Pan T cells, Helper T cells, and Regulatory T cells are Associated with Negative Symptoms in Persons with Anti-Gliadin Antibody Positive Schizophrenia and Related Disorders

BackgroundAbout one in three persons with a schizophrenia related disorder (SRD) have elevated anti-gliadin IgG antibodies (AGA). This AGA positive (AGA+) subgroup of SRD clinically has a higher burden of negative symptoms and are symptoms associated with high functional impairments with a lack of effective therapeutics. Alterations in T cells have been demonstrated in SRD, and we have previously shown regulatory T cells (Tregs) are increased and correlate with fewer negative symptoms in persons with SRD compared with healthy controls. MethodsTo further elucidate the role of the immune system in AGA+ SRD pathology, we investigated the relationship of T cells and negative symptoms in 26 medicated and clinically stable persons with SRD. Participants had blood drawn; AGA-IgG measured by ELISA (AGA positive defined as [&ge;]20 U); had flow cytometry performed 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+RA-); had serum cytokines measured; and completed the Scale for the Assessment of Negative Symptoms (SANS) to measure negative symptoms. Results46% of persons with SRD in this study were AGA+ and, in this group specifically, pan-T cells were correlated with worse SANS total, anhedonia, alogia, and avolition (p<0.05), while helper T cells and Tregs were correlated with less negative symptoms (respectively, SANS total and alogia; SANS total, anhedonia, alogia; P<0.05). AGA+ persons with SRD also had several elevated serum cytokines, corresponding with a broadly pro-inflammatory phenotype. ConclusionsThese hypothesis-generating findings highlight T cell dysfunction in AGA+ positive SRD, suggesting Tregs protecting against negative symptom severity but also an unidentified other T cell population to possibly be driving negative symptom severity.