Transcriptomic Profiling of PBMCs via Bulk RNA-Sequencing in Posner-Schlossman Syndrome Reveals Immune Dysregulation and Altered Viral Response

PURPOSE: To explore systemic immune transcriptional signatures in Posner-Schlossman syndrome (PSS) across acute and intermittent phases. METHODS: = 3). Two patients were sampled in both phases; within-subject correlation was not modeled in differential-expression analyses. Differential expression was assessed using DESeq2, pathways were examined using the Kyoto Encyclopedia of Genes and Genomes, and immune-cell-associated marker expression was compared using CAMERA gene set testing with linear model contrasts. Plasma IFITM2, ISG15, and SOCS1 were measured by ELISA in an independent cohort of 51 APSS patients and 69 healthy controls. RESULTS: Interferon-responsive and antiviral genes, including IFITM2, ISG15, and SOCS1, were downregulated in APSS. Plasma protein levels showed concordant decreases in the independent cohort. Genes encoding ubiquitin-proteasome components (SKP1, RBX1, PSMF1, PSMB2, PSMB3, and PSMD13) and cytokines associated with antigen presentation and adaptive immunity were downregulated, whereas cytokine genes linked to macrophage activity and innate immunity were upregulated. Post hoc comparisons showed reduced CD8+ T-cell-associated and increased macrophage-associated marker expression in APSS compared with both IPSS and controls. IPSS immune transcriptional profiles generally approached those of controls, consistent with reduced disease activity, although residual differences in macrophage-associated expression remained. CONCLUSIONS: These exploratory findings suggest altered systemic innate and adaptive immune regulation in PSS, with an increased monocyte/macrophage-associated transcriptional signature during acute attacks. They do not establish immune-cell proportions or cytomegalovirus-mediated mechanisms and cannot directly represent local anterior chamber pathology.