THU0317 EXPANDED DOUBLE NEGATIVE T CELLS IN PATIENTS WITH ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY ASSOCIATED VASCULITIS PRODUCE CYTOKINES AND INDUCE RENAL DAMAGE
Authors: Y. Qin, J. Luo, Y. Wang, C. Gao
Journal: Annals of the Rheumatic Diseases (2020)

Background: Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are recognized as a small-vessel vasculitis of autoimmune origin characterized by inflammation and the presence of circulating ANCA with the major target antigens identified as proteinase 3 (PR3) and myeloperoxidase (MPO). A very minor T cell subpopulation which lacks both CD4 and CD8 markers, known as CD4-CD8- double negative (DN) represents less than 5% of the total peripheral blood (PB) T cells in healthy individuals and plays a vital role in the pathogenesis of autoimmune disorders. Objectives: To investigate whether DN T cells and cytokine (IFN-γ, IL-4 and IL-17) are involved in the pathogenesis of AAV and to verify whether DN T cells are associated with kidney damage. Methods: Nineteen healthy controls (HCs) and 40 active patients with AAV were enrolled in this study. Peripheral blood mononuclear cells from AAV patients and controls were isolated by magnetic bead separation, and phenotypic characterisation of mononuclear cells were determined via flow cytometry. The diagnostic value for DN T subsets was evaluated by the areas under the receiver operating characteristic curves (AUC). Results: The percentage (p&lt;0.001) and absolute numbers (p=0.028) of DN T cells were found to be significantly higher in patients with AAV as compared with controls. Less the percentage of DN T cells from patients with AAV were of CD62L+CD45RO+ (p=0.024) phenotype than was found in HCs, and the percentage of CD62L-CD45RO- (p=0.043) was higher. The percentage of DN T cells expressing IFN-γ (p=0.032), IL-4 (p=0.039) and IL-17 (p=0.042) increased in AAV patients. In AAV with renal damage, the percentage of DN T cells was expanded (p=0.016) than those patients without renal damage. After conventional methylprednisolone treatment, the percentage of DN T cells in patients with remission was significantly lower than those active patients (p=0.028). The ROC curve analysis showed that the ratios of CD4+ T cells to DN T cells and CD8+ T cells to DN T cells were useful in diagnosing AAV patients. The AUCs were 0.967 (95% confidence interval [CI] 0.922-1.000; p&lt;0.001) and 0.879 (95%CI 0.789-0.969; p&lt;0.001), respectively. Conclusion: DN T cells represent a inflammatory T cell subset that produces inflammatory cytokines (IFN-γ, IL-4 and IL-17) in AAV patients. Suppression of DN T cells may be new specific treatment in autoimmune disorder such as AAV. References: [1]Geetha D, Jefferson JA. ANCA-Associated Vasculitis: Core Curriculum 2020. Am J Kidney Dis. 2019 Jul; pii: S0272-6386(19)30826-1. [2]Tedesco M, Gallieni M, Pellegata F. Update on ANCA-associated vasculitis: from biomarkers to therapy.J Nephrol. 2019 Jul 12. doi: 10.1007/s40620-019-00628-9. [Epub ahead of print]. [3]Nicholas Crispe I. CD4/CD8-negative T cells with ab antigen receptors. Curr Opin Immunol 1994;6:438-441. [4]Dean GS, Anand A, Blofeld A, et al. Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with systemic lupus erythematosus: production of IL-4. Lupus 2002;11:501-507. [5]Liu MF, Yang CY, Chao SC, et al. Distribution of Double-Negative (CD4-CD8-, DN) T Subsets in Blood and Synovial Fluid from Patients with Rheumatoid Arthritis[J]. Clinical Rheumatology, 1999, 18(3):227-231. [6]Alunno A, Bistoni O, Bartoloni E, et al. IL-17-producing CD4-CD8- T cells are expanded in the peripheral blood, infiltrate salivary glands and are resistant to corticosteroids in patients with primary Sjogren’s syndrome [J]. Annals of the Rheumatic Diseases, 2013, 72(2):286-292. Disclosure of Interests: None declared