Abstract Details

Title Phenotypes of B Cells Producing Autoantibodies in MOGAD Patients

Topic Autoimmune Neurology

Presentation(s) N1 - Neuroscience in the Clinic: Emerging Autoantibodies in Neurologic Disease (3:55 PM-4:05 PM)

Poster/Presentation
Number 002

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.

Objective To investigate phenotypes of B cells producing MOG autoantibodies and to assess autoantibodies’ capability to evoke cytotoxicity through multiple mechanisms.

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.

Authors/Disclosures
Beata A. Filipek (International Doctoral School Medical University of Lodz) PRESENTER	The institution of Ms. Filipek has received research support from National Centre of Science, Poland - Preludium Bis 2019/35/O/NZ5/02270.
Soumya S. Yandamuri, PhD (Yale School of Medicine)	Dr. Yandamuri has nothing to disclose.
Abeer Obaid	No disclosure on file
Joshua Thurman (University of Colorado)	No disclosure on file
Naila Makhani, MD (Yale University School of Medicine, Department of Pediatrics)	Dr. Makhani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Institute for Advanced Clinical Trials for Children. The institution of Dr. Makhani has received research support from NIH/NINDS. The institution of Dr. Makhani has received research support from Charles H Hood Foundation. The institution of Dr. Makhani has received research support from National Multiple Sclerosis Society. Dr. Makhani has received personal compensation in the range of $0-$499 for serving as a contributor to online content with WebMD. Dr. Makhani has received personal compensation in the range of $500-$4,999 for serving as a contributor to a CME video podcast and newsletter with eMultiple Sclerosis Review. Dr. Makhani has received personal compensation in the range of $5,000-$9,999 for serving as a consultant with I-ACT for children.
Richard J. Nowak, MD (Yale University School of Medicine)	Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Momenta . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cabaletta Bio . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cour Pharma. The institution of Dr. Nowak has received research support from Ra Pharma. The institution of Dr. Nowak has received research support from Alexion . The institution of Dr. Nowak has received research support from Momenta . The institution of Dr. Nowak has received research support from Immunovant . Dr. Nowak has received research support from argenx. Dr. Nowak has received research support from Viela Bio . Dr. Nowak has a non-compensated relationship as a Member of the Board of Directors with Myasthenia Gravis Foundation of America (MGFA) that is relevant to AAN interests or activities.
Yong Guo	No disclosure on file
Claudia F. Lucchinetti, MD, FAAN (University of De Medical School, Health Learning Blg)	The institution of Dr. Lucchinetti has received research support from Biogen Idec. The institution of Dr. Lucchinetti has received research support from NIH/NINDS. The institution of Dr. Lucchinetti has received research support from National Institute of Neurological Disorders and Stroke . The institution of Dr. Lucchinetti has received research support from National Multiple Sclerosis Society. The institution of Dr. Lucchinetti has received research support from National Center for Advancing Translational Sciences. Dr. Lucchinetti has received intellectual property interests from a discovery or technology relating to health care. Dr. Lucchinetti has a non-compensated relationship as a Member with National Institute of Neurological Disorders that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Board of Directors, Association of University Professors of Neurology that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Trustees that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Governors that is relevant to AAN interests or activities.
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic)	The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. The institution of Dr. Flanagan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from Viela Bio. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities.
Erin Longbrake, MD, PhD, FAAN (Yale University)	Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Longbrake has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Longbrake has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Longbrake has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ACTRIMS. Dr. Longbrake has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology. The institution of Dr. Longbrake has received research support from Genentech. The institution of Dr. Longbrake has received research support from Race to Erase MS. The institution of Dr. Longbrake has received research support from NINDS K23. The institution of Dr. Longbrake has received research support from Robert Patterson Leet Trust. The institution of Dr. Longbrake has received research support from Biogen. The institution of Dr. Longbrake has received research support from National MS Society. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with Department of Defense (CDMRP). Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Programmatic Review with Department of Defense (CDMRP). Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with National Institute of Health .
Kevin O'Connor (Yale University School of Medicine)	Kevin O'Connor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Kevin O'Connor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Kevin O'Connor has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Viela Bio. Kevin O'Connor has stock in Cabaletta.