GPR56 and CD319 identify distinct cytotoxic-associated DP and DN T-cell subsets in early systemic lupus erythematosus.

OBJECTIVE: To characterize the expression patterns of GPR56 and CD319 across peripheral blood T-cell subsets, including CD4⁺, CD8⁺, double-positive (DP), and double-negative (DN) T-cells, and to evaluate their potential diagnostic value and clinical relevance in systemic lupus erythematosus (SLE). METHODS: Peripheral blood samples from 34 newly diagnosed, treatment-naïve SLE patients and 29 age- and sex-matched healthy controls were analyzed by flow cytometry. The frequencies of GPR56⁺ and CD319⁺ cells within CD4⁺, CD8⁺, DP, and DN T-cell subsets, together with their co-expression of cytotoxic molecules granzyme B and perforin, were evaluated. Clinical parameters, autoantibody profiles, complement levels, and hematological indices were collected. Group comparisons, correlation analyses, receiver operating characteristic (ROC) analyses, and multivariable logistic regression models incorporating eight GPR56- and CD319-associated parameters were performed. RESULTS: GPR56 and CD319 were preferentially expressed on DP and DN T-cells and strongly associated with cytotoxic effector molecules. Compared with healthy controls, SLE patients exhibited increased frequencies of GPR56⁺ cells within CD4⁺CD8⁻, DP, and CD4⁻CD8⁺ T-cell subsets, whereas CD319⁺ cells displayed subset-dependent alterations, with increased frequencies in CD4⁺CD8⁻ and CD4⁻CD8⁺ T-cells but decreased frequencies in DN T-cells. GPR56⁺ and CD319⁺ CD4⁺CD8⁻ T-cells were positively associated with anti-Sm and anti-U1RNP antibodies, while reduced CD319⁺ DN T-cells correlated with lower serum C3 levels. Among individual parameters, CD319⁺ DN T-cells showed the highest diagnostic performance for early SLE identification. A combined logistic regression model incorporating all eight parameters achieved excellent discrimination between SLE patients and healthy controls (AUC = 0.926). CONCLUSION: GPR56 and CD319 identify cytotoxic-associated DP and DN T-cell populations with distinct alterations in newly diagnosed SLE. Integrated assessment of GPR56- and CD319-associated T-cell subsets may provide complementary biomarkers for early SLE identification and warrants further validation in larger cohorts.