title: IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology.
abstract: BACKGROUND
  There is evidence that depression is accompanied by oxidative and nitrosative stress (O&NS), as indicated by increased free radical levels, lipid peroxidation, and lowered antioxidant levels. The aims of the present study are to examine whether depression is accompanied by autoimmune responses directed against a) neoepitopes that are formed following O&NS damage; and b) the major anchorage molecules, i.e. palmitic and myristic acids and S-farnesyl-L-cysteine.
  
  
  METHODS
  We examined serum IgM antibodies to the conjugated fatty acids, palmitic and myristic acids; acetylcholine; S-farnesyl-L-cysteine; and NO-modified adducts in 26 depressed patients and 17 normal controls. Severity of depression was measured with the Hamilton Depression Rating Scale and severity of fatigue and somatic (F&S) symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.
  
  
  RESULTS
  The prevalences and mean values for the serum IgM levels directed against conjugated palmitic and myristic acids, acetylcholine, S-farnesyl-L-cysteine; and the conjugated NO adducts, NO-tyrosine, NO-phenylalanine, NO-aspartate, NO-histidine, and NO-creatine were significantly higher in depressed patients than in normal controls. The autoimmune responses were significantly related to FF symptoms, such as fatigue and a flu-like malaise, whereas the indicants of nitrosative stress were related to gastro-intestinal and autonomic symptoms.
  
  
  CONCLUSIONS
  Depression is characterized by IgM-related autoimmune responses directed against a) neoepitopes that are normally not detected by the immune system but that due to damage by O&NS have become immunogenic; and b) anchorage epitopes, i.e. palmitic and myristic acids, and S-farnesyl-L-cysteine. These autoimmune responses play a role in the inflammatory and O&NS pathophysiology of depression and may mediate the cellular dysfunctions that contribute to neuroprogression, e.g. aberrations in signal transduction, cellular differentiation and apoptosis.
authors.affiliation: Maes Clinics @ TRIA, Bangkok, 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: Michel
authors.initials: M
authors.lastname: Geffard
mesh_terms: D000109:Acetylcholine / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D016022:Case-Control Studies; D003545:Cysteine / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D004249:DNA Damage; D003863:Depression / Q000276:immunology*; D003866:Depressive Disorder / Q000150:complications / Q000276:immunology; D000939:Epitopes; D005221:Fatigue / Q000097:blood / Q000150:complications / Q000276:immunology; D005227:Fatty Acids / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D015227:Lipid Peroxidation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019814:Myristic Acid / Q000276:immunology / Q000378:metabolism; D017008:Negotiating; D009569:Nitric Oxide; D018384:Oxidative Stress / Q000276:immunology / Q000502:physiology; D019308:Palmitic Acid / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D000939:Epitopes; D005227:Fatty Acids; D007075:Immunoglobulin M; D019814:Myristic Acid; D019308:Palmitic Acid; D009569:Nitric Oxide; C057785:S-farnesylcysteine; D003545:Cysteine; D000109:Acetylcholine