Table_7_Predicted Disease-Specific Immune Infiltration Patterns Decode the Potential Mechanisms of Long Non-Coding RNAs in Primary Sjogren’s Syndrome.xlsx

Primary Sjogren’s syndrome (pSS) is a chronic progressive autoimmune disease with clinical phenotypic “Sicca symptoms”. In some cases, the diagnosis of pSS is delayed by 6–7 years due to the inefficient differential diagnosis of pSS and non-SS “Sicca”. This study aimed to investigate the difference between these two diseases, and in particular, their immunopathogenesis. Based on their gene expression profiles, we systematically defined for the first time the predicted disease-specific immune infiltration pattern of patients with pSS differentiated from normal donors and patients with non-SS “Sicca”. We found that it was characterized by the aberrant abundance and interaction of tissue-infiltrated immune cells, such as a notable shift in the subpopulation of six immune cells and the perturbed abundance of nine subpopulations, such as CD4+ memory, CD8+ T-cells and gamma delta T-cells. In addition, we identified essential genes, particularly long non-coding RNAs (lncRNAs), as the potential mechanisms linked to this predicted pattern reprogramming. Fourteen lncRNAs were identified as the potential regulators associated with the pSS-specific immune infiltration pattern in a synergistic manner, among which the CTA-250D10.23 lncRNA was highly relevant to chemokine signaling pathways. In conclusion, aberrant predicted disease-specific immune infiltration patterns and relevant genes revealed the immunopathogenesis of pSS and provided some clues for the immunotherapy by targeting specific immune cells and genes.

原发性干燥综合征（Primary Sjogren’s syndrome, pSS）是一类以“干燥症状（Sicca symptoms）”为临床表型的慢性进展性自身免疫疾病。部分病例因pSS与非干燥综合征（non-SS）相关“干燥症状”的鉴别诊断效率低下，导致确诊延迟6~7年。本研究旨在探究这两类疾病的差异，尤其是其免疫发病机制。基于基因表达谱，我们首次系统性明确了pSS患者相较于正常供体及非SS相关干燥症状患者的疾病特异性免疫浸润预测模式：该模式以组织浸润免疫细胞的异常丰度及相互作用为特征，具体表现为6种免疫细胞亚群的显著偏移，以及CD4+记忆性T细胞、CD8+T细胞、γδT细胞等9种免疫细胞亚群的丰度紊乱。此外，我们鉴定出关键基因，尤其是长链非编码RNA（long non-coding RNAs, lncRNAs），作为与该预测模式重编程相关的潜在机制。本研究协同鉴定出14个与pSS特异性免疫浸润模式相关的潜在调控长链非编码RNA，其中CTA-250D10.23长链非编码RNA与趋化因子信号通路高度相关。综上，本研究揭示的异常疾病特异性免疫浸润模式及相关基因，阐明了pSS的免疫发病机制，并为靶向特定免疫细胞与基因的免疫治疗提供了新线索。