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, 998 Rimklongsamsen Road, Bangkok, 10310, Thailand, .
Metabolic Brain Disease (Impact Factor: 2.64). 05/2012; 27(4). DOI: 10.1007/s11011-012-9316-8
Source: PubMed


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.

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Available from: Frank N.M. Twisk, Mar 19, 2015
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    ABSTRACT: Introduction: The World Health Organization has classified myalgic encephalomyelitis (ME) as a neurological disease since 1969 considering chronic fatigue syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with "chronic fatigue syndrome." Areas covered: The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME. These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus. Expert opinion: Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this "chronic fatigue spectrum" should, therefore, use the above-mentioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.
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