Preprint Article Version 2 This version is not peer-reviewed

In Schizophrenia, Low Natural IgM Antibody Titers to Oxidative Specific Epitopes and Higher IgM Responses to Nitrated and Nitrosylated Proteins Strongly Predict Negative Symptoms, Neurocognitive Impairments and the Deficit Syndrome

Version 1 : Received: 4 October 2018 / Approved: 4 October 2018 / Online: 4 October 2018 (15:18:40 CEST)
Version 2 : Received: 6 October 2018 / Approved: 8 October 2018 / Online: 8 October 2018 (13:51:40 CEST)

How to cite: Maes, M.; Kanchanatawan, B.; Sirivichayakul, S..; Carvalho, A.F. In Schizophrenia, Low Natural IgM Antibody Titers to Oxidative Specific Epitopes and Higher IgM Responses to Nitrated and Nitrosylated Proteins Strongly Predict Negative Symptoms, Neurocognitive Impairments and the Deficit Syndrome. Preprints 2018, 2018100083 (doi: 10.20944/preprints201810.0083.v2). Maes, M.; Kanchanatawan, B.; Sirivichayakul, S..; Carvalho, A.F. In Schizophrenia, Low Natural IgM Antibody Titers to Oxidative Specific Epitopes and Higher IgM Responses to Nitrated and Nitrosylated Proteins Strongly Predict Negative Symptoms, Neurocognitive Impairments and the Deficit Syndrome. Preprints 2018, 2018100083 (doi: 10.20944/preprints201810.0083.v2).

Abstract

Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in natural regulatory autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative specific epitopes (OSEs), nitroso (NO) and nitro (NO2) adducts in schizophrenia remain unknown.This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl and NO2-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls.Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO2-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2 – 42.2 %) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO2-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall.These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in lowered IgM responses to MDA and azelaic acid (part of the CIRS) attenuate the negative immune-regulatory feedback on the primary immune response and that this process may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.

Subject Areas

immune, inflammation, natural IgM autoimmune, oxidative stress, kynurenine, schizophrenia, psychosis

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