AB0177 Increased levels of the inflammatory proteins CXCL10, CXCL11, TNFR2 and YLK-40 typify the earliest phase of systemic sclerosis (SSC)

• Published in: Annals of the rheumatic diseases Vol. 76; no. Suppl 2; p. 1108
• Main Authors: Cossu, M, Bon, L van, Rossato, M, Beretta, L, Radstake, TRDJ
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2017
• Subjects: Angiopoietin; Arthritis; Biomarkers; CXCL10 protein; CXCL11 protein; Fibrosis; Inflammation; IP-10 protein; Replication; Rheumatology; Scleroderma; Skin; Systemic sclerosis
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2017-eular.5295

BackgroundDefinite systemic sclerosis (defSSc) patients yet lacking the prototypical signs of fibrosis stratify in an intermediate severity stage between pre-clinical and fibrotic, limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) phenotypical subsets1.ObjectivesWe aimed to molecularly position defSSc patients in respect to healthy controls (HC) and early SSc (EaSSc) patients with a broad panel of serum mediators of inflammation and tissue damage in an attempt to increase the knowledge in pathophysiologic mechanisms and biomarkers availability, thereby offering new ground for disease interception before fibrosis develops.MethodsTo this end, an 88-plex immunoassay was performed in sera from an identification cohort composed of 21 EaSSc according to LeRoy and Medsger criteria2 without other signs and symptoms of evolutive disease, 15 defSSc patients according to the 2013 ACR/EULAR criteria3 without skin or lung fibrosis and 11 HC. A larger cohort comprising 47 EaSSc, 48 defSSc and 43 HC was used for replication purposes. Fifty-one lcSSc and 35 dcSSc as comparison with established, fibrotic disease were recruited in parallel.ResultsSixteen mediators differentially expressed in EaSSc and defSSc were selected for replication (one-way ANOVA and/or ANOVA polynomial test for trend with exploratory threshold p<0.1). Amongst these, after correction for multiple comparisons, CXCL10/IP-10, CXCL11/I-TAC, TNFR2 and CHI3L1/YKL-40 showed a significant upregulation in defSSc and EaSSc with a linear increase from HC to EaSSc to defSSc. The level of upregulation observed in defSSc individuals was similar (CXCL10/IP-10, CXCL11/I-TAC) or further increased (TNFR2, CHI3L1/YKL-40) in lcSSc and dcSSc patients. A set of 7 ranked markers (Angiopoietin-2, TNFR2, CXCL11/I-TAC, CXCL10/IP-10, sICAM-1, CHI3L1/YKL-40, CXCL9/MIG) provided a good visualization of the gradually increasing pattern from HC to EaSSc to defSSc to lcSSc and dcSSc.ConclusionsThis is the first attempt to validate circulating biomarkers defining the earliest phases of SSc. Despite the need for confirmation in a prospective setting, our results confirm that defSSc might represent an intermediate entity between pre-clinical stages and the most severe subsets of disease, thereby opening new perspectives on SSc pathophysiology and disease interception.References Cossu M, et al. Rheumatology 2016.LeRoy EC, et al. J Rheumatol 2001.van den Hoogen F, et al. Arthritis Rheum 2013. AcknowledgementsSupported by a grant from Gruppo Italiano per la Lotta alla Sclerodermia (GILS). MC and TR are partly supported by the VIDI laureate and Dutch Arthritis Foundation (NWO, Netherlands Institute for Science) and ERC starting grant (EU) obtained by TR. The LTI MultiPlex Core Facility is acknowledged for technical performance of the multiplex immune assays.Disclosure of InterestNone declared