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Long-lived plasma cells and memory B cells produce pathogenic anti-GAD65 autoantibodies in Stiff Person Syndrome

Rizzi, Marta and Knoth, Rolf and Hampe, Christiane S. and Lorenz, Peter and Gougeon, Marie-Lise and Lemercier, Brigitte and Venhoff, Nils and Ferrera, Francesca and Salzer, Ulrich and Thiesen, Hans-Jürgen and Peter, Hans-Hartmut and Walker, Ulrich A. and Eibel, Hermann. (2010) Long-lived plasma cells and memory B cells produce pathogenic anti-GAD65 autoantibodies in Stiff Person Syndrome. PLoS ONE, Vol. 5, H. 5 , e10838.

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Official URL: http://edoc.unibas.ch/dok/A6005136

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Rheumatologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Rheumatologie
UniBasel Contributors:Walker, Ulrich A.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Aug 2018 06:40
Deposited On:21 Jun 2013 12:28

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