OP0096 CAN IMMUNOGLOBULINS G FROM SYSTEMIC SCLEROSIS PATIENTS INFLUENCE THE SECRETOME OF DERMAL FIBROBLASTS?

Background Autoantibodies (Aab) are frequent in systemic sclerosis (SSc) [1]. Recently, it has been showed that immunoglobulins G (IgG) from SSc promoted proinflammatory and profibrotic phenotype monocyte secretome [2]. Fibroblasts (FB) key effectors cells data on FB proteins secretion the presence of IgG patients lacking. While recognized as potent biomarkers, pathogenic role Aab is much more debated. Objectives To explore purified Methods Normal dermal were cultured with diffuse cutaneous (dcSSc), limited (lcSSc) or healthy controls (HC). After 72 h culture, cell supernatants collected, centrifuged passed through a filter to remove cells. digestion, was explored using mass spectrometry coupled liquid chromatography (LC-MS/MS). Analysis variance (ANOVA) hierarchical clustering used identify responses patterns. Results Proteomic identified quantified 1268 proteins, among them 377 significant after ANOVA. HC appeared distinct. Hierarchical ANOVA 3 distinct groups secretome: first group including mostly dcSSc anti-topoisomerase-I (ATA) positive (dcSSc ATA+) patients, second ATA negative ATA-) third heterogeneous majority HC, lcSSc anti-centromere (lcSSc ACA+) ATA- (Figure 1. A ). The comparison ATA+ vs revealed 203 differentially expressed (DEP) B enriched Gene Ontology (GO) terms upregulated involved endocytic vesicle lumen, extracellular matrix glycosaminoglycan binding. comparisons ACA+ 85 15 DEP, respectively. Follistatin, amyloid beta A4 protein, myosin-9 calreticulin commonly overexpressed subtypes SSc. 40 exclusively condition ATA+. Among them, collagen alpha-1(VII) chain, galectin-3-binding desintegrin metalloproteinase domain-containing 10, low affinity immunoglobulin gamma Fc region receptor III-A, CD59 glycoprotein, growth arrest-arrest specific protein clusterin C Figure Heatmap representing all samples. Cluster analysis 2 different clusters expression (A). Volcanoplot represented (B). Venn diagram common exclusive following comparison: (C). HC: controls; ATA+: patients; ATA-: ACA+: patients. ANOVA: variance. Conclusion Using sensitive proteomic approach, we modified serotype dependent manner. support References [1]Denton CP, Khanna D. Systemic sclerosis. Lancet 2017; 390:1685 –99. doi:10.1016/S0140-6736(17)30933-9 [2]Murthy S, Wannick M, Eleftheriadis G, et al. Immunoglobulin programs pro-inflammatory monocyte-like THP-1 Rheumatology (Oxford ) 2021; 60:3012 –22. doi:10.1093/rheumatology/keaa747 Disclosure Interests None declared.