Metabolic Brain Disease

, Volume 27, Issue 4, pp 415–423

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


    • Maes Clinics @ TRIA, Piyavate Hospital
  • Ivana Mihaylova
    • CRC-MH
  • Marta Kubera
    • Department of Experimental Endocrinology, Institute of PharmacologyPolish Academy of Sciences
  • Jean-Claude Leunis
    • Laboratoire Ategis
  • Frank N. M. Twisk
    • Me-de-patienten Foundation
  • Michel Geffard
    • Association Institute for Research & Development in Human Pathology and Therapy
Research Paper

DOI: 10.1007/s11011-012-9316-8

Cite this article as:
Maes, M., Mihaylova, I., Kubera, M. et al. Metab Brain Dis (2012) 27: 415. doi:10.1007/s11011-012-9316-8


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.


Depression Chronic fatigue syndrome Physio-somatic symptoms Oxidative and nitrosative stress Inflammation Cytokines Autoimmunity

Copyright information

© Springer Science+Business Media, LLC 2012