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

• Published in: The European respiratory journal Vol. 43; no. 5; pp. 1430 - 1438
• Main Authors: Chien, Jason W., Richards, Thomas J., Gibson, Kevin F., Zhang, Yingze, Lindell, Kathleen O., Shao, Lixin, Lyman, Susan K., Adamkewicz, Joanne I., Smith, Victoria, Kaminski, Naftali, O’Riordan, Thomas
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.05.2014
• Subjects: Aged; Amino Acid Oxidoreductases - blood; Biological and medical sciences; Biomarkers - blood; Carbon Monoxide - chemistry; Cohort Studies; Disease Progression; Female; Humans; Idiopathic Pulmonary Fibrosis - blood; Idiopathic Pulmonary Fibrosis - physiopathology; Immunoassay; Male; Medical sciences; Middle Aged; Pneumology; Regression Analysis; Respiratory system : syndromes and miscellaneous diseases; Risk Factors; Lung disease; Pulmonary fibrosis; Prognosis; Enzyme; Respiratory disease; Clinical biology; Idiopathic; Oxidase; Evolution; Oxidoreductases
• ISSN: 0903-1936; 1399-3003; 1399-3003
• DOI: 10.1183/09031936.00141013

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.