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

Abstract

BackgroundAutoantibodies (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].ObjectivesWe aim to identify new ab targets and ab discriminating healthy controls (HC) from SSc patients or SSc clinical phenotypes, organ involvements and therapy.MethodsSerum 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.ResultsIn 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.Figure 1.Different univariate correlations between abs in HC and SSc. The correlations of the ab concentrations are generally increased in SSc compared to HC. Largest accumulated differences are found for ETAR, VEGFA, AT1R and EGFR as indicated by the covered degrees in the circle. Dark bands depict significant differences after FDR-correction (p<.05)ConclusionSSc 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.