Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Department of Rheumatology and Immunology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
J Autoimmun. 2023 Jul;138:103035. doi: 10.1016/j.jaut.2023.103035. Epub 2023 May 20.
Transcriptome-wide aberrant RNA editing has been shown to contribute to autoimmune diseases, but its extent and significance in primary Sjögren's syndrome (pSS) are currently poorly understood.
We systematically characterized the global pattern and clinical relevance of RNA editing in pSS by performing large-scale RNA sequencing of minor salivary gland tissues obtained from 439 pSS patients and 130 non-pSS or healthy controls.
Compared with controls, pSS patients displayed increased global RNA-editing levels, which were significantly correlated and clinically relevant to various immune features in pSS. The elevated editing levels were likely explained by significantly increased expression of adenosine deaminase acting on RNA 1 (ADAR1) p150 in pSS, which was associated with disease features. In addition, genome-wide differential RNA editing (DRE) analysis between pSS and non-pSS showed that most (249/284) DRE sites were hyper-edited in pSS, especially the top 10 DRE sites dominated by hyper-edited sites and assigned to nine unique genes involved in the inflammatory response or immune system. Interestingly, among all DRE sites, six RNA editing sites were only detected in pSS and resided in three unique genes (NLRC5, IKZF3 and JAK3). Furthermore, these six specific DRE sites with significant clinical relevance in pSS showed a strong capacity to distinguish between pSS and non-pSS, reflecting powerful diagnostic efficacy and accuracy.
These findings reveal the potential role of RNA editing in contributing to the risk of pSS and further highlight the important prognostic value and diagnostic potential of RNA editing in pSS.
转录组范围内异常的 RNA 编辑已被证明与自身免疫性疾病有关，但在原发性干燥综合征 (pSS) 中的程度和意义目前仍知之甚少。
我们通过对 439 名 pSS 患者和 130 名非 pSS 或健康对照者的小唾液腺组织进行大规模 RNA 测序，系统地描述了 pSS 中 RNA 编辑的全球模式和临床相关性。
与对照组相比，pSS 患者表现出更高的全局 RNA 编辑水平，这些水平与 pSS 中的各种免疫特征显著相关且具有临床意义。编辑水平升高的原因可能是 pSS 中腺苷脱氨酶作用于 RNA 1 (ADAR1) p150 的表达显著增加，这与疾病特征有关。此外，pSS 与非 pSS 之间的全基因组差异 RNA 编辑 (DRE) 分析显示，大多数 (249/284) DRE 位点在 pSS 中发生超编辑，特别是前 10 个 DRE 位点主要由超编辑位点组成，并分配给 9 个参与炎症反应或免疫系统的独特基因。有趣的是，在所有 DRE 位点中，有 6 个 RNA 编辑位点仅在 pSS 中检测到，且位于三个独特的基因（NLRC5、IKZF3 和 JAK3）中。此外，这些在 pSS 中具有显著临床相关性的六个特定 DRE 位点具有区分 pSS 和非 pSS 的强大能力，反映了强大的诊断功效和准确性。
这些发现揭示了 RNA 编辑在导致 pSS 风险中的潜在作用，并进一步强调了 RNA 编辑在 pSS 中的重要预后价值和诊断潜力。
