FRI0299 Mucosal-associated invariant t cell deficiency in systemic lupus erythematosus is realted to an intrinsic defect in the ca2+/calcineurin/nfat1 signallingpathway

• Published in: Annals of the rheumatic diseases Vol. 77; no. Suppl 2; p. 686
• Main Authors: Park, Y.-W., Cho, Y.-N., Jin, H.-M., Kee, S.-J.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2018
• Subjects: Ankylosing spondylitis; Apoptosis; Autoimmune diseases; Behcet's syndrome; Calcineurin; Calcium signalling; CD8 antigen; Cell death; Disease; Flow cytometry; Interferon; Lupus; Lymphocytes T; Mucosal immunity; Natural killer cells; NF-AT1 protein; PD-1 protein; Peripheral blood; Rheumatic diseases; Rheumatoid arthritis; Signal transduction; Spondylitis; Synovial fluid; Systemic lupus erythematosus; T cell receptors
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2018-eular.6201

BackgroundMucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases.ObjectivesHere, we examined the level and function of MAIT cells in patients with rheumatic diseases.MethodsPatients with systemic lupus erythematosus (SLE; n=54), rheumatoid arthritis (RA; n=66), Behçet’s disease (n=9), ankylosing spondylitis (n=21), and healthy controls (n=136) were enrolled in the study. MAIT cell, cytokine and programmed death-1 (PD-1) levels were measured by flow cytometry.ResultsCirculating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. In particular, this MAIT cell deficiency was more prominent in CD8 +and double-negative T cell subsets, and significantly correlated with disease activity, such as SLE disease activity index (SLEDAI) and 28-joint disease activity score (DAS28). Interestingly, MAIT cell frequency was significantly correlated with natural killer T (NKT) cell frequency in SLE patients. IFN-gamma in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca2+/calcineurin/NFAT1 signalling pathway. In SLE patients, MAIT cells were poorly activated by alphagalactosylceramide-stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In RA patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood.ConclusionsOur study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.Disclosure of InterestNone declared