TY - JOUR
T1 - Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia
AU - Severance, Emily G.
AU - Gressitt, Kristin L.
AU - Halling, Meredith
AU - Stallings, Cassie R.
AU - Origoni, Andrea E.
AU - Vaughan, Crystal
AU - Khushalani, Sunil
AU - Alaedini, Armin
AU - Dupont, Didier
AU - Dickerson, Faith B.
AU - Yolken, Robert H.
N1 - Funding Information:
This work was supported by a NIMH P50 Silvio O. Conte Center at Johns Hopkins (grant# MH-94268); by the Brain and Behavior Research Foundation (formerly NARSAD) where Dr. Severance is a Scott-Gentle Foundation Young Investigator; and by the Stanley Medical Research Institute. These funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - (10 max): neuroinflammation
KW - Bipolar disorder
KW - Diet
KW - Food sensitivity
KW - Gliadin
KW - Psychosis
KW - Schizoaffective disorder
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U2 - 10.1016/j.nbd.2012.07.005
DO - 10.1016/j.nbd.2012.07.005
M3 - Article
C2 - 22801085
AN - SCOPUS:84864928219
SN - 0969-9961
VL - 48
SP - 447
EP - 453
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -