Rheumatology Department, First Affiliated Hospital of Wenzhou Medical University, Nanbai Xiang Street, Ouhai District, Wenzhou, China.
Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
Arthritis Res Ther. 2024 Jan 17;26(1):26. doi: 10.1186/s13075-023-03229-x.
Primary Sjögren's syndrome (pSS) is an autoimmune condition that causes harm to exocrine glands and also has extra-glandular manifestations (EGM). pSS patients with EGM have a worse prognosis than those with only sicca symptoms. Previous studies have shown that the minor salivary glands (MSG) of pSS patients exhibit a unique profile of cytokines and chemokines compared to healthy controls. However, there is a lack of research comparing pSS with EGM (pSS-EGM) and pSS without EGM (pSS-non-EGM). This study aims to explore potential biomarkers associated with pSS, particularly pSS with EGM.
By utilizing RNA sequencing, we conducted an analysis on the gene expression profiles of MSG in 63 patients diagnosed with pSS, as well as 12 non-pSS individuals. Furthermore, we also investigated the MSG of pSS patients, both with and without EGM. Through bioinformatics analysis, we identified genes with differential expression (DEGs) and determined the core hub genes using PPI network. We then analyzed the top 20 DEGs and their correlation with the patients' clinical characteristics, and validated our findings using peripheral blood plasma.
A total of 725 differentially expressed genes (DEGs) were identified in the comparison between pSS and non-pSS groups, and 727 DEGs were observed between pSS-EGM and pSS-non-EGM. It is noteworthy that the expression levels of CXCL9 were higher in both pSS patients and pSS-EGM when compared to the control group. Taking into consideration the significance of the top 20 DEGs in relation to clinical parameters and the central hub genes, we ultimately chose CXCL9. In comparison to the non-pSS group, pSS patients exhibited notably greater expression of the CXCL9 gene in the MSG, as well as higher levels of CXCL9 protein in their plasma (p < 0.001). Furthermore, the expression of the CXCL9 gene and levels of CXCL9 protein were notably higher in pSS patients accompanied by EGM and those with SSA antibodies. Additionally, a correlation was found between the expression of the CXCL9 gene and the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), as well as with immunoglobulin G (IgG) levels and erythrocyte sedimentation rate (ESR). Meanwhile, the protein levels of CXCL9 were found to be correlated with IgG levels and ESSDAI.
CXCL9 proves to be a valuable biomarker in pSS, specifically due to its strong ability to differentiate between pSS patients with EGM and those without EGM. There is a significant correlation between CXCL9 and various clinical parameters both at the gene and protein level. Therefore, CXCL9 could be a potential target for future treatment of pSS.
原发性干燥综合征（pSS）是一种自身免疫性疾病，会损害外分泌腺，也有腺外表现（EGM）。有 EGM 的 pSS 患者比仅有干燥症状的患者预后更差。先前的研究表明，与健康对照组相比，pSS 患者的小唾液腺（MSG）表现出独特的细胞因子和趋化因子谱。然而，目前缺乏比较有 EGM（pSS-EGM）和无 EGM（pSS-non-EGM）的 pSS 患者的研究。本研究旨在探索与 pSS 相关的潜在生物标志物，特别是与 pSS-EGM 相关的生物标志物。
通过 RNA 测序，我们对 63 例 pSS 患者和 12 例非 pSS 个体的 MSG 基因表达谱进行了分析。此外，我们还研究了有和无 EGM 的 pSS 患者的 MSG。通过生物信息学分析，我们确定了差异表达基因（DEGs），并使用 PPI 网络确定了核心枢纽基因。然后，我们分析了前 20 个 DEG 及其与患者临床特征的相关性，并使用外周血浆进行了验证。
在 pSS 与非 pSS 组之间的比较中，共鉴定出 725 个差异表达基因（DEGs），在 pSS-EGM 与 pSS-non-EGM 之间鉴定出 727 个 DEGs。值得注意的是，与对照组相比，pSS 患者和 pSS-EGM 患者的 CXCL9 表达水平均较高。考虑到 top20 DEGs 与临床参数和中心枢纽基因的相关性，我们最终选择了 CXCL9。与非 pSS 组相比，pSS 患者的 MSG 中 CXCL9 基因表达显著增加，其血浆中 CXCL9 蛋白水平也显著升高（p<0.001）。此外，在伴有 EGM 和 SSA 抗体的 pSS 患者中，CXCL9 基因的表达和 CXCL9 蛋白水平显著升高。此外，还发现 CXCL9 基因的表达与 EULAR 干燥综合征疾病活动指数（ESSDAI）以及免疫球蛋白 G（IgG）水平和红细胞沉降率（ESR）之间存在相关性。同时，在基因和蛋白水平上，CXCL9 蛋白水平与 IgG 水平和 ESSDAI 呈正相关。
CXCL9 是 pSS 的一个有价值的生物标志物，特别是因为它能够很好地区分有 EGM 和无 EGM 的 pSS 患者。CXCL9 基因和蛋白水平与多种临床参数均有显著相关性。因此，CXCL9 可能成为 pSS 未来治疗的潜在靶点。
