Clin Rheumatol. 2026 Oct 27.
OBJECTIVE: This study aimed to characterize the phenotypic profile of CD226⁺TIGIT⁺ mucosal-associated invariant T (MAIT) cells and investigate their association with Sjögren's disease (SjD).
METHODS: Peripheral blood mononuclear cells (PBMCs) from 35 newly diagnosed, treatment-naïve SjD patients and 34 age- and sex-matched healthy controls were analyzed by flow cytometry. MAIT cells were defined as CD3⁺TCRVα7.2⁺CD161^hi and stratified into CD4⁺, double-positive (DP), double-negative (DN), and CD8⁺ subsets. CD226 and TIGIT co-expression patterns were assessed across MAIT cell subsets. CD226/TIGIT-defined MAIT-cell phenotypes were further characterized for the surface expression of CD152, LAMP1, Tim-3, CD62L, and PD-1. Exploratory receiver operating characteristic (ROC) analyses were performed to assess their ability to discriminate SjD patients from healthy controls.
RESULTS: CD226⁺TIGIT⁺ MAIT cells were preferentially enriched in DP MAIT cells and exhibited a distinct checkpoint-enriched marker-expression profile characterized by higher surface expression of CD152 and LAMP1. Exploratory analyses in small phenotyping subsets suggested differential Tim-3, CD62L, and PD-1 expression across CD226/TIGIT-defined MAIT-cell phenotypes. Compared with healthy controls, patients with SjD displayed a significantly increased relative frequency of CD226⁺TIGIT⁺ MAIT cells, particularly within the CD4⁺ and DP MAIT subsets. However, the estimated absolute count of CD226⁺TIGIT⁺ MAIT cells did not differ significantly between the two groups, whereas the estimated absolute count of total MAIT cells was reduced in SjD, indicating relative enrichment of CD226⁺TIGIT⁺ MAIT cells within a contracted peripheral MAIT-cell compartment rather than numerical expansion. Exploratory ROC analysis demonstrated moderate discrimination between SjD patients and healthy controls, with an AUC of 0.754 for total CD226⁺TIGIT⁺ MAIT cell frequency.
CONCLUSION: CD226⁺TIGIT⁺ MAIT cells represent a phenotypically distinct, checkpoint-enriched MAIT-cell population associated with SjD. Their increased relative frequency within a reduced peripheral MAIT-cell compartment and distinct marker-expression profile highlight a disease-associated compositional and phenotypic difference rather than numerical expansion, while further studies in larger, clinically well-characterized cohorts are required to determine their functional significance and potential clinical relevance.
Keywords: CD226; MAIT cells; Sjögren’s disease; TIGIT