SAT0316 ANTI-PM/SCL ANTIBODIES IN SYSTEMIC SCLEROSIS: CLINICAL ASSOCIATIONS IN THE RESCLE COHORT

Background:Anti-PM/Scl antibodies are associated to systemic sclerosis (SSc) but are not specific to SSc. The true prevalence of anti-PM/Scl antibodies in SSc is unknown, ranging from 2.5% to 12.5%. An association between anti-PM/Scl antibodies with muscular involvement, pulmonary fibrosis, calcinosis, and a relatively benign prognosis have been described.Objectives:To compare the clinical manifestations and prognosis of SSc patients according the presence of anti-PM/Scl antibodies in the cohort of RESCLE (Spanish Scleroderma Registry).Methods:From the Spanish Scleroderma Study Group database, we selected patients in whom anti-PM/Scl antibodies had been tested. We compared demographic features, clinical manifestations, laboratory characteristics, and survival data between patients according the anti-PM/Scl antibodies status.Results:72 out of 947 (7%) patients tested positive for anti-PM/Scl antibodies. As presenting SSc manifestations, patients with anti-PM/Scl antibodies had higher prevalence of puffy fingers (11% versus 2%; p=0.002) and arthralgias (11% versus 4%; p=0.03), and lower prevalence of Raynaud’s phenomenon (65% versus 82%, p=0.002). Regarding cumulative manifestations, myositis (51% versus 15%; p<0.001), arthritis (43% versus 22%; p=0.001), and interstitial lung disease (ILD) (60% versus 45%, p=0.014) were more prevalent in patients with anti-PM/Scl antibodies. In fact, those patients with anti-Pm/Scl antibodies presented with FVC (77.4% ± 23.1% versus 85.8% ± 23,1%; p=0.006) and more severe ILD defined as FVC <70% (41% versus 24%; p=0.004). Death rate was similar in patients with and without PM/Scl antibodies (18% versus 17%; p=0.871).We did not find differences in terms of death rate nor in the causes of death (SSc and non-SSc related) according to the anti-PM/Scl antibodies profile.The 5- and 10-years survival rates of patients with anti-PM/Scl antibodies were 91% and 82% respectively, without differences with those without these antibodies (93% and 85%, respectively).Conclusion:In Spanish SSc patients, the presence of anti-PM/Scl antibodies confer a distinctive clinical profile. However, anti-PM/Scl antibodies do not play a role in the prognosis of these patients.References:[1]Stochmal A, Czuwara J, Trojanowska M, Rudnicka L. Antinuclear antibodies in systemic sclerosis: an update. Clin Rev Allergy Immunol 2020;58(1):40-51. doi: 10.1007/s12016-018-8718-8.Acknowledgments:We gratefully acknowledge all investigators who are part of the RESCLE Registry. We also thank the RESCLE Registry Coordinating Centre, S&H Medical Science Service, for their quality control data, logistic and administrative support and Prof. Salvador Ortiz, Universidad Autónoma de Madrid and Statistical Advisor S&H Medical Science Service for the statistical analysis of the data presented in this paper.Disclosure of InterestsNerea Iniesta-Arandia: None declared, Gerard Espinosa Speakers bureau: Glaxo-Smith-Kline, Janssen, Boehringer, Rovi, Alfredo Guillen del Castillo: None declared, Carles Tolosa Consultant of: Actelion pharmaceuticals, GSK, MSD., Gema Maria Lledó: None declared, Dolores Colunga Argüelles Consultant of: Actelion pharmaceuticals, GSK, MSD., Cristina González-Echávarri: None declared, Luis Sáez-Comet: None declared, Norberto Ortego: None declared, Jose Antonio Vargas-Hitos: None declared, Manuel Rubio-Rivas: None declared, Mayka Freire: None declared, Juan José Rios: None declared, Monica Rodriguez-Carballeira: None declared, Luis Trapiella Martínez: None declared, Vicent Fonollosa Pla Speakers bureau: Actelion, Carmen Pilar Simeón-Aznar Consultant of: Actelion pharmaceuticals, GSK, MSD., on behalf of RESCLE Investigators, Autoimmune Diseases Study Group (GEAS): None declared

AB0109 THE ROLE OF CD70 IN THE DEVELOPMENT OF RHEUMATOID ARTHRITIS

Background:Rheumatoid arthritis (RA) is a progressive, chronic inflammatory autoimmune disease. Pro-inflammatory molecules, activated lymphocytes, and the migration of inflammatory cells are important in the development of RA. There are many unknown causes of RA. And there are many patients who are refractory to treatment with known disease-modifying anti-rheumatic drugs. So, unknown cause of RA needs to be elucidated.CD70 is a member of the tumor necrosis factor (TNF) superfamily and a ligand for CD27. The interaction of CD70 with its receptor CD27 promotes expansion and differentiation of memory and effector T cells as well as B-cell expansion and plasma cell differentiation. Hypoxia is an important micro-environmental factor in RA synovium. Hypoxia induces activation of hypoxia inducible factor (HIF). The expression of HIF-2α is up-regulated in human RA synovium. Reactive oxygen species (ROS) has been implicated in the pathophysiology of RA.Objectives:In this study, we tried to examine the presence of CD70 in RA synovium and investigate the role of CD70 in the development of RA associated with HIF-2α and ROS.Methods:Fibroblast-like synoviocyte (FLS), peripheral blood (PB) and synovial fluid (SF) were used for experiments. FLS was stimulated with recombinant human (rh)-IL-17 and rh-TNF-α. N-acetyl-L-cysteine (NAC) was used as a ROS scavenger. HIF-2α inhibitor (PT-2385) was used for examine the effect of HIF-2α in RA-FLS. RT-PCR, qPCR, western blotting, flow-cytometry, ELISA, cell migration assay, and scratch wound assay were performed.Results:CD70 mRNA is present and elevated by stimulation with IL-17 and TNF-α in both RA-FLS and osteoarthritis (OA)-FLS (Fig 1). CD70 also expresses on the surface of RA-FLS and OA FLS (Fig 2). CD70 expression on the surface of FLS is elevated by stimulation with IL-17 and TNF-α in both RA and OA. Soluble CD27 is present higher in the supernatant of RA-SF than OA-SF (Fig 3). HIF-2α mRNA, HIF-2α protein, and the amount of ROS were all elevated after treatment with IL-17 and TNF-α in RA-FLS (Fig 4, Fig 5). CD70 expression and the amount of ROS were lowered by treatment with HIF-2α inhibitor in RA-FLS (Fig 6). Decreased amount of ROS results in decreased CD70 expression on the RA-FLS (Fig 7). CD70 influenced on cell migration directly or by HIF-2α (Fig 8).Conclusion:In this study, we found the function of CD70 in RA-FLS associated with HIF-2α and ROS. First, CD70 on RA-FLS interacts with CD27 in the RA-SF and this interaction produces sCD27 (Fig. 9) and CD70 has an influence on the migration of RA-FLS. Second, IL-17 and TNF-α are critical factors to trigger the expression of CD70, HIF-2α and ROS in RA synovium. Third, CD70 is regulated by HIF-2α associated with ROS. From these results, we suggest that CD70 may be a new therapeutic target of RA. And sCD27 also may be an important diagnostic maker of RA.References:[1]Lundy SK, Sarkar S, Tesmer LA, Fox DA. Cells of the synovium in rheumatoid arthritis. T lymphocytes. Arthritis Res Ther. 2007;9(1):202.[2]Nevius E, Gomes AC, Pereira JP. Inflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review. Clin Rev Allergy Immunol. 2016;51(1):59-78.[3]Bowman MR, Crimmins MA, Yetz-Aldape J, Kriz R, Kelleher K, Herrmann S. The cloning of CD70 and its identification as the ligand for CD27. J Immunol. 1994;152(4):1756-61.[4]Kitajima S, Lee KL, Fujioka M, Sun W, You J, Chia GS, et al. Hypoxia-inducible factor-2 alpha up-regulates CD70 under hypoxia and enhances anchorage-independent growth and aggressiveness in cancer cells. Oncotarget. 2018;9(27):19123-35.[5]Gaber T, Dziurla R, Tripmacher R, Burmester GR, Buttgereit F. Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do! Ann Rheum Dis. 2005;64(7):971-80.Disclosure of Interests:None declared

Stressor-induced modulation of immune function: a review of acute, chronic effects in animals

The present paper reviews recent studies on the effects of stress on immune function in laboratory animals. The emphasis is on those studies where a simultaneous comparison of acute and chronic stress regimens was determined, although additional relevant studies are also reviewed. The effects of stress on basic measurements of cellular and humoral immune measures are discussed, including the growing number of studies that have reported alterations in macrophage functions. The latter are key elements in the innate immune response, and like measurements of T cell function and antibody production, are inhibited and enhanced by stressor exposure. This review does not focus on the mechanisms by which stress alters immune function, there being little to add conceptually in terms of what was reported previously (see Kusnecov AW, Rabin BS, Int Arch Allergy Immunol 1994;105:107–121.). However, a question is raised in the conclusion as to how stressor effects on immune function should be interpreted, for it is clear that immunological processes in and of themselves elicit central nervous system responses that neurochemically and endocrinologically do not differ from those produced in response to psychological stressors. Therefore, at least in the short term stressor-induced immune changes may not necessarily reflect maladaptive adjustments, although, as demonstrated by some studies reviewed in this paper, they may pose a serious risk to health should stressor exposure be persistent and uncontrolled.