Abundant GAD-reactive B cells in GAD-antibody-associated neurological disorders.
Ann Neurol. 2019 Jan 11. doi: 10.1002/ana.25414. [Epub ahead of print]
|Authors/Editors:||Thaler FS, Thaller AL, Biljecki M, Schuh E, Winklmeier S, Mahler CF, Gerhards R, Völk S, Schnorfeil F, Subklewe M, Hohlfeld R, Kümpfel T, Meinl E.|
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.