Abstract Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a condition characterised by extreme fatigue, memory impairment, pain and other symptoms that vary from patient to patient. It affects about 0.9% of the population and is often triggered by an acute viral or bacterial infection, such as Epstein-Barr virus. The underlying physiological and molecular basis of ME/CFS is unknown, and no effective treatments exist. One proposed mechanism is that the blood flow is altered by autoantibodies against receptors involved in blood flow regulation. Antibodies are generated by the immune system to recognise intruders and under normal conditions, our immune system is trained not to attack our own tissues. However, during a severe infection, the immune system adopts an "all hands on deck" approach, which results in some of the newly-produced antibodies escaping quality control and targeting our own tissues, autoantibodies. Receptors regulation blood flow are located in walls of blood vessels and cause a blood vessel to dilate or contract as the demand for oxygen and nutrients to tissues such as the brain or muscles changes. Research has found increased levels of these autoantibodies in ME/CFS patients and initial trials removing these autoantibodies from the blood using a technique called immunoadsorption have shown improvement in symptoms. In this project, we will test the hypothesis that autoantibodies can activate or inhibit the receptors responsible for the blood flow regulation, in a similar way medical drugs are used to regulate blood pressure. We aim to profile serum samples from 325 ME/CFS patients and 130 healthy individuals to determine the presence of autoantibodies against all thirty receptors involved in blood pressure regulation. Importantly, we will study the ability of autoantibodies detected in each sample to activate or inhibit these receptors in order to test the hypothesis that the activity of these autoantibodies is a decisive factor in the disease. If our hypothesis is correct, we will be able to develop an accurate blood test that may be able to detect ME/CFS earlier or to independently confirm the diagnosis. Ultimately, we hope that these results may also indicate a possible route for therapeutic intervention to counteract the effects of autoantibodies and alleviate the ME/CFS symptoms using a combination of already existing drugs, specific for each individual case. https://gtr.ukri.org/projects?ref=MR/Y003667/1
I think studying blood pressure regulation is a good idea, but I can't judge whether autoantibodies is the right hypothesis. All considered this looks interesting.
The above description of the project is lay summary. The technical summary is below. Aren't these Celltrend antibodies that don't differ between patients and controls?
I also think studying blood regulation seems like a very useful approach and I think there should also be some novel ideas to try to understand whether autoimmunity plays a part in ME/CFS, but I don't think that every research that somehow looks at autoimmunity should be focused solely on GPCR-AABs (especially when there's already many projects on this currently running). Between Scheibenbogen's research continuously showing that they don't seem to play much of a role, other groups work seemingly showing the same and Rituximab not working even though it should lower these aabs, I'd like projects that are focused on this to at least explore other avenues as well, so that one doesn't end up completely empty handed when 10+ projects on this yield null results. At least one can say that with the abundance of projects that are currently running on GPCR-AABs one will have final answers in the next year or two on their role in ME/CFS. Still seems likely that the conclusion could be "well we should have known this all along, there was never any evidence they played a role". I wonder why so many researchers are focused on them even though all evidence shows they don't seem to play any role. Have they all run out of ideas how to study the diseases meaningfully? To me it seems like many avenues are still completely unexplored, or at least the replication on previous results to confirm what roles these play could be trivially easy (for example why not do a couple of Doppler flow experiments when your research is focused on blood flow to see if van Campen/ Vissers results hold up?)...
It seems a long shot, but it's good that they are not just looking at antibody binding but also at whether or not the binding affects the activity of the receptors they bind. Via @Sid They don't lack ambition.
Just originality maybe. But at least it makes some sense for someone to try to replicate the negative findings from Berlin and show that they really are negative!
