Interferon-beta increases BAFF levels in multiple sclerosis: implications for B cell autoimmunity.

Abstract

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)-beta 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-beta-treated multiple sclerosis patients. Serum BAFF concentrations were determined by ELISA. This cross-sectional study involved 107 donors. IFN-beta therapy strongly induced BAFF transcription proportionally to the IFN-beta biomarker MxA in monocytes and granulocytes in vivo. BAFF serum concentrations were elevated in IFN-beta-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-beta 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-beta 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-beta 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-beta therapy, thus explaining interindividual differences of the therapeutic response.

• Authors: M Krumbholz, H Faber, F Steinmeyer, L-A Hoffmann, T Kümpfel, H Pellkofer, T Derfuss, C Ionescu, M Starck, C Hafner, R Hohlfeld, E Meinl
• Journal: Brain : a journal of neurology (Brain) Vol. 131 Issue Pt 6 Pg. 1455-63 (Jun 2008) ISSN: 1460-2156 [Electronic] England
• PMID: 18474519 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B-Cell Activating Factor
• B-Cell Activation Factor Receptor
• Tumor Necrosis Factor Ligand Superfamily Member 13
• Interferon-beta

Topics

• Adult
• Autoimmunity
• B-Cell Activating Factor (blood, metabolism)
• B-Cell Activation Factor Receptor (metabolism)
• B-Lymphocytes (drug effects, immunology)
• Case-Control Studies
• Cells, Cultured
• Cross-Sectional Studies
• Enzyme-Linked Immunosorbent Assay (methods)
• Female
• Humans
• Immunotherapy (methods)
• Interferon-beta (analysis, therapeutic use)
• Male
• Multiple Sclerosis (drug therapy, immunology)
• Tumor Necrosis Factor Ligand Superfamily Member 13 (metabolism)