122. High Antigliadin Antibodies (IgG) are Linked to Peripheral and Central Measures of Inflammation in a Subset of People With Schizophrenia

Abstract

Background: The pathophysiology of schizophrenia, or a subgroup of persons with schizophrenia, may be related to abnormal immune system function. Increased permeability of the mucosal epithelial tight junctions in the intestine and brain may contribute to possible inflammation in the periphery and CNS. Prior studies have shown that high levels of antibodies to gluten-related proteins, in particular, gliadin (AGA-IgG) are found in a subgroup of schizophrenia patients (~31%). Infiltration of inflammatory cytokines or microglial activation from antibody penetration into the brain may relate to psychiatric symptoms in this subgroup. Methods: We completed two pilot studies which examined (1) peripheral and (2) central measures that serve as indicators of inflammation in people with schizophrenia to AGA IgG. The first study examined cytokines TNF-α, IL-Iβ and AGA IgG (N = 100) using an automated enzyme-linked immunosorbent assay (ELISA) method with kits from Phadia AB. In the second study the relationship between proton magnetic resonance spectroscopy (MRS) data and AGA IgG values using native gliadin kits for ELISA from INOVA (N = 31) was examined. Spectra were acquired from the anterior cingulate using phase rotation STEAM: TR/TM/TE = 2000/10/6.5-ms, NEX = 128, water reference (NEX = 16) on a 3T Siemens Tim Trio. MRS data focused on choline (marker of cellular membrane turnover), and myoinositol (glial marker). Results: In the first pilot project, mean values of the two cytokines were twofold higher in people with schizophrenia who are positive to AGA IgG (P < .05). There were positive correlations between the AGA IgG antibodies and both log transformed TNF-α (r = .44, P < .0001) and IL-Iβ (r = .53, P < .0001), suggesting a robust association of AGA IgG antibodies with peripheral proinflammatory markers. The second pilot showed that individuals who were AGA IgG positive had a trend toward higher myoinositol as compared to those who were IgG negative (7.22 ± 0.70 vs. 6.68 ± 0.76 vs. (t = 1.67, P = .19). Also, there were significant correlations between myoinositol (r = .475, P = .007) and total choline levels (r = .36, P = .045) with AGA IgG, suggesting increased cellular membrane turnover and glial density with increasing AGA IgG. Conclusion: These data show a relationship between AGA IgG levels and inflammation in people with schizophrenia suggesting both brain and peripheral involvement. The results suggest the existence of a subset of people with schizophrenia with elevated AGA IgG (~31%) who may have a different etiology, which could lead to more personalized treatment.