IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major  depression.

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and depression are considered to be neuro-immune disorders (Maes and Twisk, BMC Medicine 8:35,  2010). There is also evidence that depression and ME/CFS are accompanied by  oxidative and nitrosative stress (O&NS) and by increased autoantibodies to a  number of self-epitopes some of which have become immunogenic due to damage by  O&NS. The aim of this study is to examine IgM-mediated autoimmune responses to  different self-epitopes in ME/CFS versus depression. We examined serum IgM  antibodies to three anchorage molecules (palmitic and myristic acid and  S-farnesyl-L-cysteine); acetylcholine; and conjugated NO-modified adducts in 26  patients with major depression; 16 patients with ME/CFS, 15 with chronic fatigue;  and 17 normal controls. Severity of fatigue and physio-somatic (F&S) symptoms was  measured with the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale. Serum  IgM antibodies to the three anchorage molecules and NO-phenylalanine were  significantly higher in ME/CFS than in depression. The autoimmune responses to  oxidatively, but not nitrosatively, modified self-epitopes were significantly  higher in ME/CFS than in depression and were associated with F&S symptoms. The  autoimmune activity directed against conjugated acetylcholine did not differ  significantly between ME/CFS and depression, but was greater in the patients than  controls. Partially overlapping pathways, i.e. increased IgM antibodies to a  multitude of neo-epitopes, underpin both ME/CFS and depression, while greater  autoimmune responses directed against anchorage molecules and oxidatively  modified neo-epitopes discriminate patients with ME/CFS from those with  depression. These autoimmune responses directed against neoantigenic determinants  may play a role in the dysregulation of key cellular functions in both disorders,  e.g. intracellular signal transduction, cellular differentiation and apoptosis,  but their impact may be more important in ME/CFS than in depression.