Multiple sclerosis: expression of C D1a and production of IL-12 p70 and IFN-γ by blood mononuclear cells in patients on combination therapy with IFN-β and glatiramer acetate compared to monotherapy with IFN-β

Abstract

Current therapy of multiple sclerosis (MS) with interferon-beta (IFN-b) or glatiramer acetate (GA) has modest effects on the course of MS. Both compounds affect several immune variables, like expression of cell surface molecules and cytokine levels. Here we compared untreated MS, therapy with IFN-b alone and combined with GA, and healthy controls (HC), regarding expression on HLA -DR⁺ blood mononuclear cells (MNC) of C D1a that is a cell surface molecule with capacity to present glycolipids to T cells, and of C D80 and C D86 which are costimulatory molecules that activate Th1 and Th2 responses. C ytokine production by MNC was also measured. Flow cytometry and ELISA were used. C ross-sectional comparisons revealed that untreated MS patients had higher C D1a⁺ HLA -DR⁺ MNC and lower IL-10 production compared to patients treated with IFN-b or IFN-b+G A or HC. Untreated MS patients also had higher spontaneous IFN-g and IL-12p70 production compared to MS patients treated with IFN-b+G A or HC, but not when compared to MS patients on monotherapy with IFN-b. Low C D1a⁺ HLA -DR⁺ MNC and low spontaneous production of IL-12p70 and IFN-g were more pronounced in patients treated with IFN-b+G A than with IFN-b alone. In order to clarify whether these changes reflect disease activity or treatment effects, we performed a follow up study. Nineteen MS patients with disease progression, despite monotherapy with IFN-b for more than one year, were re-examined after one to three and four to six months of treatment with IFN-b+G A. This combination therapy was associated with normalization of C D1a⁺ HLA -DR⁺ MNC, IL-12p70 and IFN-g. It remains to be shown whether these immunological changes imply a clinical benefit. Follow up studies of immune variables versus clinical effects during combined therapy of MS with IFN-b+G A are ongoing.

Keywords

C D1a glatiramer acetate IFN-β IFN-γ IL-12p70 multiple sclerosis

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