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

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.

Autoimmune phenotypes in schizophrenia reveal novel treatment targets

“…This connection between gluten exposure and psychiatric disorders was first hypothesized by FC Dohan who observed that psychiatric hospitalization rates in Europe strongly correlated with the amount of wheat consumption, which varied considerably during and immediately after World War II (Dohan, 1966a, 1966b). Since then, numerous studies and meta-analyses have examined the association of food antigens with schizophrenia and with varied results (Cascella et al, 2011; Dickerson et al, 2010; Jin et al, 2010; McLean et al, 2017; Reichelt and Landmark, 1995; Reichelt et al, 1995; Samaroo et al, 2010; Severance et al, 2010). In our studies, these gluten antibody profiles correlated with measures of GI inflammation (Severance et al, 2012a; Severance et al, 2012b; Severance et al, 2013).…”

The Differences between Gluten Sensitivity, Intestinal Biomarkers and Immune Biomarkers in Patients with First-Episode and Chronic Schizophrenia

“…In some studies, no differences in antibody titer against gluten components were shown between healthy individuals and schizophrenia patients [ 44 , 45 ]. However, despite the unchanged immune response of patients, Severance et al observed a relationship between the level of antibodies to gluten in blood serum and their level in cerebrospinal fluid [ 44 ].…”

An examination of plasma autoantibodies against voltage gated calcium channels in schizophrenia

“…In order to measure plasma levels of IgG against the peptides antigens derived from CACNA1I and CACNA1C proteins, an in-house ELISA was developed, as previously detailed ( McLean et al, 2017 ). Briefly, the synthetic peptides were coated to a sulfhydryl 96-well plate (Corning, USA) at 20 μg/mL and incubated for 1.5 h at room temperature.…”