variation in nod2 augments th2- and th17 responses to myelin basic protein in multiple sclerosisnod2变化增强th2和th17反应髓磷脂碱性蛋白在多发性硬化症.pdfVIP

Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis 1 1 2 1 1 Chris Juul Hedegaard , Christian Enevold , Finn Sellebjerg , Klaus Bendtzen , Claus Henrik Nielsen * 1 Institute for Inflammation Research, Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet, Denmark, 2 Danish MS Research Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Denmark Abstract Variations in the gene for the nucleotide-binding oligomerisation domain (NOD) 2 have been associated with Crohn’s disease but not multiple sclerosis (MS). Here we investigate the effect of three polymorphisms in the NOD2 gene (rs5743277, rs2066842 and rs5743291) on cytokine production and CD4+ T cell proliferation elicited by human myelin basic protein (MBP) in blood mononuclear cell (MNC) cultures from 29 patients with MS. No polymorphism was observed at rs5743277. No associations with the rs2066842 polymorphism were found. Concerning rs5743291, none were homozygous for the minor allele. Seven of 29 (24%) patients were heterozygous, and five of these (71%) exhibited increased MBP-induced CD4+ T cell proliferation versus four of 22 (18%), who were homozygous for the major allele (p ,0.04). Interleukin (IL)-5 was induced by MBP in MNC from the same five carriers versus two (9%) homozygotes (p,0.004); four carriers (57%) versus three non-carriers (14%) exhibited IL-17 responses to MBP (p,0.04). By contrast, we found no association between the polymorphisms investigated and interferon-gamma-, tumor necrosis factor-alpha-, IL-2, -4- or IL-10 responses to MBP. These results indicate that the rs5743291 polymorphism inf