AQP4 and MOG Characterize the Autoantibody Landscape of Checkpoint Blockade-Induced Optic Neuritis.

Authors

Tong Wu, Yongluo Jiang, Jiacai Lin, Jingyao Zhang, Ao Zhang, Guanqing Zhong, Guangmin Jian, Yiwei Xu, Pengfei Zhu, Jun Lv, Xiaochang Wu, Yang Liu, Youlong Wang, Yiming Li, Zhenyun Guo, Ningnan Fang, Xinjia Wang, Weidong Wang, Jun Lu, Ruijie Yao, Xiaoping Hong, Chenyu Yang, Shangeng Weng, Rui Wang, Rui Li, Yifei Ma

Published in

Annals of neurology. Jul 03, 2026. Epub Jul 03, 2026.

Abstract

The objective of this study was to investigate the autoantibody profile in immune checkpoint inhibitor (ICI)-induced optic neuritis (CBON) and identify key autoantibodies for diagnostic and therapeutic purposes.
In this multicenter retrospective study (January 2020-June 2025), we screened 327 neuro-ophthalmic patients from a bio-repository of 2,321 ICI-treated individuals, identifying 88 patients with CBON across 3 independent cohorts (n = 25, 29, and 34). Longitudinal serum samples (pre-ICI, prodromal, onset, and follow-up) were available for 12 patients. A matched control group of 49 ICI-treated patients without neuro-ophthalmic symptoms was included. Serum samples were analyzed using cell-based assays for 25 neural-specific IgG autoantibodies. Longitudinal samples were assessed for antibody dynamics. Correlations between serostatus and clinical features were evaluated.
Autoantibody profiling revealed a highly focused immune response concentrated against aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG). Seropositivity rates for these antibodies ranged from 17.3% to 32.4% across cohorts, whereas other neural antibodies were detected at markedly lower frequencies (<12%). Longitudinal analysis demonstrated a clear seroconversion pattern, with antibodies undetectable at pre-ICI baseline but emerging at symptom onset, which remained detectable during follow-up in a subset of patients. These AQP4/MOG antibodies were virtually absent in control patients (0-2%).
This study establishes AQP4 and MOG as the dominant autoantibodies in CBON, providing a serological framework for diagnosis and classification. The persistent antibody response following ICI-induced seroconversion offers direction for future mechanistic investigations. ANN NEUROL 2026.

PMID:
42400220
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.

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