Sunday, 15 June 2014

Anti B cell treatment kills T cells. Throwing the cat amongst the pigeons

Palanichamy A, Jahn S, Nickles D, Derstine M, Abounasr A, Hauser SL, Baranzini SE, Leppert D, von B├╝dingen HC.Rituximab Efficiently Depletes Increased CD20-Expressing T Cells in Multiple Sclerosis Patients. J Immunol. 2014 Jun 13. pii: 1400118. [Epub ahead of print]


In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. Based on indirect evidence, it is generally believed that elimination of the Ag-presenting capabilities and Ag nonspecific immune functions of B cells underlie the therapeutic efficacy. However, a small subset of T lymphocytes (T cells) was shown to also express CD20, but controversy prevails surrounding the true existence of this T cell subpopulation. Using single-cell imaging flow cytometry and expression profiling of sorted lymphocyte subsets, we unequivocally demonstrate the existence of CD3+CD20dim T cells. We show that in MS patients, increased levels of CD3+CD20dim T cells are effectively depleted by RTX. The pathological relevance of this T cell subset in MS remains to be determined. However, given their potential proinflammatory functionality, depletion of CD20-expressing T cells may also contribute to the therapeutic effect of RTX and other mAbs targeting CD20

                                                A herring or a cat

We have spent years building up the T cell hypothesis in MS. every therapy was thrown at T cells, but then came along anti-CD20 for arthritis and then MS and hey we now have an anti-B cell treatment that treats MS. Time to throw away ideas and get new ones...but hey now it is reported that a small subset of T cells also express anti-CD20 and they are depleted. So it this a cop out or a red herring until we know what this subset does may be the former for the glass half full or the latter for the half empty. If this is the answer, then it should be possible to reduce side effects by targeting this small subset.

3 comments:

  1. Would alemtuzumab have an impact on these cells?

    ReplyDelete
  2. Hint:

    "Frequency of Th17 CD20+ cells in the peripheral blood of rheumatoid arthritis patients is higher compared to healthy subjects"

    http://arthritis-research.com/content/pdf/ar3541.pdf

    ReplyDelete

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