Abundant glutamic acid decarboxylase (GAD)‐reactive B cells in gad‐antibody–associated neurological disorders

Abstract

High levels of antibodies against glutamic acid decarboxylase (GAD) are observed in patients with different neurological disorders, but cells producing these autoantibodies are largely unexplored. We detect circulating GAD‐reactive B cells in peripheral blood that readily differentiate into antibody‐producing cells. These cells are highly elevated in most patients with GAD‐antibody–associated disorders (n = 15) compared to controls (n = 19). They mainly produce GAD65 antibodies of the IgG1 and IgG4 subclasses and are as abundant as B cells reactive for common recall antigens. Bone marrow cells represent an additional source of GAD antibodies. The identification of GAD‐antibody–producing cells has implications for the selection of cell‐specific biologics. ANN NEUROL 2019;85:448–454.

Identification of circulating MOG-specific B cells in patients with MOG antibodies

“…This reveals a difference to GAD65 autoimmunity, where GAD65-specific B cells were as abundant as B cells specific for recall antigens. 19…”

“…However, despite immunosuppressive treatment, patients had circulating MOG-Abs and also MOG-specific B cells in blood, consistent with other studies examining B cells of treated patients with other autoantibodies. 19,28,29 Furthermore, we had the chance to analyze blood cells from 6 patients with MOG-Abs before the onset of treatment, and these patients are very similar to the total cohort of patients in terms of abundance of MOG-specific B cells and lack of correlation between serum anti-MOG and circulating MOG-specific B cells.…”

“…18 The in vitro stimulation we use in this study induces the production of IgG, IgA, and IgM. 18,19 For limiting dilution assays, PBMCs were distributed from 10 3 to 10 5 cells/well in 200 μL and stimulated for 11 days. The frequency of antigen-specific B cells was calculated according to the Poisson distribution.…”

“…The frequency of antigen-specific B cells was calculated according to the Poisson distribution. 18,19 Total B-cell frequency was determined by flow cytometry using the anti-human CD19-PerCP-Cy5.5 Ab (SJ25C1; eBioscience, San Diego, CA).…”

Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS

“…A consensus is emerging that despite these clinically different features, patients with MOG-Abs should be grouped as a separate disease [44,81]. Also, patients with anti-GAD65 show different neurological syndromes like stiff person syndrome, cerebellar ataxia, limbic encephalitis, epilepsy, or oculomotor dysfunction [38,71]. The different localizations of OMGP and our animal model, showing that autoimmunity to OMGP can result in cortical encephalitis/meningitis, lesions in the spinal cord and may pave the way for demyelination by antibodies of a different specificity, might explain why different clinical features can be associated with autoimmunity to OMGP.…”