Eculizumab (ECU), a C5 complement inhibitor, is approved to treat acetylcholine receptor autoantibody positive generalized myasthenia gravis (AChR MG). The clinical effect of ECU relies on inhibition of the terminal complement complex; however, the effect of ECU on lymphocytes is largely unknown. We evaluated innate and adaptive immunity among AChR MG patients (N = 3) before ECU and ≥3 months later while on stable therapy, and found reduced activation markers in memory CD4⁺ T cell subsets, increased regulatory T cell populations, and reduced frequencies of CXCR5⁺HLA-DR⁺CCR7⁺ Tfh subsets and CD11b⁺ migratory memory B cells. We observed increases within CD8⁺ T cell subsets that were terminally differentiated and senescent. Our data suggest complement inhibition with ECU modulates the adaptive immunity in patients with MG, consistent with preclinical data showing changes in complement-mediated signaling by T- and antigen-presenting cells. These findings extend our understanding of ECU's mechanism of action when treating patients with MG.

Eculizumab (ECU) 是一种 C5 补体抑制剂，被批准用于治疗乙酰胆碱受体自身抗体阳性的全身性重症肌无力 (AChR MG)。ECU的临床效果依赖于对末端补体复合物的抑制；然而，ECU 对淋巴细胞的影响在很大程度上是未知的。我们 在 ECU 之前和≥3 个月后在稳定治疗期间评估了 AChR MG 患者 ( N = 3) 的先天免疫和适应性免疫，发现记忆 CD4 ⁺ T 细胞亚群中的激活标志物减少，调节性 T 细胞群增加，以及减少的频率CXCR5 ⁺ HLA-DR ⁺ CCR7 ⁺ Tfh 子集和 CD11b ⁺迁移记忆 B 细胞。我们观察到 CD8 ⁺终末分化和衰老的 T 细胞亚群。我们的数据表明，ECU 抑制补体可调节 MG 患者的适应性免疫，这与显示 T 和抗原呈递细胞补体介导的信号传导发生变化的临床前数据一致。这些发现扩展了我们对治疗 MG 患者时 ECU 作用机制的理解。