Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Front Immunol. 2023 Aug 10;14:1216379. doi: 10.3389/fimmu.2023.1216379. eCollection 2023.
Primary Sjogren Syndrome (pSS) is an autoimmune disease characterized by immune cell infiltration. While the presence of follicular T helper (Tfh) cells in the glandular microenvironment has been observed, their biological functions and clinical significance remain poorly understood.
We enrolled a total of 106 patients with pSS and 46 patients without pSS for this study. Clinical data and labial salivary gland (LSG) biopsies were collected from all participants. Histological staining was performed to assess the distribution of Tfh cells and B cells. Transcriptome analysis using RNA-sequencing (RNA-seq) was conducted on 56 patients with pSS and 26 patients without pSS to uncover the underlying molecular mechanisms of Tfh cells. To categorize patients, we employed the single-sample gene set enrichment analysis (ssGSEA) algorithm, dividing them into low- and high-Tfh groups. We then utilized gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and deconvolution tools to explore functional and immune infiltration differences between the low- and high-Tfh groups.
Patients with pSS had a higher positive rate of the antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB and hypergammaglobulinaemia and higher levels of serum IgG compared to the non-pSS. Histopathologic analyses revealed the presence of Tfh cells (CD4CXCR5ICOS) in germinal centers (GC) within the labial glands of pSS patients. GSEA, WGCNA, and correlation analysis indicated that the high-Tfh group was associated with an immune response related to virus-mediated IFN response and metabolic processes, primarily characterized by hypoxia, elevated glycolysis, and oxidative phosphorylation levels. In pSS, most immune cell types exhibited significantly higher infiltration levels in the high-Tfh group compared to the low-Tfh group. Additionally, patients in the Tfh-high group demonstrated a higher positive rate of the ANA, rheumatoid factor (RF), and hypergammaglobulinaemia, as well as higher serum IgG levels.
Our study suggests that Tfh cells may play a crucial role in the pathogenesis of pSS and could serve as potential therapeutic targets in pSS patients.
原发性干燥综合征（pSS）是一种以免疫细胞浸润为特征的自身免疫性疾病。虽然已经观察到滤泡辅助 T 细胞（Tfh）在腺体微环境中的存在，但它们的生物学功能和临床意义仍知之甚少。
我们共纳入 106 例 pSS 患者和 46 例非 pSS 患者进行本研究。所有参与者均采集临床资料和唇腺（LSG）活检。进行组织学染色以评估 Tfh 细胞和 B 细胞的分布。对 56 例 pSS 患者和 26 例非 pSS 患者进行 RNA 测序（RNA-seq）转录组分析，以揭示 Tfh 细胞的潜在分子机制。为了对患者进行分类，我们采用了单样本基因集富集分析（ssGSEA）算法，将其分为低 Tfh 组和高 Tfh 组。然后我们利用基因集富集分析（GSEA）、加权基因共表达网络分析（WGCNA）和去卷积工具，探索低 Tfh 组和高 Tfh 组之间的功能和免疫浸润差异。
与非 pSS 患者相比，pSS 患者的抗核抗体（ANA）、抗 Ro52、抗 SSA、抗 SSB 和高丙种球蛋白血症阳性率更高，血清 IgG 水平也更高。组织病理学分析显示，pSS 患者唇腺的生发中心（GC）内存在 Tfh 细胞（CD4+CXCR5+ICOS）。GSEA、WGCNA 和相关性分析表明，高 Tfh 组与病毒介导的 IFN 反应和代谢过程相关的免疫反应有关，主要特征为缺氧、糖酵解和氧化磷酸化水平升高。在 pSS 中，与低 Tfh 组相比，大多数免疫细胞类型在高 Tfh 组中的浸润水平显著升高。此外，Tfh-high 组患者的 ANA、类风湿因子（RF）和高丙种球蛋白血症阳性率以及血清 IgG 水平均更高。
我们的研究表明，Tfh 细胞可能在 pSS 的发病机制中发挥关键作用，并可能成为 pSS 患者的潜在治疗靶点。
