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

Abstract

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.