SAT0459 Low dose IL-2 restores imbalance between TH17 and regulatory T cells in patients with psoriatic arthritis. (15th June 2017)

• Record Type: Journal Article
• Authors: Qin, K; Chen, Q; Fan, J; Xu, D; Li, X; Wang, C; Gao, C
• Is Part Of: Annals of the rheumatic diseases. Volume 76(2017)Supplement 2
• Page Start: 947
• Page End: 947
• Publication Date: 2017-06-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2017-eular.6027
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Psoriasis arthritis is one of chronic, relapsing, inflammatory autoimmune disorders with skin lesions and joint damage. A therapeutic revolution of psoriatic arthritis (PsA) is still a considerable unmet need in the past decades. It has been well known that the imbalance of Th17 cells and regulatory T cells (Tregs) may be a pivotal cause of PsA. Correction of this dysfunction can be a potential therapy of PsA. Objectives: In this study, we measured and compared both absolute numbers and proportions of CD4+CD17+ Th17 cells and CD4+CD25+Foxp3+ Treg cells in peripheral blood of PsA patients and healthy controls to explore the immunopathogenesis of PsA; on the other hand, the effects of low-dose recombinant human IL-2 (rhIL-2) on Th17 and Treg cells were investigated in patients with PsA. Methods: Both absolute numbers and proportions of Treg and Th17 cells in peripheral blood, defined as the CD4+CD25+Foxp3+T or CD4+IL-17+ T cell populations, were examined by flow cytometry in 40 healthy controls and 77 patients with PsA, including 39 patients who had never received disease-modifying antirheumatic drugs (DMARDs) and 38 patients who were receiving or had received DMARDs. Among these patients, 20 patients consented at enrollment to receive rhIL-2 treatment. Before and after treatment (50WIU/d for 5 days, IH), Th17 and Treg cells in peripheral blood were analyzed by flow cytometry. Results: The absolute count of Th17 cells in patients with PsA was very significantly higher than that of healthy controls (P<0.01), but the proportions of Th17 cell were not seen difference between PsA and healthy controls (P>0.05). In contrast with treated-PsA patients, the absolute count of Th17 cells was significant higher in untreated-PsA patients (P<0.05). After the course of rhIL-2 treatment, there was a significant increase in the absolute count of Treg cells (P<0.05), but no diference in the absolute count of Th17 cells, Th17/Treg was significantly lower and went back to nomal. Conclusions: The results suggest that, not the proportion, but the decrease in the absolute count of Th17 cells, defined as the CD4+CD17+ populations, contributes to the pathogenesis of PsA. After the treatment of rhIL-2, there was a more significant increase in the absolute count of Treg cells than that of Th17, and consequently the balance of Th17/Treg was restored to normal, leading to the development of new therapies. References: Karczewski J, Dobrowolska A, Rychlewskahańczewska A, et al. New insights into the role of T cells in pathogenesis of psoriasis and psoriatic arthritis[J]. Autoimmunity, 2016:1.DOI:10.3109/08916934.2016.1166214. Yoo I S, Lee J H, Song S T, et al. T-helper 17 cells: the driving force of psoriasis and psoriatic arthritis.[J]. International Journal of Rheumatic Diseases, 2012, 15(6):531–537. DOI:10.1111/j.1756–185X.2012.01813.x. Szodoray P, Nakken B, Barath S, et al. Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders[J]. Human Immunology, 2013, 74(12):1510–8. DOI:10.1016/j.humimm.2013.08.003. Raychaudhuri S P. Role of IL-17 in psoriasis and psoriatic arthritis.[J]. Clinical Reviews in Allergy & Immunology, 2013, 44(2):183–193. DOI: 10.1007/s12016–012–8307–1. Disclosure of Interest: None declared