Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression

Abstract

We evaluated whether lysyl oxidase-like 2 (LOXL2), which promotes cross-linking of collagen in pathological stroma, was detectable in serum from idiopathic pulmonary fibrosis (IPF) patients, and assessed its relationship with IPF disease progression. Patients from the ARTEMIS-IPF (n=69) and the Genomic and Proteomic Analysis of Disease Progression in IPF (GAP) (n=104) studies were analysed. Baseline serum LOXL2 (sLOXL2) levels were compared with baseline clinical and physiological surrogates of disease severity, and the association with IPF disease progression was assessed using a classification and regression tree (CART) method. sLOXL2 correlated weakly with forced vital capacity and carbon monoxide diffusion capacity (r -0.24-0.05) in both cohorts. CART-determined thresholds were similar: ARTEMIS-IPF 800 pg·mL(-1) and GAP 700 pg·mL(-1). In ARTEMIS-IPF, higher sLOXL2 (>800 pg·mL(-1)) was associated with increased risk for disease progression (hazard ratio (HR) 5.41, 95% CI 1.65-17.73). Among GAP subjects with baseline spirometric data (n=70), higher sLOXL2 levels (>700 pg·mL(-1)) were associated with more disease progression events (HR 1.78, 95% CI 1.01-3.11). Among all GAP subjects, higher sLOXL2 levels were associated with increased risk for mortality (HR 2.28, 95% CI 1.18-4.38). These results suggest that higher sLOXL2 levels are associated with increased risk for IPF disease progression. However, due to multiple limitations, these results require validation.