Krumbholz, M. and Faber, H. and Steinmeyer, F. and Hoffmann, L. -A. and Kuempfel, T. and Pellkofer, H. and Derfuss, T. and Ionescu, C. and Starck, M. and Hafner, C. and Hohlfeld, R. and Meinl, E. (2008) Interferon-beta increases BAFF levels in multiple sclerosis: implications for B cell autoimmunity. BRAIN, 131. pp. 1455-1463. ISSN 0006-8950, 1460-2156
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; LYMPHOCYTE STIMULATOR; ACTIVATING FACTOR; TNF FAMILY; NEUTRALIZING ANTIBODIES; NEUROMYELITIS-OPTICA; CEREBROSPINAL-FLUID; MYASTHENIA-GRAVIS; EPITHELIAL-CELLS; autoantibodies; B cells; interferon; multiple sclerosis therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Nov 2020 05:06 |
| Last Modified: | 02 Nov 2020 05:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30769 |
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