Microfibrillar-associated protein 4: a potential biomarker of chronic obstructive pulmonary disease

Respir Med. 2014 Sep;108(9):1336-44. doi: 10.1016/j.rmed.2014.06.003. Epub 2014 Jun 20.


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.

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

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Carrier Proteins / blood*
  • Carrier Proteins / metabolism
  • Case-Control Studies
  • Extracellular Matrix Proteins / blood*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume / physiology
  • Glycoproteins / blood*
  • Glycoproteins / metabolism
  • Humans
  • Lung / metabolism
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Severity of Illness Index
  • Vital Capacity / physiology


  • Biomarkers
  • Carrier Proteins
  • Extracellular Matrix Proteins
  • Glycoproteins
  • MFAP4 protein, human