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 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.

Natural regulatory IgM‐mediated autoimmune responses directed against malondialdehyde regulate oxidative and nitrosative pathways and coupled with IgM responses to nitroso adducts attenuate depressive and physiosomatic symptoms at the end of term pregnancy

“…In pregnancy, IgM responses to OSE, including MDA, are lowered at the end of term, and therefore lowered regulatory effects may be present. Increased levels of oxidative and nitrosative stress (O&NS), especially increased protein oxidation (as measured with advanced oxidation protein products) and nitric oxide (NO) production (as measured with NO metabolites) are strongly associated with prenatal depressive and physiosomatic symptoms (DPSS; including fatigue, pain, dyspepsia, and gastrointestinal symptoms) . Therefore, we may hypothesize that lowered IgM‐responses to MDA could play a role in the increased O&NS responses and DPSS.…”

“…Moreover, when NO (nitroso) binds to proteins, neoantigens are formed and some of these are immunogenic thereby triggering IgM responses to NO adducts . Major depression is accompanied by increased IgM responses to nitroso (NO) adducts …”

“…Increased levels of oxidative and nitrosative stress (O&NS), especially increased protein oxidation (as measured with advanced oxidation protein products) and nitric oxide (NO) production (as measured with NO metabolites) are strongly associated with prenatal depressive and physiosomatic symptoms (DPSS; including fatigue, pain, dyspepsia, and gastrointestinal symptoms). 20,21 Therefore, we may hypothesize that lowered IgMresponses to MDA could play a role in the increased O&NS responses and DPSS. However, there are no data available on possible associations between IgM responses to MDA and increased O&NS and DPSS at the end of term.…”

“…29 Major depression is accompanied by increased IgM responses to nitroso (NO) adducts. 16,20,30 Another consequence of elevated iNOS and NO production is peroxynitrite formation, which may lead to increased nitration of proteins, and NO 2 tyrosine formation. 31 NO 2 tyrosine levels are increased in depression and bipolar disorder.…”

A new schizophrenia model: immune activation is associated with induction of the tryptophan catabolite pathway and increased eotaxin levels which together determine memory impairments and schizophrenia symptom dimensions

“…The least detectable dose was 1.82 pg/mL for eotaxin, 1.58 pg/mL for MIP-1, 5.98 pg/mL for IL-1RA and 0.4 pg/mL for IL-10. "The 6 TRYCATs were assayed as described before [26,27]. Briefly, TRYCATs were dissolved in 200 μL dimethylsulfoxide (DMSO) (Acros).…”