title: 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.
authors.affiliation: Inc., Seattle, WA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Chien
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Richards
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Gibson
authors.forename: Yingze
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kathleen O
authors.initials: KO
authors.lastname: Lindell
authors.forename: Lixin
authors.initials: L
authors.lastname: Shao
authors.forename: Susan K
authors.initials: SK
authors.lastname: Lyman
authors.forename: Joanne I
authors.initials: JI
authors.lastname: Adamkewicz
authors.forename: Victoria
authors.initials: V
authors.lastname: Smith
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Riordan
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000594:Amino Acid Oxidoreductases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002248:Carbon Monoxide / Q000737:chemistry; D015331:Cohort Studies; D018450:Disease Progression; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000503:physiopathology; D007118:Immunoassay; D012044:Regression Analysis; D012307:Risk Factors; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D064887:Observational Studies as Topic
chemical_list: D000594:Amino Acid Oxidoreductases; D015415:Biomarkers; D002248:Carbon Monoxide; C119091:LOXL2 protein, human