Microfibrillar-associated protein 4: A potential biomarker of chronic obstructive pulmonary disease - 10/07/14

Doi : 10.1016/j.rmed.2014.06.003

Sofie Lock Johansson ^a, Nassim Bazeghi Roberts ^b, Anders Schlosser ^a, Claus B. Andersen ^c, Jørn Carlsen ^d, Helle Wulf-Johansson ^a, Susanne Gjørup Sækmose ^a,^e, Ingrid L. Titlestad ^f, Ida Tornoe ^a, Bruce Miller ^g, Ruth Tal-Singer ^g, Uffe Holmskov ^a, Jørgen Vestbo ^f,^h,ⁱ, Grith Lykke Sorensen ^a,^⁎
^a Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark
^b Respiratory Section, Hvidovre Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark
^c Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark
^d Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark
^e Department of Clinical Immunology, Næstved Hospital, Ringstedgade 61, 4700 Næstved, Denmark
^f Department of Respiratory Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark
^g GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA
^h The University of Manchester, Manchester Academic Health Science Centre, 46 Grafton Street, M13 9NT Manchester, UK
ⁱ University Hospital South Manchester NHS Foundation Trust, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester, Greater Manchester M23 9LT, UK

^∗Corresponding author. Tel.: +45 6550 3932.

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Summary

Background

Microfibrillar-associated protein 4 (MFAP4) is a matricellular glycoprotein that co-localises with elastic fibres and is highly expressed in the lungs. The aim of this study was to test the hypothesis that plasma MFAP4 (pMFAP4) reflects clinical outcomes in chronic obstructive pulmonary disease (COPD).

Methods

pMFAP4 was measured by an AlphaLISA immunoassay in stable COPD (n = 69) at baseline and at follow-up until 24 months after inclusion and in acute exacerbations of COPD (AECOPD) (n = 14) at baseline and until 6 months after inclusion.

Results

The majority of patients (89%) were in GOLD II and III. Multiple linear regressions showed positive associations between pMFAP4 and the Global initiative for Obstructive Lung Disease (GOLD) grade (p = 0.01), modified Medical Research Council score (p < 0.0001) and BODE index (p = 0.04). Negative associations were found with 6-min walking distance (p = 0.04) and bronchodilator-induced reversibility (p = 0.02). The pMFAP4 levels varied less than 25% between the baseline and a 3 month follow-up in 83% of the patients. The pMFAP4 levels appeared unaffected in the acute phase of severe AECOPD but rose to an increased stable level within one month after hospitalization.

Conclusion

Increased pMFAP4 was associated to the severity in COPD and has the potential to serve as a stable disease biomarker. This observation warrants confirmation in a larger longitudinal COPD population.

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Keywords : Microfibrillar-associated protein 4, Biomarkers, Chronic obstructive pulmonary disease, Acute exacerbation of COPD, BODE index, Modified Medical Research Council score