Association between endogenous expression of IFN-β-inducible genes in peripheral blood mononuclear cells with T-cell reactivity to myelin basic protein (MBP) and tetanus toxoid (TT) in untreated MS patients.

(a) In a previous study, 4 out of 17 patients responded to MBP with CD4+ T-cell proliferation ex vivo [21]. By DNA array analysis of gene expression [18], we found that 75 out of 3284 genes were more than 1.5-fold differentially expressed (p<0.01) in the 4 patients who had CD4+ T-cell reactivity to MBP as compared to the 13 patients who did not show CD4+ T-cell reactivity to MBP (differentially expressed genes are highlighted with bold letters). Data were obtained from the substudy-1 population and are given as ratio of the mean gene expression in both groups.
(b) We compared these results with data on IFN-β treatment-induced gene-expression levels in 23 patients from a recent study from our group [22]: 23 out of the 75 (31%) genes differentially expressed in patients with MBP-induced T-cell proliferation were induced at least 1.5-fold in patients treated with IFN-β (false discovery rate< 1% for all genes). Out of the remaining 3209 genes 171 (5.3%) were similarly induced after treatment with IFN-β (X2 = 84.64, df = 1, p<0.001).
(c) Data on TT reactivity were available from 12 patients from the sub-study 1 population [21]. Dividing the patients into two groups according to the level of TT reactivity (6 TT high responders vs. 6 TT low responders), we calculated the gene-expression ratio and identified 6 genes that were more than 1.5-fold differentially expressed (p<0.01; bold letters). (b) 4 out of these 6 genes were also significantly regulated by treatment with IFN-β, although only one of these genes was induced more than 1.5-fold.
Association between endogenous expression of IFN-β-inducible genes in peripheral blood mononuclear cells with T-cell reactivity to myelin basic protein (MBP) and tetanus toxoid (TT) in untreated MS patients.