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Role of IL-17-producing lymphocytes in severity of multiple sclerosis upon natalizumab treatment

Authors

  • U. Bühler
  • V. Fleischer
  • F. Luessi
  • A. Rezk
  • P. Belikan
  • C. Graetz
  • R. Gollan
  • C. Wolf
  • J. Lutz
  • A. Bar-Or
  • V. Siffrin
  • F. Zipp

Journal

  • Multiple Sclerosis Journal

Citation

  • Mult Scler J 23 (4): 567-576

Abstract

  • Objective: Natalizumab is known to prevent T-helper cells entering the central nervous system (CNS). We hypothesize that more pathogenic T-helper cells are present outside the CNS and a possible relationship to disease severity. Methods: Characterization and enrichment of human CD4+IL-17+ cells were performed ex vivo using peripheral blood mononuclear cells from natalizumab-treated relapsing-remitting multiple sclerosis (RRMS) patients (n = 33), untreated RRMS patients (n = 13), and healthy controls (n = 33). Magnetic resonance imaging (MRI) scans were performed routinely for patients. Results: Lymphocytes were elevated in peripheral blood of natalizumab-treated patients compared to untreated patients and healthy controls. Whereas group comparison for CD4+IL-17+ numbers also differed, CD4+IFN-{gamma}+ and CD4+IL-22+ counts were not increased. CD4+IL-17+ cells not only expressed but also secreted IL-17. In natalizumab-treated patients, IL-17+ cell frequency was found to correlate with T1-hypointense lesions, but was not an indicator for rebound activity after treatment discontinuation, except in one patient who experienced a fulminant rebound, and interestingly, in whom the highest IL-17+ cell levels were observed. Conclusion: Increased lymphocytes and CD4+IL-17+ cells in the blood of RRMS patients receiving natalizumab corroborate the drug's mechanism of action, that is, blocking transmigration to CNS. Correlation between IL-17-expressing lymphocytes and T1-hypointense lesions underlines the important role of these cells in the disease pathology.


DOI

doi:10.1177/1352458516658559