IgM-mediated autoimmune responses to oxidative specific epitopes, but not nitrosylated adducts, are significantly decreased in pregnancy: association with bacterial translocation, perinatal and lifetime major depression and the tryptophan catabolite (TRYCAT) pathway

Metab Brain Dis. 2017 Oct;32(5):1571-1583. doi: 10.1007/s11011-017-0040-2. Epub 2017 Jun 9.

Abstract

Immunoglubulin (Ig)M responses directed to oxidative specific epitopes (OSEs) and nitric oxide (NO)-adducts are significantly associated with major depression and physio-somatic symptoms. End of term serum IgM responses to OSEs and NO-adducts were assayed in pregnant women with (n = 24) and without prenatal depression (n = 25) as well as in 24 non-pregnant women. Associations of IgM/IgA responses to Gram-negative gut commensal bacteria (leaky gut index) and IgA/IgM responses to tryptophan catabolites (TRYCATs) were analyzed. IgM responses to OSEs, but not NO-adducts, were significantly reduced at the end of term. There were no significant associations between IgM responses to OSEs and perinatal depression, whilst IgM responses to NO-adducts, especially NO-cysteinyl, were significantly associated with a lifetime major depression. IgM responses to OSEs and NO-cysteinyl were significantly associated with IgA/IgM responses to Gram-negative bacteria, especially Morganella morganii, Klebsiella pneumoniae and Citrobacter koseri. IgM responses to NO-adducts and OSEs, especially malondialdehyde and myristic acid, and C-reactive protein (CRP) were inversely associated with TRYCAT pathway activity, whilst a lifetime depression and Pseudomonas putida were positively associated. The attenuation of natural IgM-mediated responses to OSEs at the end of term may indicate lowered activity of this part of the compensatory (anti-)inflammatory reflex system and may be partly explained by lowered bacterial translocation. Increased IgM responses to NO-cysteinyl is a biomarker of lifetime depression and may be induced by bacterial translocation. Natural IgM-mediated autoimmune responses, increased nitrosylation and higher CRP levels may have negative regulatory effects on the TRYCAT pathway.

Keywords: Compensatory (anti-)inflammatory reflex system (CIRS); Cytokines; Depression; Immune; Inflammation; Kynurenine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoimmunity / immunology*
  • Bacterial Translocation / immunology*
  • Biomarkers
  • Cytokines / metabolism
  • Depression, Postpartum / immunology
  • Depression, Postpartum / psychology
  • Depressive Disorder, Major / epidemiology
  • Depressive Disorder, Major / immunology*
  • Depressive Disorder, Major / psychology
  • Epitopes / immunology*
  • Female
  • Gram-Negative Bacteria / immunology
  • Humans
  • Immunoglobulin M / immunology*
  • Inflammation / immunology
  • Kynurenine / metabolism
  • Metabolic Networks and Pathways
  • Nitric Oxide / metabolism
  • Pregnancy / immunology*
  • Tryptophan / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Epitopes
  • Immunoglobulin M
  • Nitric Oxide
  • Kynurenine
  • Tryptophan