Please bear with me. The RituxMe trial is on my mind lately. If Rituximab is confirmed to be an effective treatment, what could the disease mechanism look like? Plausibly it could involve autoantibodies that keep the body in "sickness mode" without the kind of tissue damage that's normally involved in autoimmune disease. That could mean antibodies that interfere with various chemical signals in the body, so that cells would be receiving distorted messages. There are signals for all sorts of things. There would be a lot of dysregulation with seemingly no cause. That might sound like the kind of problem certain psychiatrists like to talk about in the context of psychosomatic illness but it must be more than that since ignoring these warning signals is actually harmful. Dr Naviaux thinks that we are in a coordinated state of hypometabolism of the kind seen in worms that are subjected to harsh environmental conditions. This so-called Dauer state involves purinergic signalling, which is handled by an evolutionary ancient network of receptors and signals. Some preliminary evidence suggests that the drug suramin can bring cells out of this hypometabolic state by blocking the P2X receptors, and that there is something in the blood of patients that causes this metabolic dysfunction. This something could be an antibody. Antibodies are produced by plasma cells which are a type of older B cells. Rituximab presumably works in ME/CFS by eliminating B cells so that the pool of antibody producing B cells is not replenished and autoantibody concentrations eventually drop. What keeps the B cells going though? One model is that the antibodies result in a signal that tells the B cells to keep producing these antibodies. It turns out that B cells have several types of P2X receptors. So if these B cells produce antibodies that result in P2X receptors activation, and if P2X receptors activation is the sort of signal that tells B cells to keep producing antibodies, we would have a nice autoimmune loop. It also turns out that lots of things have P2X receptors so these signals could be affecting a lot of things. Do the details line up? I don't know yet. I'm also wondering about PEM and whether natural cell death related to exertion (possibly occurring at higher rates due to hypometabolism) could cause a delayed increase in the kind of signals (ATP acting on P2X receptors) involved here, but that's an even wilder guess.