IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression
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.
KeywordsDepression 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.
No specific funding was obtained for this study.
All authors contributed equally to the work.
- Alonso Fernandez F (2001) Somatoform depressive disorders. An R Acad Nac Med (Madr) 118(4):745–766Google Scholar
- American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. Text Revision (DSM-IV-TR), WashingtonGoogle Scholar
- Burridge S (2011) Myristic acid. Linkage of this saturated fatty acid to a wide variety of proteins has a key role in processes such as protein membrane localization and ceramide biosynthesis. Lipid Maps—Nat Lipidomics Gatew. doi: 10.1038/lipidmaps.2011.3
- Cantor F (2010) Central and peripheral fatigue: exemplified by multiple sclerosis and myasthenia gravis. Phys Med Rehabil 2(5):399–405Google Scholar
- Joseph M, Nagaraj R (1997) Is the role of fatty acids only to provide membrane-anchor in fatty acylated proteins? Ind J Biochem Biophys 34(1–2):1–5Google Scholar
- Kerr JR, Petty R, Burke B, Gough J, Fear D, Sinclair LI, Mattey DL, Richards SC, Montgomery J, Baldwin DA, Kellam P, Harrison TJ, Griffin GE, Main J, Enlander D, Nutt DJ, Holgate ST (2008) Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Infect Dis 197(8):1171–1184PubMedCrossRefGoogle Scholar
- Maes M, Mihaylova I, Leunis JC (2007b) Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression. Neuro Endocrinol Lett 28(6):861–867PubMedGoogle Scholar
- Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2009a) Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett 30(4):470–476PubMedGoogle Scholar
- Maes M, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2011b) Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Sci Monitor 17(4):SC11–SC15Google Scholar
- Maes M, Twisk F, Kubera M, Ringel C (2012) Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increases in interleukin-1, tumor necrosis factor-α, neopterin, lysozyme and PMN-elastase. J Affect Disord 136(3):933–939PubMedCrossRefGoogle Scholar
- Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA (2003) Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett 335(3):151–154PubMedCrossRefGoogle Scholar
- Vernon SD, Whistler T, Cameron B, Hickie IB, Reeves WC, Lloyd A (2006) Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus. BMC Infect Dis 31:6–15Google Scholar
- Zameer A, Hoffman SA (2001) Immunoglobulin binding to brain autoimmune mice. J Neurobiol 120:10–18Google Scholar