Peripheral CHOP+ CD4+ T-Cell Subsets Are Reduced and Clinically Relevant in Primary Sjögren's Syndrome.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands and systemic immune dysregulation. Endoplasmic reticulum stress (ERS)-related transcription factor C/EBP homologous protein (CHOP) has been implicated in several autoimmune conditions, but its role in pSS remains unclear. This study aimed to delineate CHOP expression across peripheral CD4+ T-cell subsets in pSS and evaluate their clinical and diagnostic relevance, and investigate whether CHOP alterations were associated with the apoptotic response to ER stress. METHODS: Peripheral blood mononuclear cells from 28 newly diagnosed, treatment-naïve pSS patients and 25 age- and sex-matched healthy controls were analyzed by flow cytometry for CHOP expression in CD4+, CD8+, and regulatory T-cell (Treg) subsets. Standard laboratory tests measured complement, immunoglobulins, and autoantibodies. Additional experiments assessed apoptosis of CD4+ T cells after tunicamycin-induced ER stress. Group comparisons used Student's t-test or Mann-Whitney U test, correlations used Spearman's coefficient, and receiver operating characteristic (ROC) curves assessed diagnostic performance. RESULTS: CHOP was expressed at higher levels in CD4+ than CD8+ T cells in healthy individuals, with effector and central memory CD4+ subsets showing the greatest expression. pSS patients exhibited significantly reduced proportions of CHOP+ CD4+ T cells-including non-Treg and memory subsets-compared with controls. Within Tregs, CHOP expression was enriched in effector Tregs in health but selectively diminished in pSS. CHOP+ Treg subsets showed differential correlations with serum IgG, IgA, anti-Sm antibodies, and complement C4. ROC analysis yielded AUCs >0.90 for several CHOP+ CD4+ subsets distinguishing pSS from controls. CONCLUSION: Peripheral CHOP+ CD4+ T-cell subsets are quantitatively reduced and serologically linked to autoantibody production in pSS. Their high diagnostic accuracy highlights CHOP expression as a potential blood biomarker and mechanistic target in pSS.