Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME

PLoS One. 2018 Mar 15;13(3):e0193672. doi: 10.1371/journal.pone.0193672. eCollection 2018.


Introduction: Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) point to an autoimmune disease directed against neurotransmitter receptors. We had observed elevated autoantibodies against ß2 adrenergic receptors, and muscarinic 3 and 4 acetylcholine receptors in a subset of patients. Immunoadsorption (IA) was shown to be effective in removing autoantibodies and improve outcome in various autoimmune diseases.

Methods: 10 patients with post-infectious CFS/ME and elevated ß2 autoantibodies were treated with IA with an IgG-binding column for 5 days. We assessed severity of symptoms as outcome parameter by disease specific scores. Antibodies were determined by ELISA and B cell phenotype by flow cytometry.

Results: IgG levels dropped to median 0.73 g/l (normal 7-16 g/l) after the 4th cycle of IA, while IgA and IgM levels remained unchanged. Similarly, elevated ß2 IgG antibodies rapidly decreased during IA in 9 of 10 patients. Also 6 months later ß2 autoantibodies were significantly lower compared to pretreatment. Frequency of memory B cells significantly decreased and frequency of plasma cells increased after the 4th IA cycle. A rapid improvement of symptoms was reported by 7 patients during the IA. 3 of these patients had long lasting moderate to marked improvement for 6-12+ months, 2 patients had short improvement only and 2 patients improved for several months following initial worsening.

Conclusions: IA can remove autoantibodies against ß2 adrenergic receptor and lead to clinical improvement. B cell phenotyping provides evidence for an effect of IA on memory B cell development. Data from our pilot trial warrants further studies in CFS/ME.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Adult
  • Autoantibodies / metabolism*
  • B-Lymphocytes
  • Blood Component Removal / instrumentation
  • Blood Component Removal / methods*
  • Fatigue Syndrome, Chronic / immunology
  • Fatigue Syndrome, Chronic / microbiology
  • Fatigue Syndrome, Chronic / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptides / administration & dosage*
  • Peptides / immunology
  • Receptor, Muscarinic M3 / immunology
  • Receptor, Muscarinic M4 / immunology
  • Receptors, Adrenergic, beta-2 / immunology*
  • Treatment Outcome


  • ADRB2 protein, human
  • Autoantibodies
  • Peptides
  • Receptor, Muscarinic M3
  • Receptor, Muscarinic M4
  • Receptors, Adrenergic, beta-2

Grant support

This trial was supported with a grant by Fresenius Medical Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CellTrend GmbH provided support in the form of measurement of autoantibodies and salary for author HH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.