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Impaired B Cell Expression of the Inhibitory Fcγ Receptor IIB in Myasthenia Gravis
Author(s) -
Keller Christian W.,
Chuquisana Omar,
Derdelinckx Judith,
Gross Catharina C.,
Berger Klaus,
Robinson James,
Nimmerjahn Falk,
Wiendl Heinz,
Willcox Nick,
Lünemann Jan D.
Publication year - 2022
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.26507
Subject(s) - myasthenia gravis , receptor , acetylcholine receptor , antibody , immunology , inhibitory postsynaptic potential , immunotherapy , immune system , neuromuscular junction , acetylcholine , autoimmune disease , biology , chemistry , medicine , endocrinology , neuroscience
Myasthenia gravis (MG) is an autoimmune disease in which pathogenic immunoglobulin G antibodies bind to acetylcholine receptors (or to functionally related molecules at the neuromuscular junction). B cell expression of the inhibitory immunoglobulin G receptor, Fc‐gamma receptor (FcγR) IIB, maintains peripheral immune tolerance, and its absence renders B cells hyperresponsive to autoantigen. Here, we report that FcγRIIB expression levels are substantially reduced in B lineage cells derived from immunotherapy‐naïve patients with acetylcholine receptor antibody‐positive early‐onset MG. In contrast, genetic variants associated with impaired FcγRIIB expression are not enriched in MG, indicating post‐transcriptional dysregulation. FcγR‐targeted therapies could have therapeutic benefits in MG. ANN NEUROL 2022;92:1046–1051