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

ABSTRACT 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.