title: BAFF is a biological response marker to IFN-beta treatment in multiple sclerosis.
abstract: Multiple sclerosis (MS) is a complex autoimmune disease characterized by the destruction of the myelin sheath of neurons. Interferon beta (IFN-beta) is currently the major drug used to treat MS. Some patients fail to respond to this treatment, in some cases due to the development of neutralizing antibodies (NAb) to IFN-beta. We used microarray analysis and RT-PCR to measure gene expression in whole blood, 9-15 h postinjection, in patients with and without NAbs to IFN-beta. The canonical marker of biological response to IFN-beta, myxovirus resistance protein A, was upregulated in all NAb- patients while remaining unchanged in NAb+ patients. Genes functioning in immune response pathways were dominant in the set of differentially expressed genes: 73 immune response genes were identified as upregulated and 29 genes were identified as downregulated. B-cell activating factor (BAFF) is a strong candidate marker for biological and clinical response as well as for predisposition to NAb development. We demonstrate that it is responsive to IFN-beta in vitro and in vivo, and that its soluble form is elevated in serum from NAb- but not NAb+ patients. We conclude BAFF is a good biomarker for IFN-beta response, and requires further studies to determine its value as a marker for clinical response and NAb predisposition.
authors: Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors: Kaushal S
authors: KS
authors: Gandhi
authors: Fiona C
authors: FC
authors: McKay
authors: Stephen D
authors: SD
authors: Schibeci
authors: Jonathan W
authors: JW
authors: Arthur
authors: Rob N
authors: RN
authors: Heard
authors: Graeme J
authors: GJ
authors: Stewart
authors: David R
authors: DR
authors: Booth
mesh_terms: D000917:Antibody Formation / Q000235:genetics; D053264:B-Cell Activating Factor / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D020869:Gene Expression Profiling; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; C505719:TNFSF13B protein, human; D016899:Interferon-beta