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Microfibrillar-associated protein 4 in serum is associated with asthma in Danish adolescents and young adults
Benjamin Hoffmann-Petersen1,2,3, Raymond Suffolk4, Jens Jakob Herrche Petersen5
1Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Background:
Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related protein superfamily, which plays multifaceted roles in innate immunity and normal endothelial function. It has been proposed that MFAP4 promotes the development of asthma in vivo and proasthmatic pathways of bronchial smooth muscle cells in vitro. The aim of this study was to investigate the significance of serum MFAP4 in adolescents and young adolescents with persistent asthma.
Methods:
Prospective, observational study including adolescents and young adults (age 11-27 years) previously diagnosed with asthma during childhood 2003 to 2005 (0-15 years) at the four pediatric outpatient clinics in the Region of Southern Denmark (n = 449). Healthy controls were recruited at follow-up (n = 314). Detection of serum MFAP4 was performed by AlphaLISA technique.
Results:
Current asthma was associated to a 14% higher mean level of serum MFAP4 compared with controls (expβ 1.14, 95% confidence intervals [CI], 1.05-1.23) and a 6% higher mean level compared with subjects with no current asthma (expβ 1.06, 95% CI, 0.99-1.13). No association was found at follow-up between serum MFAP4 and self-reported atopic symptoms (other than asthma), Asthma Control Test-score, fractional exhaled nitric oxide (FeNO), nor to flow rate at 1 second, forced vital capacity, and forced expiratory flow 25% to 75%, response to short-acting beta 2 agonist or mannitol.
Conclusions:
We found a significantly higher mean level of serum MFAP4 in adolescent and young adults with mild to moderate asthma compared with healthy controls but no association to FeNO and lung function nor to the response to short-acting beta 2 agonist or mannitol. The result supports the hypothesis that MFAP4 plays a role in the pathogenesis of asthma although the marker did not demonstrate any obvious potential as an asthma biomarker in adolescents and young adults with asthma. To understand the possible proasthmatic functions of MFAP4, further investigation in specific asthma phenotypes and the underlying molecular mechanisms is warranted.
Insights
Serum microfibrillar-associated protein 4 (MFAP4) levels are higher in adolescents with asthma. While MFAP4 may play a role in asthma pathogenesis, it shows limited potential as a biomarker in this age group.
Area of Science:
- Immunology
- Pulmonology
- Biochemistry
Background:
- Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein implicated in innate immunity and endothelial function.
- MFAP4 has been proposed to contribute to asthma development and pro-asthmatic pathways in bronchial smooth muscle cells.
Purpose of the Study:
- To investigate the clinical significance of serum MFAP4 levels in adolescents and young adults diagnosed with persistent asthma.
Main Methods:
- A prospective, observational study included 449 adolescents and young adults with childhood-diagnosed asthma and 314 healthy controls.
- Serum MFAP4 levels were quantified using the AlphaLISA technique.
Main Results:
- Adolescents with current asthma exhibited a 14% higher mean serum MFAP4 level compared to healthy controls.
- No significant association was found between serum MFAP4 levels and asthma control, lung function, or airway hyperresponsiveness.
Conclusions:
- Elevated serum MFAP4 levels were observed in adolescents with mild to moderate asthma, suggesting a potential role in asthma pathogenesis.
- MFAP4 did not demonstrate significant potential as a diagnostic biomarker for asthma in this population, warranting further research into specific asthma phenotypes and molecular mechanisms.
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