Brain Advance Access originally published online on May 12, 2008
Brain 2008 131(6):1455-1463; doi:10.1093/brain/awn077
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Interferon-β increases BAFF levels in multiple sclerosis: implications for B cell autoimmunity
1Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, 2Institute for Clinical Neuroimmunology, Ludwig-Maximilians-Universität, Munich, 3Marianne-Strauß-Klinik, Berg and 4Department for Dermatology, University of Regensburg, Regensburg, Germany
Correspondence to: Dr. Edgar Meinl, Department of Neuroimmunology, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany E-mail: meinl{at}neuro.mpg.de
B cells are increasingly recognized as major players in multiple sclerosis pathogenesis. The BAFF/APRIL system is crucial for B cell homoeostasis and may drive B cell-dependent autoimmunity. We asked whether this system is affected by Interferon (IFN)-β therapy. We analysed transcription of the ligands (BAFF, APRIL, TWE-PRIL) and the corresponding receptors (BAFF-R, TACI and BCMA) by TaqMan-PCR ex vivo in whole blood and in immune cell subsets purified from IFN-β-treated multiple sclerosis patients. Serum BAFF concentrations were determined by ELISA. This cross-sectional study involved 107 donors. IFN-β therapy strongly induced BAFF transcription proportionally to the IFN-β biomarker MxA in monocytes and granulocytes in vivo. BAFF serum concentrations were elevated in IFN-β-treated multiple sclerosis patients to a similar level as observed in SLE patients. In cultured PBMC, neutrophils, fibroblasts and astrocytes, BAFF was induced by IFN-β concentrations similar to those reached in vivo in treated multiple sclerosis patients. BAFF turned out to be the main regulated element of the BAFF/APRIL system. In untreated multiple sclerosis patients, there was no BAFF increase as compared to healthy controls. Our study reveals a complex situation. We show that IFN-β therapy induces a potent B cell survival factor, BAFF. However, B cell depletion would be desirable at least in some multiple sclerosis patients. The systemic induction of BAFF by IFN-β therapy may facilitate the production of various autoantibodies and of IFN-neutralizing antibodies. Individual MS/NMO patients who have major B cell involvement may benefit less than others from IFN-β therapy, thus explaining interindividual differences of the therapeutic response.
Key Words: autoantibodies; B cells; interferon; multiple sclerosis therapy
Abbreviations: APRIL, a proliferation-inducing ligand; BAFF, B cell activating factor of the TNF family; IFN, Interferon; Ig, Immunoglobulin; PBMC, peripheral blood mononuclear cell; SLE, systemic lupus erythematosus.
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Received February 14, 2008. Revised March 18, 2008. Accepted March 31, 2008.
*These authors contributed equally to this work.
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