Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.
BACKGROUND
The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF.


METHODS
Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry.


RESULTS
Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = -0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012).


CONCLUSIONS
Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments.
The Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia; Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, and Royal Prince Alfred Hospital (Sydney Local Health District), Sydney, NSW, Australia. Electronic address: jade.jaffar@sydney.edu.au.
Jade
J
Jaffar
The Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia.
Sofia
S
Unger
Sydney Medical School, The University of Sydney, and Royal Prince Alfred Hospital (Sydney Local Health District), Sydney, NSW, Australia.
Tamera J
TJ
Corte
Sydney Medical School, The University of Sydney, and Royal Prince Alfred Hospital (Sydney Local Health District), Sydney, NSW, Australia.
Michael
M
Keller
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA.
Paul J
PJ
Wolters
Department of Respiratory Diseases, University Hospital of Modena, University of Modena and Reggio Emilia, Modena, Italy; Department of Interstitial Lung Disease, University of Southampton, Southampton, England.
Luca
L
Richeldi
Department of Respiratory Diseases, University Hospital of Modena, University of Modena and Reggio Emilia, Modena, Italy.
Stefania
S
Cerri
Lung Institute of Western Australia, Centre for Asthma Allergy and Respiratory Research, The University of Western Australia, Perth, WA, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Western Australian Institute for Medical Research, Perth, WA, Australia.
Cecilia M
CM
Prêle
Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle and Hunter Medical Research Institute (HMRI), New Lambton Heights, NSW, Australia.
Philip M
PM
Hansbro
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC.
William Scott
WS
Argraves
Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, University of New South Wales, Randwick, NSW, Australia.
Rema A
RA
Oliver
The Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia; School of Medical and Molecular Biosciences, The University of Technology Sydney, Sydney, NSW, Australia.
Brian G
BG
Oliver
The Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia; Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia.
Judith L
JL
Black
The Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia; Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, and Royal Prince Alfred Hospital (Sydney Local Health District), Sydney, NSW, Australia.
Janette K
JK
Burgess
D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018929:Cell Culture Techniques; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism*; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D008875:Middle Aged; D014481:United States
D015415:Biomarkers; D002135:Calcium-Binding Proteins; C060820:fibulin