自身抗体
抗体依赖性细胞介导的细胞毒性
免疫学
细胞毒性
医学
细胞毒性T细胞
抗体
多发性硬化
病理
生物
单克隆抗体
体外
生物化学
作者
Soumya Yandamuri,Beata Filipek,Abeer Obaid,Nikhil Lele,Joshua M. Thurman,Naila Makhani,Richard J. Nowak,Youguang Guo,Claudia F. Lucchinetti,Eoin P. Flanagan,Erin E. Longbrake,Kevin O’Connor
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2023-06-08
卷期号:8 (11)
被引量:4
标识
DOI:10.1172/jci.insight.165373
摘要
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an inflammatory demyelinating CNS condition characterized by the presence of MOG autoantibodies. We sought to investigate whether human MOG autoantibodies are capable of mediating damage to MOG-expressing cells through multiple mechanisms. We developed high-throughput assays to measure complement activity (CA), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity (ADCC) of live MOG-expressing cells. MOGAD patient sera effectively mediate all of these effector functions. Our collective analyses reveal that (a) cytotoxicity is not incumbent on MOG autoantibody quantity alone; (b) engagement of effector functions by MOGAD patient serum is bimodal, with some sera exhibiting cytotoxic capacity while others did not; (c) the magnitude of CDC and ADCP is elevated closer to relapse, while MOG-IgG binding is not; and (d) all IgG subclasses can damage MOG-expressing cells. Histopathology from a representative MOGAD case revealed congruence between lesion histology and serum CDC and ADCP, and we identified NK cells, mediators of ADCC, in the cerebrospinal fluid of relapsing patients with MOGAD. Thus, MOGAD-derived autoantibodies are cytotoxic to MOG-expressing cells through multiple mechanisms, and assays quantifying CDC and ADCP may prove to be effective tools for predicting risk of future relapses.
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