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Long-lived Plasma Cells and Memory B Cells Produce Pathogenic anti-GAD65 Autoantibodies in Stiff Person Syndrome

Marta Rizzi, Rolf Knoth, Christiane S Hampe, Peter Lorenz, Marie-Lise Gougeon, Brigitte Lemercier, Nils Venhoff, Francesca Ferrera, Ulrich Salzer, Hans-Jürgen Thiesen, Hans-Hartmut Peter, Ulrich A Walker, etc.

PLoS One. 2010 May 26;5(5):e10838.

PMID: 20520773

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 rituximab-resistant 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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4247653 Monoclonal Anti-GAD65 antibody produced in mouse Monoclonal Anti-GAD65 antibody produced in mouse Price
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