诊断学理论与实践 ›› 2024, Vol. 23 ›› Issue (03): 278-284.doi: 10.16150/j.1671-2870.2024.03.005

• 专家论坛 • 上一篇    下一篇

干燥综合征发病免疫机制研究现状及靶向治疗策略进展

袁祥, 厉小梅()   

  1. 中国科学技术大学附属第一医院风湿免疫科,安徽 合肥 230001
  • 收稿日期:2024-05-13 接受日期:2024-05-28 出版日期:2024-06-25 发布日期:2024-06-25
  • 通讯作者: 厉小梅 E-mail:lixiaomei@ustc.edu.cn
  • 基金资助:
    国家自然科学基金(U2120365);“科大新医学“联合基金(WK9110000148)

Advances in current research on the immunopathogenesis of Sjögren’s syndrome and targeted therapeutic strategies

YUAN Xiang, LI Xiaomei()   

  1. The Department of Rheumatology and Immunology, The First Affiliated Hospital of University of Science and Technology of China, Anhui Hefei 230001, China
  • Received:2024-05-13 Accepted:2024-05-28 Published:2024-06-25 Online:2024-06-25

摘要:

干燥综合征(Sjögren's syndrome, SS)是一种常见的全身性自身免疫性疾病,主要累及外分泌腺体,病理特征为淋巴细胞和浆细胞浸润。SS患者的主要临床表现为口干、眼干,还可出现脏器(如消化道、肺、肾脏等)受累。我国SS患病率为0.29%~0.77%,其中老年人的SS患病率为3.00%~4.00%。欧洲地区SS患病率约为0.23%。SS发病涉及多种细胞和细胞因子的相互作用,包括唾液腺上皮细胞、T细胞、B细胞、树突状细胞、干扰素(interferon, IFN)、白细胞介素(interleukin, IL)、肿瘤坏死因子(tumor necrosis factor, TNF)和炎症小体等。目前,SS的腺体治疗以局部治疗为主,系统性受累的治疗方案主要借鉴其他自身免疫性疾病,尚无获批的针对性药物。SS的靶向治疗药物中,B细胞靶向治疗药物中,研究最多的是利妥昔单抗,其对存在冷球蛋白血管炎的SS患者显示出改善唾液的疗效;BAFF抑制剂、靶向CD40和间充质干细胞等也显示了一定疗效。对于大多数存在系统损害的SS患者,糖皮质激素(glucocorticoids, GCs)是一线治疗用药。免疫抑制剂和生物制剂作为二线用药,用于GCs耐受或抵抗的SS患者。在SS的发病机制中已经确定了许多潜在的治疗靶点,但只有少部分药物可转化为临床应用。当前,需要在全面评估患者病情、借助多学科协助的基础上,联合应用现有药物,制定出相对安全、有效、不良反应较小的治疗方案。靶向治疗、低不良反应以及多药物联合仍是未来SS药物研究的重点。

关键词: 干燥综合征, 免疫机制, 靶向药物

Abstract:

Sjögren's syndrome (SS) is a prevalent systemic autoimmune disease, primarily affecting exocrine glands, characterized by lymphocyte and plasma cell infiltration. Patients typically exhibit dry mouth and eyes, with potential involvement of the digestive tract, lungs, and kidneys. In China, SS prevalence ranges from 0.29% to 0.77%, rising to 3.00%-4.00% among the elderly. In Europe, the prevalence is approximately 0.23%. The pathogenesis of SS involves interactions of multiple cells and cytokines, including salivary gland epithelial cells, T-cells, B-cells, dendritic cells, interferon (IFN), interleukin (IL), tumour necrosis factor (TNF) and inflammasomes. Currently, glandular therapy for SS is primarily localised, while treatment for systemic involvement is mainly borrowed from other autoimmune diseases, with no approved targeted drugs yet. Among the targeted therapeutic agents for SS, rituximab, a B-cell targeted therapy, is the most studied and has shown improved salivary efficacy in SS patients with cryoglobulin vasculitis. BAFF inhibitors, CD40 targeting agents, and mesenchymal stem cells have also demonstrated cartain therapeutic effects. For most systemic involvement, glucocorticoids (GCs) are the first-line treatment, while immunosuppressants and biologics serve as second-line options for GCs-tolerant or resistant patients. Although many potential therapeutic targets have been identified, few drugs have been clinically translated. Currently, there is a need to develop relatively safe and effective treatment regimens with minimal adverse effects through comprehensive patient assessment and multidisciplinary collaboration. Future SS drug research will focus on targeted therapies, adverse effects reduction, and multi-drug combinations.

Key words: Dry syndrome, Immune mechanism, Targeted drugs

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