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Hello,
I read somewhere from Cort Johnson that Dr. Dan Peterson had found specific biomarkers that indicated which subset of patients would respond to rituximab. Does anyone know what these biomarkers/levels are?
Thank you,
JB
Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors. Autoantibodies against G-protein coupled receptors were shown to play a pathogenic role in several autoimmune diseases. Here, serum samples from a patient cohort from Berlin (n=268) and from Bergen with pre- and post-treatment samples from 25 patients treated within the KTS-2 rituximab trial were analysed for IgG against human α and β adrenergic, muscarinic (M) 1-5 acetylcholine, dopamine, serotonin, angiotensin, and endothelin receptors by ELISA and compared to a healthy control cohort (n=108). Antibodies against β2, M3 and M4 receptors were significantly elevated in CFS patients compared to controls. In contrast, levels of antibodies against α adrenergic, dopamine, serotonin, angiotensin, and endothelin receptors were not different between patients and controls. A high correlation was found between levels of autoantibodies and elevated IgG1-3 subclasses, but not with IgG4. Further patients with high β2 antibodies had significantly more frequently activated HLA-DR+ T cells and more frequently thyreoperoxidase and anti-nuclear antibodies. In patients receiving rituximab maintenance treatment achieving prolonged B-cell depletion, elevated β2 and M4 receptor autoantibodies significantly declined in clinical responder, but not in non-responder. We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and β adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy. The association of autoantibodies with immune markers suggests that they activate B and T cells expressing β adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.
I think this may be what you're looking for:
https://www.ncbi.nlm.nih.gov/pubmed/26399744
I'm not.I am unclear why the CMRC wants to ignore all the UK expertise and set up non-population based cohorts from clinic lists.
I read somewhere from Cort Johnson that Dr. Dan Peterson had found specific biomarkers that indicated which subset of patients would respond to rituximab. Does anyone know what these biomarkers/levels are?
In patients receiving rituximab maintenance treatment achieving prolonged B-cell depletion, elevated β2 and M4 receptor autoantibodies significantly declined in clinical responder, but not in non-responder.
https://www.ncbi.nlm.nih.gov/pubmed/26399744
The above statement seems to suggest the reason some ME/CFS patients do not respond to rituximab is not because those non-responders have some non-autoimmune subtype of ME/CFS, but because for some reason, the rituximab did not work for these patients, and was not able to reduce the patients' production of autoantibodies.
In other words, even in the rituximab non-responders, their ME/CFS may still be autoimmune in nature.
That is not to say that the β2 and M4 autoantibodies are the cause of ME/CFS; ME/CFS may be caused by some other autoantibodies in the blood; but if rituximab is doing its job, it will reduce the level of all autoantibodies, so measuring the reduction in the β2 and M4 autoantibodies is just a gauge of whether rituximab is working.
@Jonathan Edwards, am I on the right lines here?
If the rituximab non-responders are indeed patients in which rituximab has failed to curb their autoimmunity, is there anything further that can be done in such cases? If these patients still have their ME/CFS caused by autoimmunity, can the autoimmunity be tackled in other ways if rituximab fails?
And do we know why rituximab fails to reduce levels of autoantibodies in some patients?
One possibility we have considered is that the problem, at least for responders, is the presence of antibodies that are not auto- but are causing trouble for some other reason. If they are antibodies made by short lived plasma cells then there may be a response.
@Jonathan Edwards, that is intriguing, could you give some relevant examples of this?