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Well, the continued existence the CAR-T cells would be responsible for the continued B cell depletion to some degree. It is not clear quite what determines B cell return after deep depletion. They remain absent quite long after therapeutic levels of rituximab are present, for instance...

I don't see plasmablasts as having much role - they are just a transient state in blood. I presume the antibodies continue to go down because splenic plasma cells are dying off and not being replaced while there are no B cells.

It is interesting that almost nobody came back to the thread and expressed enthusiasm about Unrest as an educational tool. I see that I said nothing. I saw an excerpt at the Houses of Parliament and then joined a panel at a full screening a few days later. I left that very uncertain that Unrest...

The Wikipedia entry on pragmatic trials is informative. It is also intriguing to see that in this sort of case entries are always written by people who like the idea. Those who don't cannot be bothered with pointing out the poor logic. A pragmatic trial is one that in some way forfeits the...

The pragmatic trials unit at Queen Mary says: What is a Pragmatic Clinical Trial? Schwartz and Lellouch were the first to use the word “pragmatic” in relation to clinical trials in 1967. They defined a pragmatic trial as a trial designed to help chose between care options, as opposed to an...

Looking at the author list this looks pretty much like a scam advert.

I am not aware of mesenchymal stem cells being of any value in inflammatory or autoimmune disease. Is there any evidence? Autologous stem cells have been used as rescue following immunoablation for autoimmune disease but that doesn't mean the stem cells are treating the disease - just stopping...

The other point is that the blood text mentions randomised trials, and as we saw with PACE, randomisation isn't actually what makes a trial bulletproof. Adequate controlling is far more important and can quite often be achieved without randomising. Pragmatic trials are more or less by definition...

I haven't looked at the paper beyond the abstract but this sounds like special pleading, as you say. There is a very simple solution to the problem. Stop using causal language at all. A trial should be reported and readers should be able to conclude what they like about cause and effect. When I...

Maybe it's TGFbeta after all. It was the one cytokine to actually show up in some studies. It is a mediator of repair and tissue strengthening. It is a potent modulator of T cell function. It gets invisibly painted on to tissue matrix so that tissues can 'remember' how to respond over long...

There is something about Nath's comments that reminds me of Fiona Watt at the MRC 'How awfully shocking that you should be disappointed in our research. After all we are THE MOST IMPORTANT PEOPLE in this science game and we do all this entirely out of our desire to help you poor people.' Pah!

We targeted the B cells in RA because we have worked out all the steps in the mechanism, including why B cells are specifically suited to colonise joint synovium in a chronic inflammatory situation, why joint synovial is susceptible to small immune complex mediated inflammation, why rheumatoid...

That was what we tried to do with combinations early on but soon realised that we did not have the tools to break through. I have been trying to persuade people to take this approach for twenty years now but almost nobody seems to get the rationale - they just think of killing B cells without...

Yes, but quite a lot is known about signals from infection and exercise that will impinge on the brain - through hypothalamus mostly. The brain loop idea would be that the response is set wrong. We don't know much that would help explain how that would work but we know that it can happen for...

Cytokine assays, at least up until I retired in 2010, found little or no value in clinical medicine because they are extraordinarily poor at telling you what is going on even when there is barn door pathology. In RA the cytokines are going berserk in joints and liver. You can tell that because...

It will be interesting to see what is found but I am sceptical about him finding anything very much. Generally speaking if blood brain barrier is altered enough to allow white cells in you either rapidly become comatose or, if it is local, appear to have had a stroke or similar similar. MRI...

My experience is that this myth has largely been generated in the last 50 years. My parents were medical and we had friends with MS. I was told about MS probably at the age of about 11. Nobody suggested that there was any psychiatrisation. It was known that there was gross brain pathology. A...

This is all pretty well understood. Rituximab will produce profound B lymphocytopenia at quite small doses. We went down to a single dose of 500mg and still got total blood depletion. I am sure you can go lower. But the point of killing B cells is not to kill B cells themselves, since they...

What we may get is not so much a biomarker as a biological clue - maybe from genetic studies. But once we have a biological clue, whether or not it marks a process directly, I think the game will change overnight. I also think that the explanation may become clear very rapidly. I don't think...

I suspect that ideas of loops within brains are not so popular with a number of members because in a sense they imply that ME/CFS is indeed a 'functional neurological disorder' if we take that to mean a disorder driven by disturbed regulation in the brain without any structural pathological...