Antigliadin Antibodies (AGA IgG) Are Related to Neurochemistry in Schizophrenia

Abstract

Inflammation may play a role in schizophrenia; however, subgroups with immune regulation dysfunction may serve as distinct illness phenotypes with potential different treatment and prevention strategies. Emerging data show that about 30% of people with schizophrenia have elevated antigliadin antibodies of the IgG type, representing a possible subgroup of schizophrenia patients with immune involvement. Also, recent data have shown a high correlation of IgG-mediated antibodies between the periphery and cerebral spinal fluid in schizophrenia but not healthy controls, particularly AGA IgG suggesting that these antibodies may be crossing the blood-brain barrier with resulting neuroinflammation. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that allows the quantification of certain neurochemicals in vivo that may proxy inflammation in the brain such as myoinositol and choline-containing compounds (glycerophosphorylcholine and phosphorylcholine). The objective of this exploratory study was to examine the relationship between serum AGA IgG levels and MRS neurochemical levels. We hypothesized that higher AGA IgG levels would be associated with higher levels of myoinositol and choline-containing compounds (glycerophosphorylcholine plus phosphorylcholine; GPC + PC) in the anterior cingulate cortex. Thirty-three participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder had blood drawn and underwent neuroimaging using MRS within 9 months. We found that 10/33 (30%) had positive AGA IgG (≥20 U) similar to previous findings. While there were no significant differences in myoinositol and GPC + PC levels between patients with and without AGA IgG positivity, there were significant relationships between both myoinositol (r = 0.475, p = 0.007) and GPC + PC (r = 0.36, p = 0.045) with AGA IgG levels. This study shows a possible connection of AGA IgG antibodies to putative brain inflammation as measured by MRS in schizophrenia.

Keywords: GPC + PC; antibody; gliadin; gluten; inflammation; myoinositol; neuroimaging; schizophrenia.

Figure 1

Voxel images and a representative spectrum (black line), LCModel fit (red line), residual (black line at top). Myoinositol (mI), Phosphocreatine+Creatine (tCr), Phosphorylcholine+Glycerophosphorylcholine (tCho), Glutamate (Glu), and N-Acetylaspartate (tNAA).

Figure 2

Correlation plot showing a strong positive relationship (r = 0.48, p = 0.007) between AGA IgG and myoinositol levels. 31/33 of the participants had data available.

Figure 3

Correlation plot showing a positive relationship (r = 0.36, p = 0.045) between AGA IgG and GPC + PC levels. 31/33 of the participants had data available.