A new German study published in Brain, Behavior, and Immunity by Loebel, et al. has found that Chronic Fatigue Syndrome* may be an infection-triggered autoimmune disease, at least in a subset of patients studied.

Samples from a large cohort (n=268) in Berlin and a smaller sample of patients treated with Rituximab (n=25) were measured against controls (n=168). Researchers found that antibodies against a neurotransmitter receptor were elevated in 29.5% of patients. Specifically, antibodies to ß2 adrenergic and M3 and M4 muscarinic cholinergic receptors, which are both G protein-coupled receptors (GCPRs).

Serum IgG against GCPRs were measured using an ELISA test.

In patients receiving Rituximab, those who were responders had significantly lower levels of ß2 and M4 autoantibodies after treatment. The authors suggest that these autoantibodies could be biomarkers to those CFS patients most likely to respond to Rituximab treatment.

This work extends previous research by Fluge, et al. which showed that 60% of CFS patients in their study achieved partial or full remission on Rituximab, which depletes CD20+ B cells, a component of the immune system. There are many different types of B cells. That it took five months for patients to see effects suggested to these researchers that it wasn’t directly the depletion of B cells causing the clinical effect, but rather the wiping out of memory B cells and the autoantibodies they were presumed to be creating against some unidentified target. With this new paper, Loebel, et al. believe they may have found that target.

Recent studies have found autoantibodies to ß1 and ß2 adrenergic receptors in Postural Orthostatic Tachycardia (POTS). ß adrenergic and muscarinic autoantibodies have been described in other autoimmune and neurological diseases. In addition to POTS, ß adrenergic autoantibodies have been found in orthostatic hypotension, dialated cardiomyopathy and Chagas disease, Muscarinic autoantibodies have been found in Myasthenia gravis, Sjorgen’s and schizophrenia. Both have been found in Graves’ disease.

The authors note that their finding of autoantibodies to ß2, M3, and M4 receptors does not exclude that additional autoantibodies not included in this study could also be at play.

*The term Chronic Fatigue Syndrome is used here as that is the term the study’s authors use. Patients were selected using the Canadian Consensus Criteria.