MOG-IgA as a Potential Marker of Germinal Center Activity—Reply

Abstract

COMMENT & RESPONSEIn Reply We thank Handel and colleagues for their interest and thoughtful comments on our article. The authors addressed the role of autoantigen-reactive immunoglobulin A (IgA) antibodies as markers of germinal center (GC)-based immunoglobulin class-switching and the importance of longitudinal testing for myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) and M (IgM) in patients seropositive for MOG-IgA.Upon the identification of isolated and coexisting MOG-IgA in patients with demyelinating central nervous system disease, we suggested that differences in the inflammatory milieu in the context of the type and site of preceding infections or vaccinations may account for the diverse immunoglobulin responses. 1 Indeed, most patients belonging to the isolated MOG-IgA group presented clinical attacks after recent infection or vaccination. This supports the hypothesis of infectious triggers being directly involved in MOG-specific IgA generation, a process that can be GC dependent or independent (the latter particularly in mucosal tissues). 2,3 In that regard, MOG-IgA as a potential marker for ongoing GC-based immunoglobulin class-switching is an interesting hypothesis raised by Handel and colleagues, especially in patients with coexisting MOG-IgG or MOG-IgM antibodies. Although ongoing GCbased immunoglobulin class-switching has previously been suggested for coexisting N-methyl-D-aspartate receptor (NMDAR) IgA in patients with NMDAR-IgG or NMDAR-IgM in the context of intratumoral tertiary lymphoid structures in teratomas and in cervical lymph nodes, 4,5 the reported frequency of teratomas in patients positive for MOG immunoglobulin, including our cohort, is low. 1,6 Further, the relevance of GC activity in patients with isolated IgA autoantibodies remains unclear. Yet, although we did not detect seroconversion in patients longitudinally followed up who were seropositive for MOG-IgG, MOG-IgA, and/or MOG-IgM, we cannot exclude class-switching before the first sample time point for patients with an earlier disease onset.Regarding future studies, the longitudinal assessment of MOG immunoglobulin serostatus as proposed by Handel and colleagues, especially in the MOG-IgG and MOG-IgA doubleseropositive group, will shed light on sites and mechanisms of the divergent immunoglobulin responses. In our study, the sample size was not sufficient to look at treatment response to anti-CD20. 1 Hence, clinical studies assessing responsiveness to B-cell targeting therapies and immunophenotypic studies of cervical lymph nodes in patients positive for MOG immunoglobulins are needed to guide treatment strategies.