title: 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.
authors.affiliation: Maes Clinics @ TRIA, Piyavate Hospital, 998 Rimklongsamsen Road, Bangkok, 10310, Thailand. dr.michaelmaes@hotmail.com
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.forename: Ivana
authors.initials: I
authors.lastname: Mihaylova
authors.forename: Marta
authors.initials: M
authors.lastname: Kubera
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Leunis
authors.forename: Frank N M
authors.initials: FN
authors.lastname: Twisk
authors.forename: Michel
authors.initials: M
authors.lastname: Geffard
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D000704:Analysis of Variance; D001327:Autoimmune Diseases / Q000276:immunology* / Q000523:psychology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D003865:Major Depressive Disorder / Q000276:immunology* / Q000523:psychology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D015673:Fatigue Syndrome, Chronic / Q000276:immunology* / Q000523:psychology; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D019814:Myristic Acid / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000939:Epitopes; D007075:Immunoglobulin M; D019814:Myristic Acid; D019308:Palmitic Acid; D009569:Nitric Oxide; D010649:Phenylalanine; C057785:S-farnesylcysteine; D003545:Cysteine