Abstract
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 immunoglobulin G (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 the 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 the increased levels of plasma IgG against the γ-gliadin-derived fragment, namely AAQ6C, but decreased levels of plasma IgG against the 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 eight gliadin-derived antigens tested, four showed a sensitivity of >20% against the specificity of ⩾95% for detection of their corresponding antibodies in plasma. These four tests may thus have a potential to serve as biomarkers for the 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.
Highlights
Schizophrenia is a complex psychiatric disorder, demonstrating heterogeneity in clinical presentation with a combination of positive, negative and cognitive symptoms.[1]
Multivariate linear regression analysis revealed a significant correlation between anti-gliadin antibodies (AGAs) immunoglobulin G (IgG) levels and against gliadin-derived antigen (AGDA) IgG levels (Supplementary Tables 9 and 10), in which anti-AL1G1 IgG level was the best predictor of AGA IgG level out of all AGDA IgG antibodies tested in the control group (Standardized β = 0.20, P = 0.004), while anti-AAQ6C IgG level was the most significantly correlated to AGA IgG levels in the patient group (Standardized β = 0.17, P = 0.037)
The levels of plasma IgG against γ-gliadin-derived antigen AAQ6C were elevated in patients with schizophrenia when compared with healthy controls (Table 2)
Summary
Schizophrenia is a complex psychiatric disorder, demonstrating heterogeneity in clinical presentation with a combination of positive, negative and cognitive symptoms.[1]. The outcomes have been inconsistent, studies have attempted to examine the efficacy of gluten-free diets in the treatment of schizophrenia, demonstrating improvement of clinical scales and earlier recovery in some patients treated with gluten-free diets.[10,11,12,13] Case studies in the literature have further demonstrated the induction of psychiatric and schizophrenia-like symptoms in response to gluten challenge and the resolution of these symptoms with gluten-free diets.[14,15]
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