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-γ+ 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
MS is caused by Th17 cells becuase this now dogma. So when we give natalizumab there are more CD4, IL-17 cells in the blood and the numbers correlate with T1-hypointense lesion.Therefore this validates the value of Th17 in disease pathogenesis.
However, proof is really getting rid of CD4+, IL-17+ T cells and it having an impact on MS.
However, so far depletion of CD4 T cells did not have a marked impact on MS lesions (although depletion levels were correlated relapse) and interleukin 17 neutralising antibodies reduced gadolinium lesions by about 50%. This gets the Th17ers mouths watering but remember beta interferon is much more effective than that and so many things do much better.
We need to be cautious until this action is shown