Chemokines and their receptors are important in the trafficking of peripheral leukocytes into the central nervous system, a major event in the pathogenesis of multiple sderosis (MS). Evidence based on clinical, pathological and magnetic resonance imaging grounds supports some divergence between forms of MS with relapses [relapsing-remitting (RR) and secondary progressive (SP)] and the primary progressive (PP) form. To elucidate whether different pathogenic mechanisms are involved in PPMS, we compared membrane expression of a group of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood of 68 MS patients (25 PPMS, 23 SPMS and 20 RRMS) and 26 healthy controls. We found a significant increase in surface expression of CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients compared to controls. Increased levels of CXCL10 (IP-10) and CCL5 (RANTES) in cerebrospinal fluid were also observed in a subgroup of MS patients. These results support that chemokines and their receptors are involved in the pathogenesis of MS However, a pattem of chemokine-chemokine receptor expression characteristic of each clinical form of the disease failed to be observed.
Whether autoreactive T cells from multiple sclerosis (MS) patients display a certain autoreactive pattern is controversial. In this study, we have analyzed reactivity towards myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), alpha B-crystallin and S100beta antigens in 35 relapsing-remitting MS patients and 12 healthy controls (HC). During relapse, we observed T-specific proliferation towards MBP (15.8%), MOG (38.9%), alpha B-crystallin (11.1%) and S100beta (26.3%) in MS patients. Reactivity to MBP (12%), MOG (28%), alpha B-crystallin (28%) and S100beta (19.2%) was also observed in HC. There were changes in the specific proliferation in consecutive samples obtained from either patients or HC. Such fluctuations did not follow any specific or conservative patterns. Antigen-specific cytokine production was also assessed as a method to evaluate whether there were differences in the qualitative response between MS patients and HC, with negative results. In summary, we show here that the reactivity patterns, as measured by specific proliferation and cytokine production, are similar in RR-MS patients and HC and fluctuate over time.
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