Format

Send to

Choose Destination
Brain Behav Immun. 2016 Feb;52:32-39. doi: 10.1016/j.bbi.2015.09.013. Epub 2015 Sep 21.

Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome.

Author information

1
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany. Electronic address: madlen.loebel@charite.de.
2
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.
3
CellTrend GmbH, Luckenwalde, Brandenburg, Germany.
4
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany; Labor Berlin GmbH, Immunology Department, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.
5
Department of Nephrology, Charité University Medicine Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Germany.
6
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Germany.
7
Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
8
Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.

Abstract

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.

KEYWORDS:

Autoantibodies; Chronic Fatigue Syndrome; GPCR; Rituximab

PMID:
26399744
DOI:
10.1016/j.bbi.2015.09.013
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center