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

Abstract

Immunoglubulin (Ig)M responses directed to oxida- tive 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 catabo lites (TRYCATs) were analyzed. IgM responses to OSEs, but not NO-adducts, were significantly reduced at the end of term. There we re 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 associat- ed 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 pos- itively associated. The attenuation of natural IgM-mediated re- sponses to OSEs at the end of term may indicate lowered activity of this part of the compensatory ( anti-)inflammatory reflex sys- tem and may be partly explained by lowered bacterial transloca- tion. Increased IgM responses to N O-cysteinyl is a biomarker of lifetime depression and may be in duced by bacterial transloca- tion. Natural IgM-mediated autoimmune responses, increased nitrosylation and higher CRP levels may have negative regulato- ry effects on the TRYCAT pathway.