系统性红斑狼疮中加速的免疫衰老：当前证据与临床转化
Accelerated immunosenescence in SLE: current evidence and clinical translation.
摘要(中文译文)
系统性红斑狼疮（SLE）患者常在年轻时就出现与年龄相关的不良结局，这提示免疫衰老过程可能与慢性免疫激活、治疗暴露和累积损伤相互作用，共同塑造长期疾病负担。尽管在类风湿关节炎和慢性病毒感染（如HIV/CMV）中也报道了免疫年龄加速现象，但SLE尤其适合作为炎症驱动免疫衰老的人类模型，因为其典型发病于年轻女性，且衰老特征在临床、细胞和分子层面汇聚一致。本综述综合了SLE中加速免疫衰老的证据，涵盖全身表现、免疫细胞重塑和分子衰老标志物。在临床上，SLE与早发心血管疾病、衰弱、认知障碍、严重感染和疫苗反应性降低相关。在免疫学上，衰老样免疫亚群（包括终末分化T细胞、年龄相关/双阴性B细胞、功能失调的NK细胞和衰老样髓系细胞）过早扩增。分子特征包括类炎性衰老细胞因子模式、端粒磨损和表观遗传年龄加速。我们还讨论了一个转化框架，利用免疫表型分析、端粒/表观遗传时钟和复合免疫时钟来量化免疫衰老，并探讨其在风险分层、治疗决策和监测免疫重编程策略中的潜在应用。加速免疫衰老为理解SLE在全身、细胞和分子层面的异质性提供了一个生物学上合理且具有临床相关性的框架。然而，免疫衰老指标目前应被视为候选研究生物标志物，而非经过验证的临床决策工具。需要针对SLE的前瞻性研究来确定其预测价值、疾病特异性和临床效用。
Abstract
Patients with systemic lupus erythematosus (SLE) often develop age-related adverse outcomes at a young age, raising the possibility that immune-aging processes may interact with chronic immune activation, treatment exposure, and accumulated damage in shaping long-term disease burden. Although immune-age acceleration has also been reported in rheumatoid arthritis and chronic viral infections (e.g., HIV/CMV), SLE is particularly well suited as a human model of inflammation-driven immune aging because of its typical onset in young women and the convergence of aging signatures across clinical, cellular, and molecular levels. This review synthesizes evidence for accelerated immunosenescence in SLE across systemic manifestations, immune cell remodeling, and molecular senescence markers. Clinically, SLE is linked to premature cardiovascular disease, frailty, cognitive impairment, severe infections, and reduced vaccine responsiveness. Immunologically, senescent-like immune subsets (including terminally differentiated T cells, age-associated/double-negative B cells, dysfunctional NK cells, and senescence-like myeloid cells) expand prematurely. Molecular features include inflammaging-like cytokine patterns, telomere attrition, and epigenetic age acceleration. We also discuss a translational framework for quantifying immunosenescence using immunophenotyping, telomere/epigenetic clocks, and composite immune clocks, with potential applications in risk stratification, treatment decisions, and monitoring immune-reprogramming strategies. Accelerated immunosenescence provides a biologically plausible and clinically relevant framework for understanding SLE heterogeneity across systemic, cellular, and molecular levels. However, immune-aging measures should currently be regarded as candidate research biomarkers rather than validated clinical decision tools. Prospective SLE-specific studies are needed to establish their predictive value, disease specificity, and clinical utility.
如何引用
AMA
Qingshuang Li, Wei Zhang, Yulan Chen, Jing Du. Accelerated immunosenescence in SLE: current evidence and clinical translation.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1830804.
APA
Qingshuang Li, Wei Zhang, Yulan Chen, Jing Du (2026). Accelerated immunosenescence in SLE: current evidence and clinical translation.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1830804
GB/T 7714
Qingshuang Li, Wei Zhang, Yulan Chen, Jing Du. Accelerated immunosenescence in SLE: current evidence and clinical translation.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1830804.
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