Figure 1. General features of Sjögren's syndrome
尽管SS的起始诱因尚不明确，但现有研究普遍认为，其发生建立在遗传易感性与环境因素共同作用的基础之上。全基因组关联研究已确认多个与免疫调控相关的易感基因位点，包括HLA-DR、HLA-DQB1，以及IRF5、STAT4、TNFAIP3等非HLA基因。这些基因高度集中于干扰素信号、B细胞活化和炎症调控通路，提示SS的核心异常并非随机，而是指向特定免疫轴线。
在疾病早期，腺体上皮细胞被认为是免疫反应的重要“启动节点”。其可通过TLR3、TLR7、TLR9等模式识别受体感知病毒或内源性核酸信号，激活NF-κB和IRF通路，诱导Ⅰ型干扰素及多种炎症介质释放。由此，局部腺体环境迅速转变为高免疫激活状态，为后续适应性免疫反应奠定基础。
这一过程并非短暂事件，而是在免疫调控失衡的背景下持续存在，使炎症反应逐渐从局部扩展为系统性免疫异常。
近年，SS研究的显著进展并不体现在单一新分子的发现，而在于研究策略的整体转变。多组学整合分析显示，SS在分子层面具有显著异质性，不同患者在干扰素驱动程度、B细胞异常特征及免疫网络构成上存在差异。
这一认识推动了免疫分型研究的发展，也为解释既往靶向治疗研究结果不一致提供了合理框架。当前研究逐渐从“统一机制假设”转向“分层解析免疫主导因素”，为后续靶点研究和模型构建提供更加精细的依据
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