Gut permeability and mimicry of the Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) as potential mechanisms related to a subgroup of people with schizophrenia with elevated antigliadin antibodies (AGA IgG)

Abstract

About one third of people with schizophrenia have elevated IgG antibodies to gliadin (AGA IgG) and increased inflammation. Understanding the mechanism by which this immune response occurs is critical to the development of personalized treatments. We examined gut permeability and mimicry to the glutamate receptor as possible mechanisms related to high gliadin antibodies (AGA IgG) seen in some people with schizophrenia. The Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) has a similar protein structure to gliadin representing a potential target for cross reactivity or mimicry. In a population of schizophrenia subjects (N = 160) and healthy controls (N = 80) we analyzed serum samples for both GRINA and Anti-Saccharomyces Cerevisiae antibodies (ASCA), related to gut permeability. Schizophrenia patients compared to controls had a higher prevalence of positivity to ASCA IgA (p = 0.004) and IgG (p < 0.001). Multinomial logistic regression showed an association between AGA IgG and ASCA IgG in schizophrenia (p = 0.05 for the estimated regression coefficient) but not in healthy controls (p = 0.13). GRINA IgG was higher in schizophrenia patients than in healthy controls (0.43 ± 0.30 vs. 0.22 ± 0.24, p < 0.001). Logistic regressions showed an association between AGA IgG and GRINA IgG in schizophrenia (p = 0.016 for the estimated regression coefficient) but not for the controls (p = 0.471). Thus, we propose that mimicry through the presence of cross-reactivity between gliadin and GRINA might disrupt the functions of the glutamate system and relate to illness pathophysiology in those with schizophrenia and elevated AGA IgG.