Metabolic Brain Disease

, Volume 27, Issue 4, pp 415–423 | Cite as

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

  • Michael Maes
  • Ivana Mihaylova
  • Marta Kubera
  • Jean-Claude Leunis
  • Frank N. M. Twisk
  • Michel Geffard
Research Paper


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 




Conflicts of interest

The authors do not report any conflicts of interest.

Funding source

No specific funding was obtained for this study.


All authors contributed equally to the work.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Michael Maes
    • 1
  • Ivana Mihaylova
    • 2
  • Marta Kubera
    • 3
  • Jean-Claude Leunis
    • 4
  • Frank N. M. Twisk
    • 5
  • Michel Geffard
    • 6
  1. 1.Maes Clinics @ TRIA, Piyavate HospitalBangkokThailand
  2. 2.CRC-MHAntwerpBelgium
  3. 3.Department of Experimental Endocrinology, Institute of PharmacologyPolish Academy of SciencesKrakówPoland
  4. 4.Laboratoire AtegisWavreBelgium
  5. 5.Me-de-patienten FoundationLimmenthe Netherlands
  6. 6.Association Institute for Research & Development in Human Pathology and TherapyTalenceFrance

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