Reduced Deltex1 expression in T cells indicates increased disease activity in Sjögren's disease

Abstract

Objectives: Deltex1 is a transcriptional target of NFAT that promotes T cell anergy. However, whether Deltex1 affects the properties of regulatory T cells (Tregs), which are involved in the pathogenesis of Sjögren's disease (SjD), is unknown.

Methods: T cells were purified from peripheral blood using a negative selection method. Deltex1 mRNA levels were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The mean fluorescent intensity (MFI) of Treg-associated molecules and the cytokine positivity of CD4+ FoxP3+ Tregs were analysed using flow cytometry. The European League against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) and Patient- Reported Index (ESSPRI) were used to evaluate systemic disease activity and symptoms in SjD.

Results: Deltex1 expression in T cells was significantly lower in SjD patients than in age- and sex-matched healthy controls (p<0.001). Deltex1 mRNA levels in T cells negatively correlated with visual analog scale scores for fatigue, ESSDAI, and ESSPRI (r=-0.334, p=0.035; r=-0.364, p=0.021; and r=-0.340, p=0.032, respectively). Low Deltex1 levels correlated with some clinical manifestations of SjD, including immune thrombocytopenia, vasculitis, and autoimmune thyroiditis (p=0.014, 0.002, and 0.001, respectively). The MFI of PD-1, CTLA-4, TIM-3, LAG-3 on Tregs and the percentage of interferon-γ+, interleukin (IL)-4+, IL-17A+ Tregs were significantly higher in the low Deltex1 group (Deltex1/GAPDH ≤0.02) than in the high Deltex1 group (Deltex1/GAPDH > 0.02) (p<0.05).

Conclusions: Deltex1 may affect the properties of Tregs; thus, it is a potential biomarker of disease activity in SjD.