title: An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS.
abstract: BACKGROUND
  It has been shown that chronic fatigue syndrome (CFS) and major depression (MDD) are accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS and MDD are accompanied by an IgM-mediated immune response directed against nitro-serum bovine albumin (BSA), which is a neoepitope of BSA formed by damage caused by nitrosative stress.
  
  
  OBJECTIVE
  Toward this end, we examined serum IgM antibodies to nitro-BSA in 13 patients with CFS, 14 subjects with partial CFS, 16 patients with MDD and 11 normal controls.
  
  
  RESULTS
  We found that the prevalence and mean values for the serum IgM levels directed against nitro-BSA were significantly greater in patients with partial CFS, CFS and MDD than in normal controls, and significantly greater in CFS than in those with partial CFS and MDD. We found significant and positive correlations between serum IgM levels directed against nitro-BSA and symptoms of the FibroFatigue scale, i.e. aches and pain and muscular tension. There was also a strong positive correlation between serum IgM titers directed against nitro-BSA and an index of increased gut permeability ("leaky gut"), i.e. serum IgM and IgA directed against LPS of different gram-negative enterobacteria.
  
  
  CONCLUSIONS
  The abovementioned results indicate that both CFS and MDD are accompanied by a) an increased gut permeability which has allowed an exaggerated passage of BSA through a compromised epithelial barrier; b) increased nitrosative stress which has induced damage to BSA; and c) an IgM-mediated immune response which is directed against the nitro-BSA neoepitopes. Nitrosative stress is one of the factors underpinning the comorbidity and clinical overlap between CFS and MDD.
authors.affiliation: MCare4U Outpatient Clinics, Antwerp, Belgium. crc.mh@telenet.be
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
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015824:Blood-Air Barrier / Q000502:physiology; D003865:Major Depressive Disorder / Q000150:complications / Q000276:immunology* / Q000523:psychology; D015673:Fatigue Syndrome, Chronic / Q000150:complications / Q000276:immunology* / Q000523:psychology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000627:therapeutic use; D007075:Immunoglobulin M / Q000276:immunology*; D007413:Intestinal Mucosa / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009603:Nitroso Compounds / Q000276:immunology*; D010539:Permeability; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000276:immunology*
chemical_list: D007070:Immunoglobulin A; D007075:Immunoglobulin M; D009603:Nitroso Compounds; D026361:Reactive Nitrogen Species; C091665:S-nitrosoalbumin; D012710:Serum Albumin, Bovine