Immunoadsorption to remove β2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME

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 beta 2 adrenergic receptors, and muscarinic 3 and 4 acetylcholine receptors in a subset of patients. lmmunoadsorption (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 beta 2 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 beta 2 IgG antibodies rapidly decreased during IA in 9 of 10 patients. Also 6 months later beta 2 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 beta 2 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.