T cells are associated with negative symptoms in persons with anti-gliadin antibody positive schizophrenia and related disorders.
Level 4 - case-series / case-control
Cross-sectional observational study evaluating immune markers and symptom correlations across patient subgroups
PubMed 40857980 · doi:10.1016/j.schres.2025.08.008
What was done
Researchers evaluated 26 clinically stable, medicated individuals with schizophrenia and related disorders (SRD) stratified by anti-gliadin IgG antibody status (AGA+ [≥20 U] vs AGA−). Negative symptoms were measured using the Scale for the Assessment of Negative Symptoms (SANS). Peripheral blood was assessed via ELISA for AGA-IgG, flow cytometry for pan-T cells (CD3+), helper T cells (CD3+CD4+), regulatory T cells (Tregs; CD3+CD4+CD25+Foxp3+), and activated Tregs (aTregs; CD3+CD4+CD25+Foxp3+CD45RA−), alongside multiplex profiling of circulating inflammatory markers.
What was found
46% of participants were AGA+. Within the AGA+ group, the proportion of aTregs was significantly increased (p = 0.0061). Higher pan-T cell proportions correlated with higher SANS total, anhedonia, avolition, and alogia scores (all p < 0.05). Conversely, higher helper T cells correlated with lower SANS total, blunting, anhedonia, and alogia scores (all p < 0.05), and higher Tregs correlated with lower SANS total, anhedonia, and alogia scores (all p < 0.05). AGA+ individuals also exhibited elevated circulating immune markers consistent with a pro-inflammatory phenotype.
Why it matters
The findings highlight a potential immunological subset of schizophrenia linked to gluten sensitivity, where regulatory T cells may buffer against negative symptoms while other T-cell subsets may exacerbate them.
Limits
The sample size was very small (n = 26 total), substantially limiting statistical power and subgroup analyses. The cross-sectional design cannot establish whether T-cell alterations cause or result from symptom severity. All participants were medicated, which may confound immune measurements, and specific pathogenic T-cell subsets driving the negative correlations were not isolated.
Cited by
- context Approximately 17% of people with schizophrenia have elevated gluten antibodies.