具备良好的pSS患者鉴别能力。