Will tickle your scientific bone here by bringing to light this interesting paper from the RA world
http://www.ncbi.nlm.nih.gov/pubmed/20547657
Rheumatology (Oxford). 2010 Oct;49(10):1911-9. doi: 10.1093/rheumatology/keq159. Epub 2010 Jun 14.
Epstein-Barr virus in bone marrow of rheumatoid arthritis patients predicts response to rituximab treatment.
Magnusson M, Brisslert M, Zendjanchi K, Lindh M, Bokarewa MI.
CONCLUSIONS: EBV and parvovirus genomes are frequently found in bone marrow of RA patients. The presence of EBV genome was associated with a better clinical response to RTX. Thus, presence of EBV genome may predict clinical response to RTX.
I am curious to hear your perspective as whether Rituximab in ME would have a etter response if there was EBV involvement and whether performing bone marrow biopsies could bring more information to the table in patients with ME, especially in the light of a Rituximab trial.
I think it is important not to get muddled about viruses in these diseases. And I am not accusing PR posters of being muddled, just the people writing papers. In order not to be too rude I will try and generalise. Papers that look at viruses in patients with autoimmunity nearly always give the impression that the virus is somehow explaining some part of the causation - often a 'trigger'. But when we look at the results it does not look as if they would explain anything to do with disease causation.
In the Magnusson paper all that is found is that RA patients with more EBV in bone marrow respond to a treatment better (we do not know if it is just this treatment or any treatment). We already know that more or less everyone has EBV in their B cells at a certain stage of maturation. So what the EBV findings here seem to be telling us is that patients who respond to a treatment better have more B cells at a particular stage of maturation in their bone marrow. That might tie in with Dr Bansal's work on B cell populations but it does not imply that EBV is causing anything. It might be true that people who respond better handle EBV differently but it is a big jump to saying that this helps cause the disease. On the contrary, it might be that if these people respond better to treatment they have milder disease.
The presence of EBV may facilitate the development of various autoimmune diseases but these bone marrow data would not seem to tell us anything about that. To my mind a lot of immunologists are still hidebound by the idea that autoimmunity arises from an interaction between genetic and environmental factors, with the environmental factor often thought of in terms of an infective 'trigger'. EBV infection occurs in infancy and in late teens and in neither group is there any suggestion of increased incidence of RA. In setting up a theoretical model for a disease one has to find one that predicts the right statistics for the epidemiology. The epidemiology of RA shows a genetic bias but is otherwise as far as we can see
random. (Except that smoking increases risk.) People feel they need another factor to explain who gets RA and when, but they do not seem to realise that it will have to be a random factor. In general viruses are either everywhere or pass from person to person in epidemics. Nobody has ever caught RA.
An extension of this gene/environmental trigger idea is almost universally believed in by immunologists but belongs to the stone age of the 1960s to my mind - something called molecular mimicry. The idea is that if you come across a foreign antigen that looks very like a self antigen you may get 'cross reactivity'. This idea was proposed for rheumatic fever and became accepted by everyone, despite there being no evidence. When rheumatic fever was cured by penicillin all the infectious disease physicians became 'immunologists' and brought their ideas with them. But it makes no sense. If a foreign protein is like a self protein you are less likely to respond to it. If cross reactivity was easy we would all have all sorts of autoimmune diseases. With the probably exception of post-infective polyneuropathy there is really zero evidence that it happens. What we do know happens is that a foreign protein can get involved in an autoimmune reaction to a quite unrelated molecule that it can bind to - like the coeliac case Andrew raised. But in most cases both the foreign and the self molecule are around all the time. The autoimmune reaction comes
at random out of the blue. The point of the vicious cycle model based on random immunoglobulin mutation is that it makes sense of this. The random nature of the immune response is normally completely invisible, because of clonal selection in response to presence of antigen but for antigens that are always available, like self ones, the sudden random appearance of a response does make sense.
I think viruses may well be more relevant to ME because ME is more likely to be quite a mix of different diseases and in some cases unusual ways of handling viruses might be very important. However, I do not think attempts to chase virus causes of RA are of much interest here. Even in ME I would personally want much firmer evidence for viral involvement before using anti-viral agents. There is a significant possibility that the 'trigger' illness that some people have, is not a trigger at all. If a form of immune dysregulation is set up that disturbs the control of messenger molecules involved in responses to viruses then the first sign of that may well be a disturbed, or amplified and prolonged, response to a virus - any old virus. We know from RA that autoimmune processes may set up years before they actually show themselves in terms of symptoms. An anamnestic boost to an autoimmune response from a non-specific infection is quite feasible as a reason for first symptoms, but the immune response itself would already have been there.
Also, a number of immunologists seem to think there is some mystery about the response to rituximab. People often say there is no correlation between level of B cell depletion and benefit. I have no idea who invented that idea - there is a very clear correlation. For some reason people want to find another explanation but since we predicted what would happen with rituximab in advance (and published it in Brit J. Rheumatology) I cannot quite see the need!
). This question in the light of findings such as this one in RA 
