Deltex1 suppresses T cell function and is a biomarker for diagnosis and disease activity of systemic lupus erythematosus. (9th January 2019)

• Record Type: Journal Article
• Authors: Leu, Chuen-Miin; Hsu, Tzu-Sheng; Kuo, Yu-Ping; Lai, Ming-Zong; Liu, Po-Chun; Chen, Ming-Huang; Chang, Deh-Ming; Tsai, Chang-Youh; Chen, Ming-Han
• Is Part Of: Rheumatology. Volume 58:Number 4(2019)
• Page Start: 719
• Page End: 728
• Publication Date: 2019-01-09
• Subjects: Deltex1 -- SLE -- T cell; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/key418
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objective: Deletion of Deltex1 (DTX1) in mice caused hyperactivation of T cells and lupus-like autoimmune syndromes, however, the association of DTX1 with human autoimmune diseases is totally unknown. This study investigated the role of DTX1 in human T cell functions and its correlation with disease activity in patients with SLE. Methods: The influence of DTX1 on T cell function was evaluated using human primary cells. DTX1 expression in peripheral blood mononuclear cells (PBMCs) from healthy controls and SLE patients was measured by quantitative real-time PCR and the SLEDAI was used to assess disease activity. Results: After stimulation with anti-CD3 and anti-CD28, silencing of DTX1 expression enhanced IFN-γ secretion by human T cells. The expression of DTX1 in PBMCs was significantly lower in 100 SLE patients than in 50 age- and sex-matched healthy controls (DTX1/glyceraldehyde 3-phosphate dehydrogenase, 0.452 vs 1.269, P < 0.001). The area under the receiver operator characteristics curve of the model was 0.737 (95% CI 0.658, 0.815). Intriguingly, a low DTX1 level in T cells led to high IFN-γ production in SLE patients and had a correlation with severe disease activity. In addition, low DTX1 expression in SLE patients was associated with active LN, lung involvement or hypocomplementaemia. Conclusion: Knockdown DTX1 expression in human T cells reduced IFN-γ secretion. DTX1 expression in the PBMCs was significantly lower in SLE patients and had an inverse correlation with disease activity, indicating that the DTX1 level may be a good disease marker of SLE.