Epigenetic mechanisms have been implicated in the pathogenesis of Sjögren’s syndrome (SS). Extensive alterations in DNA methylation have been described in minor salivary gland (MSG) epithelial cells and lymphocytes derived from SS patients compared to sicca controls. In an effort to identify novel potential epigenetic markers that could prove useful in diagnosis and disease monitoring, we explored whether DNA methylation differences can also be detected in saliva from SS patients compared to sicca controls. We performed DNA methylation analysis by methylation‐sensitive restriction digestion followed by quantitative real‐time polymerase chain reaction of selected genomic loci in saliva samples of 16 SS patients and 10 sicca controls with negative MSG biopsy. We identified reduced DNA methylation of the imprinting control region (ICR) of the H19 locus in SS patient saliva compared to sicca controls. Levels of saliva H19 ICR methylation were negatively correlated with C4 serum complement levels. Consistent with the reduced methylation of the ICR, H19 RNA levels were increased in SS patient peripheral blood mononuclear cells (PBMCs), while no significant change was observed in MSG H19 RNA levels compared to sicca controls. Our findings support that H19 ICR methylation could be a useful molecular epigenetic marker in monitoring patients with SS, highlighting saliva as a valuable biological sample in SS research and clinical practice. The role of H19 in SS pathogenesis remains to be addressed.

中文翻译：

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干燥综合征患者唾液的表观遗传改变。

表观遗传机制已经牵涉到干燥综合征（SS）的发病机理。与干燥剂对照相比，SS患者的小唾液腺（MSG）上皮细胞和淋巴细胞中已经描述了DNA甲基化的广泛改变。为了确定可能被证明对诊断和疾病监测有用的新的潜在表观遗传标记，我们探索了与干燥对照相比，SS患者唾液中是否还可以检测到DNA甲基化差异。我们通过甲基化敏感的限制性酶切消化，然后对MSG活检阴性的16名SS患者和10例干燥对照的唾液样本中的选定基因组位点进行定量实时聚合酶链反应，进行了DNA甲基化分析。我们确定了减少的DNA甲基化的印记控制区（ICR）与干燥对照相比，SS患者唾液中的H19基因座。唾液H19 ICR甲基化水平与C4血清补体水平呈负相关。与ICR的还原甲基化保持一致，H19 RNA水平在SS患者的外周血单核细胞（PBMC）中增加，而在MSG中没有观察到变化显著H19 RNA水平相比于对照结膜炎。我们的研究结果支持H19 ICR甲基化可能是监测SS患者的有用的分子表观遗传标记，强调唾液是SS研究和临床实践中有价值的生物学样品。H19在SS发病机理中的作用仍有待解决。