Basic (PS01–PS58)

Rheumatology 2012;51:ii27–ii123 POSTER SESSION BASIC (PS01–PS58) PS01. SERUM AND SPUTUM CAVEOLIN-1, TGF-b AND ET-1 LEVELS IN SCLERODERMA PATIENTS N. Yilmaz1, S. Olgun2, R. Ahiskali3, S. Karakurt2 and S. Yavuz1 1 Department of Rheumatology, 2Department of Chest Medicine and 3 Department of Pathology, Marmara University, Faculty of Medicine, Istanbul, Turkey Aim. Scleroderma (SSc) is a connective tissue disease characterized by diffuse endothelial damage and interstitial fibrosis. Despite the pathogenesis of SSc is unknown, some studies implied the role of caveolin-1 (Cav-1), TGF-b and ET-1 in interstitial fibrosis and vasculopathy. The aim was evaluate a non-invasive marker to determine interstitial lung involvement and its progression in the SSc patients. Methods. he study population consisted of 55 SScs, 25 asthma patients and 16 healthy volunteers (HCs). All SSc patients were evaluated in every 6 months for clinical and laboratory parameters. ILD diagnosis and progression were determined pulmonary function tests and high-resolution CT. Serum and sputum Cav-1, TGF-b and ET-1 levels were measured by ELISA technique for all patients and controls. Results. The mean (S.D.) age was 48 (25–72 years) years and the mean disease duration was 5 (1–29 years) years in SSc patients. Fortyfive (81.8%) patients had interstitial lung disease, 8 (14.5%) had pulmonary hypertension and 22 (40%) had digital ulcer. The mean disease activity score was 5.4 (2.6). Forty-five (81.8%) patients were taking immunsppuressive treatment and seven (12.7%) patients were taking endothelin receptor antagonist treatment. Serum Cav-1 levels were lower in SSc and asthma patients compared with HC [SSc 0.29 (0.11), asthma 0.27 (0.07) vs HC 0.39 (0.1) ng/ml] (P < 0.01).On the other hand sputum Cav-1 levels were lower in SSc patients compared with both groups [SSc 0.19 (0.04) vs asthma 0.24 (0.07), HC 0.28 (0.07) ng/ml] (P < 0.001). Although, there was no difference for serum TGF-b levels among the groups {SSc [8176 (4298)], asthma [7979 (4055)] and HC [8497 (3574 pg/ml)]}, the mean sputum TGF-b was significantly higher in the asthma patients compared with the other groups {Asthma [156.8 (147.5)] vs SSc [85.6 (85.6)] and HC [89.5 (83.7 pg/ml)]} (P < 0.05).Only mean serum ET-1 was significantly higher in the SSc patients compared with control groups {SSc [3.43 (6.05)] vs asthma [0.73 (0.53)] and HC [0.58 (0.29) fmol/ml)]} (P < 0.01). Neither serum or sputum Cav-1 abnormality nor TGF-b or ET-1 levels correlated with disease activity, disease subsets, pulmonary hypertension and presence of digital ulcer or interstitial lung disease. No association was observed between alveolitis index, fibrosis index, total skor and Cav-1, ET-1 ve TGF-b serum and Cav-1, ET-1 sputum levels (P > 0.05). Only sputum TGF-b levels positively correlated with alveolitis index (r ¼ 0.34) and inversely correlated with FVC measurements (r: ¼ 0.44, P < 0.05). In SSc patients, Cav-1 levels decreased significantly in serum samples at 0, 6 and 12 months, whereas fibrosis score increased at chest CT scan at follow-up. Conclusion. These results suggest that Cav-1 plays a role in the pathogenesis of the SSc and sputum TGF-b levels may be used as a marker for severity of interstitial lung involvement. PS02. Th 17 CELLS ARE INCREASED IN THE SKIN OF SSc INDIVIDUALS M. Truchetet1, E. Raschi2, C. Lubatti3, L. Fontao4, P. Meroni2,3 and C. Chizzolini1 1 University Hospital – Immunology and Allergy, Geneva, Switzerland, 2 IRCCS – Istituto Auxologico Italiano, 3Istituto Gaetano Pini – Rheumatology, Milan, Italy and 4University Hospital – Dermatology, Geneva, Switzerland Background. In SSc inappropriate T-cell responses are thought to participate in initiating events ultimately leading to excessive extracellular matrix deposition and fibrosis. The recently described Th 17 subset has been shown to be increased in the peripheral blood of SSc individuals. The aim of our study was to assess the presence of Th17 cells in the SSc and healthy skin. Material and methods. Upon informed consent and approval by the ethical committee, skin samples were obtained from eight SSc and eight healthy donors used as controls (ctrl). T-cell lines from the skin of all the individuals were grown in the presence of IL-2, each in four independent replicates. Intracellular localization of IL-17A, IL-22, IL-4 and IFN-g in CD4þ T cells as well as the surface expression of chemokine receptors were assessed by multiparametric FACS analysis. Paraffin embedded skin biopsies were stained for CD3/IL17 or a-smooth muscle actin/IL-17 and positive cells frequency determined by laser scanning confocal microscopy. Results. In T-cell lines generated from the skin 79.1% (10.5) and 73.7% (16.9) were CD4þ T cells in SSc and ctrl, respectively. Production of IL-17A, IL-22, IL-4 and IFN-g was detected in all T-cell lines. Statistically significant differences were observed in the subsets co-producing IL-17A and IL-22 [5.6% (7.9) vs 2.5 (1.6)] as well as IFN-g and IL-4 [7.8% (4.6) vs 2.4% (1.8)], which were more frequent in SSc compared with ctrl. As expected, T-cell lines generated from the skins were skewed for high expression of CCR4 compared with counterparts from the peripheral blood. In addition, the percentage of CXCR3þ cells was higher in SSc [48.1% (17.9] compared with ctrl [29.5% (13.0)]. Finally, histological identification of CD3þIL-17þ cells was possible in both SSc and ctrl skin, and Th17 cells were more frequent in SSc (3.5 cells/field) than ctrl (1.7 cells/field) (P ¼ 0.05). Furthermore, myofibroblasts were only found in SSc samples and always in proximity with IL-17 positive cells. Conclusions. Our preliminary data indicate that Th17 co-producing IL-17A and IL-22 are increased in SSc skin, which may suggest a role for these cells in the pathogenesis of the disease, particularly since myofibroblasts were preferentially located in proximity of IL-17 positive cells. These results provide new rationale for targeting IL-17 and the Th17 differentiation pathway as novel approaches to harness the clinical course of SSc. PS03. S100A4 IS A NOVEL MEDIATOR OF TGF-b DRIVEN FIBROBLASTS ACTIVATION AND DERMAL FIBROSIS IN SSc M. Tomcik1, K. Palumbo2, P. Zerr2, B. G. Fuernrohr2, J. Avouac3, A. Horn2, C. Dees2, A. Akhmetshina2, C. Beyer2, L. Andres Cerezo1, R. Becvar1, O. Distler4, M. Grigorian5, L. Senolt1, G. Schett2 and J. H. W. Distler2 1 Department of Clinical and Experimental Rheumatology, Institute of Rheumatology, 1st Faculty of Medicine, Charles Univ, Prague, Czech Republic, 2Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, 3Rheumatology A Department, Paris Descartes University, Cochin Hospital, Paris, France, 4Experimental Rheumatology and Zurich Center of Integrative Human Physiology, University Hospital, Zurich, Switzerland and 5Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark Backgrou (...truncated)