I read through Karins thread and she tested positive for autoantibodies to the folate receptors through Quadroz and high supplementation helps her.
I've been thinking about antibodies and wondering if autoantibodies would occur mainly due to increased cell death. I say this because cell proteins are generally inside the cell and the ones outside the cell would be within the fatty membrane. And antibodies bind to substances in plasma. So high autoantibodies may mean there is increased cell death and the cell contents are spilling into the blood causing antibodies to bind to them. I''m guessing high folinic would still help b/c it would saturate the remaining cells that are not damaged.
I'd be interested in anyones thoughts (especially you Rich!)
GlobalPilot
Hi, GlobalPilot.
I think you are on the right track here. Cells normally die by apoptosis, which is an orderly process in which the contents of the cells are contained in membrane-bound bodies and are engulfed and digested by phagocytes such as macrophages. However, under disease conditions, cells also die by necrosis, in which the cell membrane is ruptured and the contents are released. I think that this latter process is more likely to lead to development of autoantibodies, because substances that are normally not exposed to the immune cells would be exposed in this case.
I don't know of studies of necrosis in ME/CFS. I do know that there have been two or three studies that have found elevated rates of apoptosis in ME/CFS. I also know that Dr. Howard at AcumenLab often finds elevated cell-free DNA in PWMEs/PWCs, which comes from cells that have died, and I also know that Howard Urnovitz and his company Chronix have reportedly found that cell-free DNA can be analyzed for complementary DNA sequences that are characteristic of retroviruses. Chronix has joined forces with the company that promotes Ampligen, and I understand that they are calling this "Next Generation Sequencing." Before the blow-up involving Judy Mikovits and the WPI, I think I heard that they were going to pursue this type of DNA sequencing to look for the retroviruses, but I don't know what the status of that is now.
Anyway, a possible scenario is that viral or retroviral infection causes cells to die prematurely (whether by apoptosis or necrosis, I don't know), and that this causes release of fragments of DNA and perhaps other intracellular substances to the blood plasma, and that this provokes formation of autoantibodies. Perhaps this accounts for the (I think, mild) elevation of autoantibodies in ME/CFS. These autoantibodies may help to promote inflammation by other parts of the immune system.
If this mechanism is valid, then perhaps the Rituximab treatment (in the cases in which it was successful) knocked out the B cells and thus the production of autoantibodies, and perhaps this then lowered the inflammation and the accompanying oxidative stress, allowing glutathione to recover and breaking the vicious circle involving the partial methylation cycle block, correcting the dysfunction in the sulfur metabolism and the Th2 immune shift, so that the people were able to recover.
Well, there are a lot of "what if's" in this little fairy tale, but you asked for my thoughts!
Best regards,
Rich