POS0150 AUTOANTIBODIES AGAINST FIBROBLAST GROWTH FACTOR (FGF-2), PLACENTAL GROWTH FACTOR (PLGF) AND BETA-ADRENERGIC RECEPTOR 1 (ADRB1) IN AN ALTERED NETWORK OF AUTOANTIBODIES IN SYSTEMIC SCLEROSIS

Susanne Schinke , Kirstin N. Sterner , Harald Heidecke , Hauke Busch , Axel Kuenstner , Inke R. König , C. J. K. Fouodo , Ulrich Müller , S. Comduehr , Tanja Lange , F. Lübber , Frederique Paulus , H. Grasshoff , Gabriela Riemekasten ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1136/annrheumdis-2023-eular.3895

Background Autoantibodies (ab) against G protein-coupled receptors (GPCR), such as ab against angiotensin II receptor type 1 (AT1R), endothelin receptor type A (ETAR) or CXC chemokine receptor 3 and 4 (CXCR3/4) may contribute to the pathogenesis of systemic sclerosis (SSc) [1]. AT1R- and ETAR-ab are associated with SSc-related mortality and CXCR3/4- ab predict a deteriorating pulmonary fibrosis [2,3]. Objectives We aim to identify new ab targets and ab discriminating healthy controls (HC) from SSc patients or SSc clinical phenotypes, organ involvements and therapy. Methods Serum ab levels against a panel of GPCR, GF and GFR were measured by ELISA in SSc (n=177) and compared to HC (n=88). Gender matched and age adjusted data were screened for univariate differences of ab levels in clinical phenotypes, explored for multivariate predictive performance of ab levels by a random-forest classifier and tested for differences of ab correlations. Results In SSc ab levels against 19 targets were higher compared to HC. Abs against fibroblast growth factor-2 (FGF-2), beta-adrenergic receptor 1 (ADRB1), and placental growth factor (PIGF) discriminated best SSc patients from HC. Multivariate predictions supported the ranking value of FGF-2 and ADRB1-abs for SSc and abs against ADRB1/2, muscarinic receptor 1 (M1R) and alpha-adrenergic receptor 2 ADRA2 for diffuse cutaneous SSc (dSSc) versus limited cutaneous SSc (lSSc). Ab levels were denser and stronger correlated in SSc than in HC (figure 1), suggesting a disturbed regulation of ab with a prominent role of FGF-2-abs in SSc. Comparing dSSc to lSSc, dSSc showed higher ab levels and correlated with several disease characteristics, but the multivariate classification showed poor accuracy. Conclusion SSc is characterized by both quantitative and qualitative alterations in ab levels and ab correlations. This study reveals ab against FGF-2, ADRB1 and PIGF to be new biomarkers of SSc. Alterations within these ab correlation networks could help to identify pathways promoting SSc and its clinical manifestations. References [1]Cabral-Marques O et al. 2018. GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis Nature Communications9 5224 [2]Riemekasten G et al. 2011. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis Annals of the Rheumatic Diseases70 530–6 [3]Weigold F et al. Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis. Arthritis Res Ther20, 52 Acknowledgements We thank G. Marschner for excellent technical assistance and Prof Goerg and his team from UKSH Campus Lübeck, bloodbank, for helping to acquire healthy blood donors. Disclosure of Interests Susanne Schinke Grant/research support from: Abbvie, Kristina Sterner: None declared, Harald Heidecke Shareholder of: Celltrend Company, Hauke Busch: None declared, Axel Kuenstner: None declared, Imke König: None declared, Césaire J. K. Fouodo: None declared, Antje Müller: None declared, Sara Comduehr: None declared, Tanja Lange: None declared, Finn Lübber: None declared, Frieder Paulus: None declared, Hanna Grasshoff: None declared, Gabriela Riemekasten: None declared.