title: Cytokine profile, Foxp3 and nuclear factor-kB ligand levels in multiple sclerosis subtypes.
abstract: OBJECTIVE
  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-1β, 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-1β, 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-1β 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-1β, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Alatab
authors.forename: Z
authors.initials: Z
authors.lastname: Maghbooli
authors.forename: A
authors.initials: A
authors.lastname: Hossein-Nezhad
authors.forename: M
authors.initials: M
authors.lastname: Khosrofar
authors.forename: F
authors.initials: F
authors.lastname: Mokhtari
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000276:immunology; D053245:RANK Ligand / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein