engleski

CD95 expression on peripheral blood in T lymphocytes in patients with relapsing-remitting, primary and secondary progressive multiple sclerosis

CD95-mediated apoptosis is a potent endogenous pathwy of T lymphocyte elimination that has been suggested to be altered in multiple sclerosis (MS). The aim of the study was to analyze the expression od CD95 molecule on peripheral blood CD4+ and CD8+ T lymphocytes in patients with relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS), and secondary progressive multiple sclerosis (SPMS). The analysis was performed immediately before and after pulse corticosteroid therapy (consisting of intravenous methylprednisone 1000 mg/day in 250 ml saline in short infusions over five days), and six months after the beginning of investigation, when RRMS patients were in remission. The prospective study included 50 patients with multiple sclerosis diagnosed by McDonald's criteria:27 patients with RRMS(4 M, 23 F) aged 20-51, median 37 years ; 10 patientswith PPMS (5 M, 5 F) aged 24-57, median 39.5 years ; and 13 patients with SPMS (4 M, 9 F) aged 30-53, median 42 years. Disease duration ranged from 3 months to 17 years, median 2 years in RRMS group ; from 1.5 to 14 years, median 4 years in PPMS group ; and from 3 to 26 years, median 11 years in SPMS group. The mean EDSS scale was 3.24&#177; 1.18 in RRMS, 5&#177; 1.55 in PPMS, and 5.62&#177; 1.24 in SPMS patients. The proportion of CD95+T lymphocyte subsets was analyzed by use of monoclonal antibodies (anti-CD4-PE/Cy5, anti-CD8-FITC and anti-CD95-PE, DAKO) and flow cytometry (FACScan cytometer and CellQuest software, Becton Dickinson). Results were presented as mean &#177; standard deviation. On statistical analysis, two-way ANOVA for repeated measures with post hoc Sheffe's test was used. The values of p<0.05 were considered statistically significant. The proportion of CD4+CD95+ T lymphocytes significantly decreased after therapy in RRMS (46.91&#177; 7.79 vs. 39.5&#177; 5.67, p<0.01), PPMS (46.16&#177; 5.9 vs. 40.01&#177; 7.22, p<0.01) and SPMS patients (51.26&#177; 6.56 vs. 44.68&#177; 7.75, p<0.01). After six months, their proportion significantly increased in PPMS (40.02&#177; 7.22 vs. 46.1&#177; 5.95, p<0.01) and SPMS patients (44.68&#177; 7.75 vs. 50.99&#177; 6.46, p<0.01), whereas in RRMS patients it showed further significant decrease (39.5&#177; 5.67 vs. 36.1&#177; 4.62, p<0.01). The proportion of CD8+CD95+ T lymphocytes also decreased in all three groups of patients after therapy, being significantly only in RRMS (26.71&#177; 5.21 vs. 18.89&#177; 5.05, p<0.01) and SPMS patients (21.25CD95-mediated apoptosis is a potent endogenous pathwy of T lymphocyte elimination that has been suggested to be altered in multiple sclerosis (MS). The aim of the study was to analyze the expression od CD95 molecule on peripheral blood CD4+ and CD8+ T lymphocytes in patients with relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS), and secondary progressive multiple sclerosis (SPMS). The analysis was performed immediately before and after pulse corticosteroid therapy (consisting of intravenous methylprednisone 1000 mg/day in 250 ml saline in short infusions over five days), and six months after the beginning of investigation, when RRMS patients were in remission. The prospective study included 50 patients with multiple sclerosis diagnosed by McDonald's criteria: 27 patients with RRMS(4 M, 23 F) aged 20-51, median 37 years ; 10 patientswith PPMS (5 M, 5 F) aged 24-57, median 39.5 years ; and 13 patients with SPMS (4 M, 9 F) aged 30-53, median 42 years. Disease duration ranged from 3 months to 17 years, median 2 years in RRMS group ; from 1.5 to 14 years, median 4 years in PPMS group ; and from 3 to 26 years, median 11 years in SPMS group. The mean EDSS scale was 3.24&#177; 1.18 in RRMS, 5&#177; 1.55 in PPMS, and 5.62&#177; 1.24 in SPMS patients. The proportion of CD95+T lymphocyte subsets was analyzed by use of monoclonal antibodies (anti-CD4-PE/Cy5, anti-CD8-FITC and anti-CD95-PE, DAKO) and flow cytometry (FACScan cytometer and CellQuest software, Becton Dickinson). Results were presented as mean &#177; standard deviation. On statistical analysis, two-way ANOVA for repeated measures with post hoc Sheffe's test was used. The values of p<0.05 were considered statistically significant. The proportion of CD4+CD95+ T lymphocytes significantly decreased after therapy in RRMS (46.91&#177; 7.79 vs. 39.5&#177; 5.67, p<0.01), PPMS (46.16&#177; 5.9 vs. 40.01&#177; 7.22, p<0.01) and SPMS patients (51.26&#177; 6.56 vs. 44.68&#177; 7.75, p<0.01). After six months, their proportion significantly increased in PPMS (40.02&#177; 7.22 vs. 46.1&#177; 5.95, p<0.01) and SPMS patients (44.68&#177; 7.75 vs. 50.99&#177; 6.46, p<0.01), whereas in RRMS patients it showed further significant decrease (39.5&#177; 5.67 vs. 36.1&#177; 4.62, p<0.01). The proportion of CD8+CD95+ T lymphocytes also decreased in all three groups of patients after therapy, being significantly only in RRMS (26.71&#177; ; 5.21 vs. 18.89&#177; ; 5.05, p<0.01) and SPMS patients (21.25&#177; 4.35 vs. 17.17&#177; 5.83, p<0.05). After six months, their proportion increased in patients with the progressive form of the disease, being significant only in SPMS patients (17.17&#177; 5.83 vs. 21.21&#177; 4.59, p<0.05), and decreased in RRMS patietns, however, not reaching statistical significance. Thus, differences in the dynamics of these laboratory parameters, indicators of T lymphocyte apoptosis, point to different pathophysiological eventsin RRMS patients compared to PPMS and SPMS patients.

CD95; apoptosis; multiple sclerosis

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