Work

T cells are associated with negative symptoms in persons with anti-gliadin antibody positive schizophrenia and related disorders

Year: 2025

Type: article

Abstract: Background About one-third of persons with schizophrenia and related disorders (SRD) have elevated anti-gliadin IgG antibodies (AGA), associated with gluten sensitivity, increased negative symptoms, greater functional impairments, and limited therapeutic options. Alterations in T cells have been demonstrated in SRD, and we have previously shown that regulatory T cells (Tregs) are increased and correlate with fewer negative symptoms in SRD. Methods We investigated the relationship of T cells and negative symptoms in 26 clinically stable, medicated persons with AGA positive (AGA+) or AGA negative (AGA-) SRD. Negative symptoms were evaluated using the Scale for the Assessment of Negative Symptoms (SANS). Blood samples were analyzed for: 1) AGA-IgG levels (measured by ELISA; AGA positivity defined as ≥20U), 2) flow cytometry to quantify proportions of pan-T cells (CD3 + ), helper T cells (CD3 + CD4 + ), Tregs (CD3 + CD4 + CD25 + Foxp3 + ), and activated Tregs (aTregs) (CD3 + CD4 + CD25 + Foxp3 + CD45RA − ) and 3) multiplex analysis of circulating immune markers. Results 46 % of SRD participants were AGA+ and in this group, aTregs were increased in proportion (p = 0.0061). In AGA+ SRD, pan-T cells were correlated with higher SANS total, anhedonia, avolition and alogia scores (all p < 0.05), while increased helper T cells and Tregs were correlated with less negative symptoms (respectively, SANS total, blunting, anhedonia, and alogia; SANS total, anhedonia, alogia; all p < 0.05). AGA+ SRD also had several elevated immune markers, corresponding with a pro-inflammatory phenotype. Conclusions These hypothesis-generating findings suggest T cell dysfunction in AGA+ SRD, suggesting Tregs mitigating negative symptom severity, but also an unidentified other T cell population possibly contributing to negative symptomatology.

Source: Schizophrenia Research

DOI: 10.1016/j.schres.2025.08.008