Enhanced co-expression of TIGIT and PD-1 on γδ T cells correlates with clinical features and laboratory parameters in patients with primary Sjögren's syndrome.

OBJECTIVES

The research aimed to assess the proportions of Gamma delta (γδ) T cells and the expression levels of CD226, ICOS, CD40L, OX40, TIGIT, LAG-3, Tim-3, and PD-1 on γδ T cells in the peripheral blood of patients diagnosed with primary Sjögren's syndrome (pSS), and to evaluate the clinical significance of these findings.

METHODS

Utilizing flow cytometry, we investigated the proportion of γδ T cells and the expression of CD226, ICOS, CD40L, OX40, TIGIT, LAG-3, PD-1, and Tim-3 on γδ T cells in 37 patients diagnosed with pSS and 28 healthy controls (HC). Moreover, we explored the potential associations between the proportion of γδ T cells, TIGIT + γδ T cells, PD-1 + γδ T cells, and TIGIT + PD-1 + γδ T cells with clinical symptoms and laboratory parameters.

RESULTS

Compared to HC, patients with pSS showed a decreased proportion of γδ T cells, alongside an increased proportion of TIGIT + γδ T cells, PD-1 + γδ T cells, and TIGIT + PD-1 + γδ T cells (p < 0.01). Nevertheless, there were no statistically significant variations noted in the expression levels of CD226, ICOS, CD40L, Tim-3, LAG-3, and OX40 on γδ T cells between two groups (p > 0.05). Furthermore, γδ T cells demonstrated a declining trend in patients with clinical symptoms such as xerostomia, xerophthalmia, decayed teeth, and fatigue, as well as in those with high IgG levels and positivity for anti-SSB/La, anti-SSA/Ro60, and anti-SSA/Ro52. Conversely, TIGIT + γδ T cells, PD-1 + γδ T cells, and TIGIT + PD-1 + γδ T cells exhibited an increasing trend in these patient groups. In correlation analyses with IgG, ESR, CRP, C3, C4, IgA, RF, IgM, and ESSDAI, γδ T cells were observed to have a negative correlation with ESR, IgG and ESSDAI. TIGIT + γδ T cells demonstrated significant positive correlations with IgG, IgA, and ESSDAI. PD-1 + γδ T cells showed positive correlations with ESR, CRP, IgA, and ESSDAI. Furthermore, TIGIT + PD-1 + γδ T cells showed significant positive correlations with ESR, IgG, RF, IgA, and ESSDAI.

CONCLUSION

Our results indicated that patients with pSS exhibited a reduction in γδ T cells alongside elevated expression of TIGIT, PD-1, and their co-expression on γδ T cells. These changes were found to correlate with clinical symptoms and laboratory parameters, suggesting that γδ T cells, TIGIT + γδ T cells, PD-1 + γδ T cells, and especially TIGIT + PD-1 + γδ T cells could potentially serve as diagnostic biomarkers for pSS.