- β adrenergic and muscarinic acetylcholine receptor autoantibodies are elevated in a subset of patients with Chronic Fatigue Syndrome (CFS).
- Elevated autoantibodies in CFS correlate with elevated IgG1-3 subclass levels, thyreoperoxidase and ANA antibodies and T cell activation.
- In CFS patients responding to rituximab treatment, elevated antibody levels detected pre-treatment normalized in the majority of clinical responders post-treatment.
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 ß 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 ß2, 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 ß2 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 ß2 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 ß 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 ß adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.
Antibodies to ß adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome, by M Loebel, P Grabowski, H Heidecke, S Bauer, LG Hanitsch, K Wittke, C Meisel, P Reinke, HD Volk HD, Ø Fluge, O Mella, C Scheibenbogen, in Brain Behav Immun. 2015 Sep 20. pii: S0889-1591(15)30020-9. [Epub ahead of print]
New study sheds more light on why some people with ME/CFS may respond to rituximab, in ME Association News blog, 26 September 2015