People with ME/CFS are also more likely to have genetic risk factors associated with autoimmunity and personal and/or family histories of autoimmune conditions. And, clinical trials have demonstrated early success with various immunomodulatory treatments in subsets of people with ME/CFS, including endoxan, rituximab, and immunoadsorption.
In a comparison of ME/CFS patients with 201 healthy controls, significant associations were seen with two specific autoimmunity-related risk alleles only in the ME/CFS patients who reported acute onset of disease with an infection but not in those with ME/CFS without infection-triggered onset or the controls.
In a 2020 paper, Scheibenbogen and pharmacologist Klaus Wirth presented a "unifying hypothesis" of ME/CFS pathophysiology based on the finding of elevations in autoantibodies against beta2-adrenergic receptors and muscarinic acetylcholine receptors in some individuals with the condition.
Rituximab: Work on infusions of the B-cell depleting agent has been conducted by Norwegian researchers beginning in 2011 with a small randomized trial and an open-label, phase 2 study in 2015, both showing clinical responses in ME/CFS. However, a subsequent phase 3, randomized clinical trial of 151 patients, again diagnosed using the Canadian criteria, was negative. There are several possible explanations for this, Scheibenbogen noted. For one, the maintenance dose had to be reduced because of a lack of financial support. "This was probably critical. The lower dose was insufficient to adequately deplete B cells."
I bolded the last part of that quote from Dr. Scheibenbogen because her statement is exactly what I have been saying for several years re: Phase 3 of the Rituximab Trial. And recently in a video, Drs. Fluge & Mella confirmed this (I wish I had the video to link here and will try to find it).
In Phase 3, they were forced to reduce the maintenance dose of Rituximab for all subjects in the trial due to financial reasons (so the dose was lower than the BSA formula for many subjects) meaning that it was not sufficient to fully deplete their B-cells. This does not mean that Rituximab is an effective treatment for ME/CFS but it means that Phase 3 of the trial did not produce accurate/valid results due to changing the dosing regime!
The rest of the article discusses other potential treatments including Cyclophosphamide, Immunoadsorption, and next-gen IgG-targeting therapies such as other monoclonal antibody treatments.
"Emerging evidence suggests that autoimmunity plays a role in postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and that targeting autoantibodies could be a promising treatment approach."
So far ... we have few and underfinanced clinical studies, but the good news is we have promising emerging treatment options,” Dr. Scheibenbogen said.
Dr. Komaroff said he views autoimmunity as a likely component of the ME/CFS spectrum, but not the only one. “My current view of this illness is that there’s a final common pathway in the brain that leads to the symptoms of the illness. But that final common pathway can be triggered by a variety of different things, one of which could be autoantibodies while another could be infection or inflammation in the brain.”
Komaroff said he views autoimmunity as a likely component of the ME/CFS spectrum, but not the only one. "My current view of this illness is that there's a final common pathway in the brain that leads to the symptoms of the illness. But that final common pathway can be triggered by a variety of different things, one of which could be autoantibodies while another could be infection or inflammation in the brain."