CTLA-4在干燥综合征中的作用和功能
The role and function of CTLA-4 in Sjögren's syndrome.
摘要(中文译文)
细胞毒性T淋巴细胞相关抗原4（CTLA-4）是参与免疫调节的关键免疫检查点。CTLA-4抑制剂已广泛应用于肿瘤治疗，近年来在干燥综合征（SS）等自身免疫性疾病中受到越来越多的关注。CTLA-4调控多种免疫过程，包括遗传易感性、免疫细胞亚群及炎症细胞因子水平。CTLA-4与程序性细胞死亡蛋白1（PD-1）、含Ig和ITIM结构域的T细胞免疫受体（TIGIT）及含T细胞免疫球蛋白和黏蛋白结构域蛋白3（TIM-3）等共抑制受体共同构成多层免疫抑制网络。它调节T细胞亚群的平衡，调控B细胞受体（BCR）相关通路及布鲁顿酪氨酸激酶（BTK）等下游分子，从而协调细胞免疫与体液免疫。用于肿瘤免疫治疗的CTLA-4抑制剂可能引发类似干燥综合征的免疫相关不良事件。阿巴西普（Abatacept）是一种阻断T细胞共刺激的CTLA-4-Ig融合蛋白，已被研究作为原发性干燥综合征（pSS）的候选治疗药物。开放标签临床研究一致表明，阿巴西普可降低疾病活动度、改善唾液腺功能并缓解全身症状。然而，随机对照试验的结果仍不一致：部分研究显示与安慰剂相比无显著临床获益，而另一些研究则显示临床指标、患者报告结局及实验室参数均有改善。目前，CTLA-4在干燥综合征发病机制中的确切作用尚未完全阐明，支持CTLA-4靶向治疗的高质量证据仍然有限。仍需进一步研究以验证阿巴西普及其他CTLA-4调节剂在干燥综合征中的治疗价值及最佳应用。
Abstract
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a key immune checkpoint involved in immune regulation. CTLA-4 inhibitors have been widely used in cancer therapy and have attracted increasing attention in autoimmune diseases such as Sjögren's syndrome (SS) in recent years. CTLA-4 modulates multiple immune processes, including genetic susceptibility, immune cell subsets, and inflammatory cytokine levels. CTLA-4, together with co-inhibitory receptors including Programmed cell death protein 1 (PD-1), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), forms a multi-layered immunosuppressive network. It modulates the balance of T cell subsets, regulates B cell receptor (BCR)-related pathways and downstream molecules such as Bruton's tyrosine kinase (BTK), and thereby orchestrates cellular and humoral immunity. CTLA-4 inhibitors used in cancer immunotherapy may trigger immune-related adverse events resembling Sjögren's syndrome. Abatacept, a CTLA-4-Ig fusion protein that blocks T-cell costimulation, has been investigated as a therapeutic candidate for primary Sjögren's syndrome (pSS). Open-label clinical studies consistently indicate that abatacept reduces disease activity, improves salivary gland function, and alleviates systemic symptoms. However, findings from randomized controlled trials remain inconsistent: some show no significant clinical benefit compared with placebo, whereas others demonstrate improvements in clinical indices, patient-reported outcomes, and laboratory parameters. Currently, the precise mechanism of CTLA-4 in the pathogenesis of Sjögren's syndrome\ remains incompletely clarified, and high-quality evidence supporting CTLA-4-targeted therapy is still limited. Further research is needed to validate the therapeutic value and optimal application of abatacept and other CTLA-4-modulating agents in Sjögren's syndrome.
如何引用
AMA
Ji Wen, Lingshu Zhang, Linshen Xie, Dingzi Zhou, Menglin Chen. The role and function of CTLA-4 in Sjögren's syndrome.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1868113.
APA
Ji Wen, Lingshu Zhang, Linshen Xie, Dingzi Zhou, Menglin Chen (2026). The role and function of CTLA-4 in Sjögren's syndrome.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1868113
GB/T 7714
Ji Wen, Lingshu Zhang, Linshen Xie, Dingzi Zhou, Menglin Chen. The role and function of CTLA-4 in Sjögren's syndrome.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1868113.
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