RESUMEN
AIM: Patients with multiple sclerosis (MS) present with heterogeneous clinical courses. To elucidate whether different immunopathological mechanisms are involved in MS subgroups, we compared serum levels of TNF-α, IL-1ß, hs-CRP, receptor activator of nuclear factor kappa-B ligand (RANKL) and peripheral blood foxp3 expression in clinical subtypes of MS (relapsing remitting: RR-MS; secondary progressive: SP-MS; primary progressive: PP-MS) and healthy subjects. METHODS: In a case-control study, 72 healthy individuals and 72 age- and sex-matched multiple sclerotic patients (57% RR-MS, 18% SP- MS and 25% PP-MS) were evaluated. The age, gender distribution, and BMI of MS patients in these three sup-types were similar. The serum levels of TNF-α, IL-1ß, and RANKL were measured by ELISA. hs-CRP was measured by imunoturbidimetric method. Peripheral blood mononuclear cells expression of Foxp3 was measured by real time PCR. RESULTS: A significant elevation of TNF-α, hs-CRP, IL-1ß and RANKL and diminution of Foxp3 expression in MS patients compared to control was found (P<0.001). PP-MS had highest levels of TNF-α, IL-1ß, CRP and RANKL, and lowest levels of foxp3, with difference in TNF-α reached significant level (P<0.01). RANKL and TNF-α showed a reverse (P<0.01) significant correlation with Foxp3 relative expression levels. Patients with early age onset (onset before 30 years) had significantly higher levels of hs-CRP compared to late age onset patients. CONCLUSION: These data demonstrate the presence of immunopathogenesis differences between relapsing and non-relapsing form and is also the first to stress a role for cytokine RANKL in MS patients.