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Home/Research/Paper Chase/B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients.
B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients.
Proc. Natl. Acad. Sci. U.S.A..Sep 2, 2008;105(35):13009-14.
Gavanescu I, Benoist C, Mathis D.
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Autoimmune regulator (Aire)-deficient mice and humans have circulating autoantibodies against a multitude of organs and multiorgan autoinflammatory infiltrates. It is not known to what extent autoantibodies or their source, B lymphocytes, are required for disease onset or progression. We show in this research that B cells must be present for Aire-deficient mice to develop fulminant infiltrates. We found no evidence that autoantibodies were directly pathogenic; rather, B cells appeared to play a critical early role in T cell priming or expansion. A therapeutic reagent directed against B cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).