Dissection of complement and Fc-receptor-mediated pathomechanisms of autoantibodies to myelin oligodendrocyte glycoprotein

Mader S, Ho S, Wong HK, Baier S, Winklmeier S, Riemer CD, Rübsamen H, Fernandez IM, Gerhards R, Du C, Chuquisana O, Lünemann JD, Lux A, Nimmerjahn F, Bradl M, Kawakami N, Meinl E (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 120

Pages Range: e2300648120

Journal Issue: 13

DOI: 10.1073/pnas.2300648120

Abstract

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) have recently been established to define a new disease entity, MOG-antibody-associated disease (MOGAD), which is clinically overlapping with multiple sclerosis. MOG-specific antibodies (Abs) from patients are pathogenic, but the precise effector mechanisms are currently still unknown and no therapy is approved for MOGAD. Here, we determined the contributions of complement and Fc-receptor (FcR)-mediated effects in the pathogenicity of MOG-Abs. Starting from a recombinant anti-MOG (mAb) with human IgG1 Fc, we established MOG-specific mutant mAbs with differential FcR and C1q binding. We then applied selected mutants of this MOG-mAb in two animal models of experimental autoimmune encephalomyelitis. First, we found MOG-mAb-induced demyelination was mediated by both complement and FcRs about equally. Second, we found that MOG-Abs enhanced activation of cognate MOG-specific T cells in the central nervous system (CNS), which was dependent on FcR-, but not C1q-binding. The identification of complement-dependent and -independent pathomechanisms of MOG-Abs has implications for therapeutic strategies in MOGAD.

Authors with CRIS profile

Carolina Daniela Riemer Lehrstuhl für Genetik Anja Lux Lehrstuhl für Genetik Falk Nimmerjahn Lehrstuhl für Genetik

Involved external institutions

Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Universitätsklinikum Münster DE Germany (DE) Medizinische Universität Wien AT Austria (AT)

How to cite

APA:

Mader, S., Ho, S., Wong, H.K., Baier, S., Winklmeier, S., Riemer, C.D.,... Meinl, E. (2023). Dissection of complement and Fc-receptor-mediated pathomechanisms of autoantibodies to myelin oligodendrocyte glycoprotein. Proceedings of the National Academy of Sciences of the United States of America, 120(13), e2300648120. https://dx.doi.org/10.1073/pnas.2300648120

MLA:

Mader, Simone, et al. "Dissection of complement and Fc-receptor-mediated pathomechanisms of autoantibodies to myelin oligodendrocyte glycoprotein." Proceedings of the National Academy of Sciences of the United States of America 120.13 (2023): e2300648120.

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