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- Title
Long-Lived Plasma Cells and Memory B Cells Produce Pathogenic Anti-GAD65 Autoantibodies in Stiff Person Syndrome.
- Authors
Rizzi, Marta; Knoth, Rolf; Hampe, Christiane S.; Lorenz, Peter; Gougeon, Marie-Lise; Lemercier, Brigitte; Venhoff, Nils; Ferrera, Francesca; Salzer, Ulrich; Thiesen, Hans-Jürgen; Peter, Hans-Hartmut; Walker, Ulrich A.; Eibel, Hermann
- Abstract
Stiff person syndrome (SPS) is a rare, neurological disorder characterized by sudden cramps and spasms. High titers of enzyme-inhibiting IgG autoantibodies against the 65 kD isoform of glutamic acid decarboxylase (GAD65) are a hallmark of SPS, implicating an autoimmune component in the pathology of the syndrome. Studying the B cell compartment and the anti-GAD65 B cell response in two monozygotic twins suffering from SPS, who were treated with the B cell-depleting monoclonal anti-CD20 antibody rituximab, we found that the humoral autoimmune response in SPS is composed of a rituximab-sensitive part that is rapidly cleared after treatment, and a rituximab-resistant component, which persists and acts as a reservoir for autoantibodies inhibiting GAD65 enzyme activity. Our data show that these potentially pathogenic anti-GAD65 autoantibodies are secreted by long-lived plasma cells, which may either be persistent or develop from rituximabresistant memory B lymphocytes. Both subsets represent only a fraction of anti-GAD65 autoantibody secreting cells. Therefore, the identification and targeting of this compartment is a key factor for successful treatment planning of SPS and of similar autoimmune diseases.
- Subjects
PLASMA cells; AUTOANTIBODIES; DECARBOXYLASES; MONOCLONAL antibodies; RITUXIMAB; LYMPHOCYTES; SPASMS
- Publication
PLoS ONE, 2010, Vol 5, Issue 5, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0010838