Humoral signatures of MOG-antibody-associated disease track with age and disease activity

• DOI: 10.1016/j.xcrm.2022.100913
• Publication Date: 2023-01-19T16:46:59Z
• Authors: Marianna Spatola; Omar Chuquisana; Wonyeong Jung; Joseph A. Lopez; Eva-Maria Wendel; Sudarshini Ramana...; Christian W. Keller; Tim Hahn; Edgar Meinl; Markus Reindl; Russell C. Dale; Heinz Wiendl; Douglas A. Lauffe...; Kevin Rostásy; Fabienne Brilot; Galit Alter; Jan D. Lünemann
• Keywords: Myelin oligodendrocyte glycoprotein; Endophenotype

Myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated disease (MOGAD) is an inflammatory demyelinating of the CNS. Although MOG encephalitogenic in different mammalian species, mechanisms by which human MOG-specific Abs contribute to MOGAD are poorly understood. Here, we use a systems-level approach combined with high-dimensional characterization Ab-associated immune features deeply profile humoral responses 123 patients MOGAD. We show that age major determinant for MOG-antibody-related signatures. Unsupervised clustering additionally identifies two dominant immunological endophenotypes The pro-inflammatory endophenotype characterized increased binding affinities activating Fcγ receptors (FcγRs), capacity activate innate cells, and decreased frequencies galactosylated sialylated immunoglobulin G (IgG) glycovariants associated clinically active disease. Our data support concept FcγR-mediated effector functions control pathogenicity IgG suggest FcγR-targeting therapies should be explored their therapeutic potential