Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece.
Department of Pathology, St. Andrew General Hospital of Patras, Patras, Greece.
Autoimmun Rev. 2018 Oct;17(10):1053-1064. doi: 10.1016/j.autrev.2018.05.005. Epub 2018 Aug 10.
Sjögren's syndrome (SS) is a chronic autoimmune disease that primarily affects the exocrine glands, resulting in their functional impairment. In SS, lymphocytic infiltration of salivary and lacrimal glands, and deposition of several types of autoantibodies, mainly anti-SS-A (anti-Ro) and anti-SS-B (anti-La), lead to chronic inflammation, with xerostomia and keratoconjunctivitis sicca. In its primary form (pSS), SS does not involve additional connective tissue diseases, whereas in its secondary and more common form (sSS), SS presents in association with other rheumatic autoimmune diseases, mainly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). As in most autoimmune diseases, environmental, hormonal and genetic factors are implicated in SS pathogenesis. In SS T cells predominate in mild lesions, whereas B cells predominate in advanced lesions. Th1, Th2, Th17, follicular helper T (Tfh) cells and regulatory cells (Tregs/Bregs), with their characteristic cytokine profiles, have been implicated in the pathogenesis of SS. It has been suggested that Th1 and Th17 cells initiate SS and, as the disease progresses, Th2 and Tfh cells predominate. It is assumed that, as in all autoimmune and inflammatory conditions, tolerance defects contribute to SS pathogenesis. It is intriguing that in SS it remains unclear which types of regulatory cells are functional and whether they ameliorate or worsen the disease. In this review we present a comprehensive update on SS with emphasis on immune system involvement, and suggest new insights into SS immunopathogenesis.
干燥综合征(SS)是一种主要影响外分泌腺的慢性自身免疫性疾病,导致其功能受损。在 SS 中,唾液腺和泪腺的淋巴细胞浸润,以及几种类型的自身抗体的沉积,主要是抗 SS-A(抗 Ro)和抗 SS-B(抗 La),导致慢性炎症,出现口干和干燥性角结膜炎。在原发性(pSS)形式中,SS 不涉及其他结缔组织疾病,而在继发性(sSS)和更常见的形式中,SS 与其他风湿性自身免疫性疾病相关,主要是类风湿关节炎(RA)、系统性红斑狼疮(SLE)和系统性硬化症(SSc)。与大多数自身免疫性疾病一样,环境、激素和遗传因素都与 SS 的发病机制有关。在 SS 中,T 细胞在轻度病变中占主导地位,而 B 细胞在晚期病变中占主导地位。Th1、Th2、Th17、滤泡辅助 T(Tfh)细胞和调节细胞(Tregs/Bregs)及其特征性细胞因子谱已被牵连到 SS 的发病机制中。有研究表明 Th1 和 Th17 细胞启动 SS,随着疾病的进展,Th2 和 Tfh 细胞占主导地位。可以假设,与所有自身免疫和炎症情况一样,耐受缺陷导致 SS 的发病机制。有趣的是,在 SS 中,仍然不清楚哪种类型的调节细胞是功能性的,以及它们是改善还是恶化疾病。在这篇综述中,我们重点介绍了免疫系统参与的 SS 的全面更新,并提出了对 SS 免疫发病机制的新见解。