Elevated Peripheral IL-17A-Enriched CD161 + CCR6 + CD4 + T Cells and Their Diagnostic Value in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease marked by dysregulated T cell responses and elevated pro-inflammatory cytokines such as IL-17A. Identifying reliable biomarkers could improve diagnosis and understanding of SLE pathogenesis. This study aimed to characterise CD161 and CCR6 expression on peripheral T cells in SLE and evaluate their diagnostic potential. Peripheral blood mononuclear cells were obtained from 34 new onset SLE patients, 26 primary Sjögren's syndrome (pSS) patients and 20 age- and sex-matched healthy controls. Flow cytometry profiled CD4+ and CD8+ T cells for CD161, CCR6, CXCR3 and intracellular IL-17A. Standard laboratory assays measured complete blood counts, CRP, ESR, complement, immunoglobulins and autoantibodies. Statistical analyses included Student's t-test, Mann-Whitney test, or ANOVA for group comparisons, Spearman's correlation and receiver operating characteristic (ROC) curve analysis with cut-offs determined by the Youden index. A distinct CD4+CD161+CCR6+ subset was present in healthy blood and showed significantly higher IL-17A than CD161+CCR6- or CD161-CCR6+ cells. In SLE patients, the frequency of CD4+CD161+CCR6+ cells was markedly increased compared to healthy controls (median 18.0% vs. 9.2%, p < 0.001) and CD4+CD161+ alone was also elevated (p < 0.05). ROC analysis distinguishing SLE from healthy controls yielded AUCs of 0.993 for CD4+CD161+, 0.774 for CD4+CD161+CCR6+ and 0.526 for CD4+CCR6+. Using pSS as disease controls, CD4+CD161+CCR6+ cells achieved an AUC of 0.868. CD161+CCR6+ CD4+ T cells are enriched for IL-17A and significantly elevated in early SLE, demonstrating moderate diagnostic accuracy. These findings support their potential role as novel blood biomarkers for SLE.