Elevated Peripheral <scp>IL</scp> ‐ <scp>17A</scp> ‐Enriched <scp>CD161</scp> ⁺ <scp>CCR6</scp> ⁺ <scp>CD4</scp> ⁺ 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.