POS0932 REGULATION OF INTESTINAL FLORA RESTORES IMMUNE BALANCE IN PATIENTS WITH UNDIFFERENTIATED SPONDYLOARTHRITIS

Background:Undifferentiated spondyloarthritis (USpA) is the most common subtype of the spondyloarthritides with a prevalence between 0.7% and 2.0%1. Inflammatory back pain, peripheral arthritis and less frequently enthesitis are the main clinical features of USpA2. Resently the role of dysregulated microbiome along with migration of T lymphocytes and other cells from gut to the joint (“gut-joint” axis) has been recognized3 4. However, the detailed lymphocyte statuses of USpA patients and the effect of regulating the intestinal flora on the lymphocyte subsets is unclear.Objectives:To investigate the status of lymphocyte subsets in peripheral blood (PB) of USpA patients and the variation after regulation of intestinal flora.Methods:A total of 39 newly diagnosed patients with USpA who fulfilled the European Spondyloarthropathy Study Group (ESSG) classification criteria and 60 age- and sex- matched healthy controls (HC) were enrolled in this study. All patients were given intestinal flora regulation therapy for six months, including clostridium butyricum capsule or bacillus coagulans tablet. The peripheral lymphocyte subsets of these participants were assessed by flow cytometry. Methane hydrogen breath test as well as cytokines were measured in all patients before and after treatment. Mann-Whitney U test was applied for the lymphocyte status between USpA patients and HC and Wilcoxon test for the comparison before and after treatment. The results of methane hydrogen breath were counted by the Chi-Square test. All P-values reported herein are two-tailed and P-value<0.05 was taken as statistically significant.Results:Compared with HC, patients with USpA had a lower numbers of T cells (P=0.001), NK cells (P=0.026), CD8+T cells (P=0.046) and Treg cells (P<0.05) but higher ratios of Th17/Tregs (P=0.001), indicating a disturbance of immune microenvironment (Figure 1). After given therapy, T cells (P=0.003), B cells (P=0.018), NK cells (P=0.003), CD8+T cells (P=0.001) and Treg cells (P=0.009) were distinctly increased while the ratio of Th17/Treg decreased (P=0.046), suggesting a rebalance of immune systems (Figure 2a-c). Moreover, there were increase in the level of IL-6 (P<0.001), IL-17 (P=0.029) and TNF-α (P=0.003) as well as decrease in IL-10 (P=0.045) and IFN-γ (P=0.001) (Figure 2d). Further, the positive rate of intestinal bacterial overgrowth decreased significantly after regulation (P=0.029) (Figure 2e).Conclusion:Imbalance of immune environment is closely related to the incidence of undifferentiated spondyloarthrosis. The regulation of intestinal flora restores the balance and improve the growth of bacteria in the small intestine simultaneously. Therefore it is essential to focus on the alteration of intestinal flora to prevent the outbreak of inflammation and disease progression.References:[1]Cruzat V, Cuchacovich R, Espinoza LR. Undifferentiated spondyloarthritis: recent clinical and therapeutic advances. Curr Rheumatol Rep 2010;12(5):311-7. doi: 10.1007/s11926-010-0115-0 [published Online First: 2010/07/16].[2]Deodhar A, Miossec P, Baraliakos X. Is undifferentiated spondyloarthritis a discrete entity? A debate. Autoimmun Rev 2018;17(1):29-32. doi: 10.1016/j.autrev.2017.11.006 [published Online First: 2017/11/08].[3]Sheth T, Pitchumoni CS, Das KM. Management of Musculoskeletal Manifestations in Inflammatory Bowel Disease. Gastroenterol Res Pract 2015;2015:387891. doi: 10.1155/2015/387891 [published Online First: 2015/07/15].[4]Fragoulis GE, Liava C, Daoussis D, et al. Inflammatory bowel diseases and spondyloarthropathies: From pathogenesis to treatment. World J Gastroenterol 2019;25(18):2162-76. doi: 10.3748/wjg.v25.i18.2162 [published Online First: 2019/05/31].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

AB0677 REVISING THE DEFINITION OF REACTIVE ARTHRITIS AND DIFFERENTIATION FROM UNDIFFERENTIATED SPONDYLOARTHRITIS

Background:Reactive arthritis (ReA) is defined by 1999 ACR criteria as arthritis preceding a bacterial genitourinary (GUS) or gastrointestinal (GIS) infection in 3 days-6 weeks and evidence of triggering infection. Recently, ReA is classified as SpA and patients who do not fulfill SpA criteria are classified as undifferentiated spondyloarthritis (USpA) according to ASAS/EULAR SpA classification criteria.Objectives:In several case reports which are associated with other infective agents are reported and the definition is extended for some clinicians so that SpA which is occurred after any infection is called as ReA. On the other hand, some researchers still accept the classical definition of ReA. The problem with the heterogeneity of opinions and unstandardized definition of ReA hinders studies about pathogenesis and standardization of treatments. In this study, we aimed to determine the spectrum of the use of the definition of reactive arthritis in publications in PubMed between 2009-2019.Methods:The ReA keyword is searched in PubMed for the years between 2009-2019. 248 different publications have been identified and included in this research. 89 articles, 47 reviews, 108 case reports, 2 guidelines, and 2 editorials reviewed for the definition of ReA.Results:Only 42.7% (106 patients) of these publications meet the classical definition which suggests ReA after only GIS and GUS infections. In 4 (1.6%) of the publications ReA was defined after GIS, GUS and oropharyngeal infections; in 3 (1,2%) of the publications after any bacterial infection; in 9 (3.6%) of the publications after any infection. In 8 (3.2%) of the publications, ReA and USPA was used correspondingly. In 39 (15,7%) of the publications the term agent related, ReA was used without making a general definition for ReA. 79 publications (31,9%) have not defined ReA.According to causative agent and ReA relationship, in 64 (24,6%) general infective agents, in 75 (30,2%) classical agents, in 22 (8,9%) other bacterial agents, in 23 (9,3%) streptococcus, in 10(4%) intravesical BCG, in 6 (2.4%) HIV, in 6 (2.4%) tuberculosis, in 12 (4,8%) clostrudium difficle, in 2 (0.8%) parasites were reported. In 31 (12,5%) of the publications the causative agent for the ReA was unknown, the diagnosis was made clinically.Conclusion:In this study, it is aimed to draw attention terminology intricacy and the need for the standardization of the definition of ReA and USpA. It is clear that to standardize the definition of Rea and USpA is necessary. Between 2009-2019 there are reported cases diagnosed as ReA associated with bacterial infections (especially with Clostridium difficile, streptococcus and tuberculosis infections), and viral infections (by a majority with HIV), and parasitic infections. It is not clear if we need to define them classically or define them as USPA. Another important consideration is the necessity of extended laboratory investigations to find out the real causative agent even if the patient is clinically diagnosed with ReA. The requirement of the differentiation between ReA and USpA must be revealed for therapeutic researches.References:[1]A proposal for the classification of patients for clinical and experimental studies on reactive arthritis. Pacheco-Tena C, Burgos-Vargas R, Vázquez-Mellado J, Cazarín J, Pérez-Díaz JA. J Rheumatol. 1999 Jun;26(6):1338-46.[2]The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Rudwaleit M, van der Heijde D, Landewé R, Akkoc N, Brandt J, Chou CT, Dougados M, Huang F, Gu J, Kirazli Y, et al. Ann Rheum Dis. 2011;70:25–31.Disclosure of Interests:None declared