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.