T Cells Expressing Ras Homolog Family Member a Display Enhanced Cytotoxicity but are Reduced in Lupus Peripheral Blood.

Abstract

Objective: This study aimed to explore the expression and clinical relevance of Ras homolog family member A (RhoA) in T cell subsets from patients with systemic lupus erythematosus (SLE).

Methods: Peripheral blood samples were obtained from newly diagnosed SLE patients and age- and sex-matched healthy controls. T cell subpopulations were analyzed by flow cytometry to quantify RhoA levels and associated cytotoxic markers, including granzyme B (GrB) and perforin (PFFN). Publicly available single-cell RNA sequencing (scRNA-seq) data were used to validate RhoA transcriptional patterns. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis.

Results: RhoA was unevenly distributed among circulating T cell populations, with the highest protein expression observed in CD8⁺ and effector memory subsets. RhoA⁺ T cells showed significantly higher GrB and PFN levels compared to their RhoA⁺ counterparts. In early-stage SLE, RhoA expression in T cells was significantly reduced compared to healthy individuals. However, a greater proportion of CD8⁺RhoA⁺ cells expressed GZMB in SLE patients. ROC analysis yielded area under the curve (AUC) values of 0.6720 for CD4⁺RhoA⁺ and 0.6635 for CD8⁺RhoA⁺ T cells.

Conclusion: RhoA⁺ T lymphocytes exhibit enhanced cytotoxic potential and may serve as early immunological markers for the identification of SLE.