Differential antibody responses to gliadin-derived indigestible peptides in patients with schizophrenia

Gluten consumption has previously been implicated in the development of schizophrenia, while an immunological link between gluten and schizophrenia was established by the detection of circulating antibodies against gliadin, a major component of wheat gluten. Several studies have reported an increase in circulating antibodies against native gliadin molecules that are unlikely to survive degradation in the digestive system. In this study, therefore, we measured plasma IgG and IgA antibodies against indigestible gliadin-derived peptide antigens using an in-house enzyme-linked immunosorbent assay (ELISA) among 169 patients with schizophrenia and 236 control subjects. We also examined plasma levels of IgG and IgA antibodies against the mixture of native gliadins using commercially available ELISA kits. The results showed that patients with schizophrenia had increased levels of plasma IgG against the γ-gliadin derived fragment, namely AAQ6C, but decreased levels of plasma IgG against α- and γ3-gliadin derived antigens, as compared with control subjects. This study also demonstrated a uniform decrease in plasma IgA antibodies against gliadin-derived antigens. There was no significant difference in the levels of plasma antibodies against native gliadins between the patient group and the control group. Of 8 gliadin-derived antigens tested, 4 showed a sensitivity of >20% against the specificity of ≥95% for detection of their corresponding antibodies in plasma. These 4 tests may thus have a potential to serve as biomarkers for identification of schizophrenia subgroups that may need an alternative therapy or precision treatment. Further investigation with clinical trials should be carried out to explore this possibility.