Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia

Emily G Severance, Kristin L. Gressitt, Meredith Halling, Cassie R. Stallings, Andrea E. Origoni, Crystal Vaughan, Sunil Khushalani, Armin Alaedini, Didier Dupont, Faith B. Dickerson, Robert H Yolken

Research output: Contribution to journalArticle

Abstract

Immune system factors including complement pathway activation are increasingly linked to the etiology and pathophysiology of schizophrenia. Complement protein, C1q, binds to and helps to clear immune complexes composed of immunoglobulins coupled to antigens. The antigenic stimuli for C1q activation in schizophrenia are not known. Food sensitivities characterized by elevated IgG antibodies to bovine milk caseins and wheat glutens have been reported in individuals with schizophrenia. Here, we examined the extent to which these food products might comprise the antigen component of complement C1q immune complexes in individuals with recent onset schizophrenia (n = 38), non-recent onset schizophrenia (n = 61) and non-psychiatric controls (n = 63). C1q seropositivity was significantly associated with both schizophrenia groups (recent onset, odds ratio (OR) = 8.02, p ≤ 0.008; non-recent onset, OR = 3.15, p ≤ 0.03) compared to controls (logistic regression models corrected for age, sex, race and smoking status). Casein- and/or gluten-IgG binding to C1q was significantly elevated in the non-recent onset group compared to controls (OR = 4.36, p ≤ 0.01). Significant amounts of C1q-casein/gluten-related immune complexes and C1q correlations with a marker for gastrointestinal inflammation in non-recent onset schizophrenia suggests a heightened rate of food antigens in the systemic circulation, perhaps via a disease-associated altered intestinal permeability. In individuals who are in the early stages of disease onset, C1q activation may reflect the formation of immune complexes with non-casein- or non-gluten-related antigens, the presence of C1q autoantibodies, and/or a dissociated state of immune complex components. In conclusion, complement activation may be a useful biomarker to diagnose schizophrenia early during the course of the disease. Future prospective studies should evaluate the impacts of casein- and gluten-free diets on C1q activation in schizophrenia.

Original languageEnglish (US)
Pages (from-to)447-453
Number of pages7
JournalNeurobiology of Disease
Volume48
Issue number3
DOIs
StatePublished - Dec 2012

Fingerprint

Complement C1q
Glutens
Caseins
Antigen-Antibody Complex
Triticum
Schizophrenia
Milk
Antigens
Complement Activation
Odds Ratio
Food
Immunoglobulin G
Logistic Models
Gluten-Free Diet
Immunologic Factors
Autoantibodies
Immunoglobulins
Immune System
Permeability
Complement System Proteins

Keywords

  • (10 max): neuroinflammation
  • Bipolar disorder
  • Diet
  • Food sensitivity
  • Gliadin
  • Psychosis
  • Schizoaffective disorder

ASJC Scopus subject areas

  • Neurology

Cite this

Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia. / Severance, Emily G; Gressitt, Kristin L.; Halling, Meredith; Stallings, Cassie R.; Origoni, Andrea E.; Vaughan, Crystal; Khushalani, Sunil; Alaedini, Armin; Dupont, Didier; Dickerson, Faith B.; Yolken, Robert H.

In: Neurobiology of Disease, Vol. 48, No. 3, 12.2012, p. 447-453.

Research output: Contribution to journalArticle

Severance, EG, Gressitt, KL, Halling, M, Stallings, CR, Origoni, AE, Vaughan, C, Khushalani, S, Alaedini, A, Dupont, D, Dickerson, FB & Yolken, RH 2012, 'Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia', Neurobiology of Disease, vol. 48, no. 3, pp. 447-453. https://doi.org/10.1016/j.nbd.2012.07.005
Severance, Emily G ; Gressitt, Kristin L. ; Halling, Meredith ; Stallings, Cassie R. ; Origoni, Andrea E. ; Vaughan, Crystal ; Khushalani, Sunil ; Alaedini, Armin ; Dupont, Didier ; Dickerson, Faith B. ; Yolken, Robert H. / Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia. In: Neurobiology of Disease. 2012 ; Vol. 48, No. 3. pp. 447-453.
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