Monday, 25 July 2016

Th17 important in MS

Bühler U, Fleischer V, Luessi F, Rezk A, Belikan P, Graetz C, Gollan R, Wolf C, Lutz J, Bar-Or A, Siffrin V, Zipp F. Role of IL-17-producing lymphocytes in severity of multiple sclerosis upon natalizumab treatment. Mult Scler. 2016 . pii: 1352458516658559. [Epub ahead of print]

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


  1. Does th17 interface with B cells , the remarkable suppression for anti-CD20s is something that cannot be ignored !

  2. eat tonne of cinnamon @ get rid of Th17's

    I read everywhere that MS is a CNS disease and all its activity is confined on the other side of the BBB, all this locally synthesed OCB stuff, etc etc
    Soo they suggest this is a systematic process?

    1. And I eat "kilos" of cinnamon every day, but because I think delicious, but so 40 tablespoons you can die from eating cinnamon...

      At least I think it's pretty obvious that there is an interaction between T and B Lymphocytes, and they act together, if only it were of T lymphocytes action would see so many people "cured" of MS only using Interferons, and isn't what we see in practice: NABs putting down the Interferons ...

    2. Still can't get how they see peripheral changes when dealing with CNS-restricted process

    3. Peripheral process enters CNS and affects process

  3. What is the link between RAB32 and IL-17 or TH-17?

    1. Maybe alot probably very little. The question is what causes the problem that leads to rab32 and mam being induced. Many say Th17 in some eae models maybe I'm MS in not so sure.


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