Thirty-five percent of people with schizophrenia-related disorders (SRD) form a high-inflammation subgroup defined by elevated anti-gliadin antibodies (AGA+) and inflammatory proteins and associated with an increased severity of negative symptoms. However, the immune mechanisms mediating these effects remain poorly defined. Here, we characterized transcriptional signatures of peripheral immune cells in AGA+ SRD (n=7) compared to AGA-negative (AGA-) SRD (n=3) and healthy controls (HC; n=5), using single-cell RNA-sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs). AGA+ SRD was associated with increased abundance of T-helper-17 cells (Th17), T-follicular helper-1 (Tfh1), CD5+ B cells, plasmacytoid dendritic cells (pDCs), and several CD8+ T cell subsets, including memory and Natural Killer-T-like activated subsets. In parallel, AGA- SRD exhibited a higher abundance of several monocyte subsets compared to either AGA+ SRD or HC. Pathway analysis revealed upregulation in AGA+ SRD of JAK/STAT, type I Interferon, and IL-6 signaling pathways in distinct subset of activated T-cells. Collectively, these results define a unique T cell predominant inflammatory signature in AGA+ SRD, as well as potential targets for therapeutic intervention.
Salem, D., O'Hara-Payne, R., Clark, S., Cortes-Gutierrez, M., Singh, N. J., Roche, D. J. O., Kelly, D., Ament, S. A.
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