Beata Filipek1, Soumya Yandamuri2, Abeer Obaid2, Joshua Thurman3, Naila Makhani4, Richard Nowak5, Yong Guo6, Claudia Lucchinetti7, Eoin Flanagan6, Erin Longbrake8, Kevin O'Connor5
1International Doctoral School Medical University of Lodz, 2Yale School of Medicine, 3University of Colorado School of Medicine, 4Yale University School of Medicine, Department of Pediatrics, 5Yale University School of Medicine, 6Mayo Clinic, 7University of De Medical School, Health Learning Blg, 8Yale University
Objective:
To investigate phenotypes of B cells producing MOG autoantibodies and to assess autoantibodies’ capability to evoke cytotoxicity through multiple mechanisms.
Background:
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an inflammatory demyelinating central nervous system condition characterized by the presence of MOG autoantibodies. In this study, we examined phenotypes of B cells producing MOG autoantibodies and their effector functions in order to search for a clinical correlation between the properties of autoantibodies in MOGAD patients and the occurrence of relapse.
Design/Methods:
We developed high-throughput assays to assess damage to live MOG-expressing cells elicited by antibody effector functions, namely complement activity (CA), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity (ADCC). In order to determine the phenotypes of autoantibody-producing B cells, we sorted and cultured isolated B cell subtypes to assay their production of MOG autoantibodies.
Results:
MOGAD patient sera effectively mediate all of these effector functions. Moreover, we found CDC and ADCP are elevated closer to relapse and all IgG subclasses are capable of cytotoxicity to MOG-expressing cells. Multiple B cell phenotypes were capable of producing MOG autoantibodies, including activated memory, resting memory, and double negative B cells.
Conclusions:
MOGAD-derived autoantibodies are cytotoxic to MOG-expressing cells through multiple mechanisms and effector function assays should be further investigated as tools for predicting relapse.