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

[Ecoclimber]

J Immunol. 2014 Jun 13. pii: 1400118. [Epub ahead of print]
Rituximab Efficiently Depletes Increased CD20-Expressing T Cells in Multiple Sclerosis Patients.
Palanichamy A1, Jahn S1, Nickles D1, Derstine M1, Abounasr A1, Hauser SL1, Baranzini SE1, Leppert D2, von Büdingen HC3.

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

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.

Permission to repost
thought it was interesting

"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

 

[anciendaze]

Just want to add that both Th17 and CD20 are still markers for a small part of a very general response. The significance of the effect of Rituximab is less as an immediate therapy than as a clue that some part of immune response is involved in maintaining a pathological state. In a few cases treatment with this drug can lead to remission of symptoms, but we don't actually know how this happens. The best results seem to occur if the pathology has not been established for a long time.

Until we know what is causing this pathological state, large-scale suppression of immune response is unwise. There is more than a little evidence that immune function is already compromised, and various microbes normally considered harmless are increased in number, without fingering a single pathogen as the culprit. This also turns up in "autoimmune" diseases. I think anyone with experience with, say MS or SLE, will warn that current treatment is often worse than mild disease.

Except for dealing with knuckleheads who are convinced that immune dysfunction is the result of thinking the wrong thoughts, (which they can talk you out of,) the Rituximab results are best seen as a lead for deeper research. This is one of several solid threads to pull, (drop in anaerobic threshold on 2-day CPET is another solid lead) and we just have to make sure that competent people actually follow them. If there were no history of deliberate delay and obfuscation, plus misfeasance, malfeasance and nonfeasance concerning research funds, this would be business as usual in biomedical research. Unfortunately, we still haven't rid ourselves of the effects of merging cohorts with even less well-defined problems via criteria that could mean anything a doctor deemed to be a patient's personal problem.

For critics: if there was no deliberate delay why did it take so long to study the physiology of exercise in patients who have been reporting very serious exercise intolerance, (on a par with, though different from, heart failure,) from day one? Private exploration of this avenue started in the 1980s. The equipment required is not terribly expensive. Anyone want to make a detailed accounting of how you did spend money specifically allocated for research on this illness?