Utility of serum biomarkers to detect ILD in idiopathic pulmonary fibrosis (IPF) and scleroderma-associated ILD (SSc-ILD).

Abstract

Introduction: Accurate prediction of disease progression and therapeutic response in interstitial lung disease (ILD) is lacking. Validation of candidate serum biomarkers remains limited by small, single-centre studies without longitudinal disease measures. We assessed the diagnostic role of 28 biomarkers in two large, multicentre cohorts of Australian idiopathic pulmonary fibrosis (IPF) and scleroderma-ILD (SSc-ILD) patients with prospective longitudinal data and linked sera. Method(s): The serum concentration of 28 biomarkers was evaluated using bead-based multiplex assays (SP-D, MMP-1/-3/-7/-12, periostin, CXCL13, CCL2, IL-6/-8, CXCL4/-10/-12, TGF-beta, Ca15.3, Endothelin 1, VEGF, Amphiregulin, TIMP1, CCL18, ICAM, VCAM, E-selectin) and ELISA (KL-6, fibulin-1, LOXL2). IPF and SSc patients were identified from the Australian IPF Registry and Scleroderma Cohort Study, including prospective, longitudinal clinical and outcome data and linked serum biobanks. Sera was also obtained from non-smoking healthy controls. Result(s): 640 patients (mean age 60 +/- 13.7 years, 33% male, 52% ever smokers), including 172 IPF, 168 SSc, 270 SSc-ILD patients and 30 healthy controls were analysed. IPF patients were older (mean 70 +/- 18 years) and more male predominant (70% male). SSc-ILD patients were less likely to be ever smokers (44%). FVC did not differ between groups (mean 2.68 +/- 0.80L, 76 +/- 12%pred). DLCO was lower in IPF patients versus SSc and SSc-ILD (mean 38, 64 and 58% respectively; P <0.001) and SSc-ILD compared with SSc (P = 0.003). Conclusion(s): We identified a panel of serum proteins able distinguish IPF and SSc-ILD from non-ILD patients; between ILD subtypes; and SSc with and without ILD. Further analysis is required to determine the relationship of biomarkers with disease severity and outcomes.