Microfibrillar-associated protein 4 in serum is associated with asthma in Danish adolescents and young adults

Benjamin Hoffmann-Petersen*, Raymond Suffolk, Jens Jakob Herrche Petersen, Thomas Houmann Petersen, Kirsten Arendt, Arne Høst, Susanne Halken, Grith Lykke Sorensen, Lone Agertoft

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
JournalImmunity, Inflammation and Disease
Volume7
Issue number3
Pages (from-to)150-159
ISSN2050-4527
DOIs
Publication statusPublished - Sep 2019

Fingerprint

Young Adult
Serum
microfibrillar protein
Nitric Oxide
Confidence Intervals
Extracellular Matrix Proteins
Denmark
Ambulatory Care Facilities
Prospective Studies
Pediatrics
Lung

Keywords

  • adolescent
  • asthma
  • biomarkers
  • child
  • microfibrillar-associated protein 4

Cite this

@article{62b7e31d4f8c48cdb54108cdea3e3c19,
title = "Microfibrillar-associated protein 4 in serum is associated with asthma in Danish adolescents and young adults",
abstract = "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.",
keywords = "adolescent, asthma, biomarkers, child, microfibrillar-associated protein 4",
author = "Benjamin Hoffmann-Petersen and Raymond Suffolk and Petersen, {Jens Jakob Herrche} and Petersen, {Thomas Houmann} and Kirsten Arendt and Arne H{\o}st and Susanne Halken and Sorensen, {Grith Lykke} and Lone Agertoft",
note = "{\circledC} 2019 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.",
year = "2019",
month = "9",
doi = "10.1002/iid3.254",
language = "English",
volume = "7",
pages = "150--159",
journal = "Immunity, Inflammation and Disease",
issn = "2050-4527",
publisher = "JohnWiley & Sons Ltd.",
number = "3",

}

Microfibrillar-associated protein 4 in serum is associated with asthma in Danish adolescents and young adults. / Hoffmann-Petersen, Benjamin; Suffolk, Raymond; Petersen, Jens Jakob Herrche; Petersen, Thomas Houmann; Arendt, Kirsten; Høst, Arne; Halken, Susanne; Sorensen, Grith Lykke; Agertoft, Lone.

In: Immunity, Inflammation and Disease, Vol. 7, No. 3, 09.2019, p. 150-159.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Microfibrillar-associated protein 4 in serum is associated with asthma in Danish adolescents and young adults

AU - Hoffmann-Petersen, Benjamin

AU - Suffolk, Raymond

AU - Petersen, Jens Jakob Herrche

AU - Petersen, Thomas Houmann

AU - Arendt, Kirsten

AU - Høst, Arne

AU - Halken, Susanne

AU - Sorensen, Grith Lykke

AU - Agertoft, Lone

N1 - © 2019 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

KW - adolescent

KW - asthma

KW - biomarkers

KW - child

KW - microfibrillar-associated protein 4

U2 - 10.1002/iid3.254

DO - 10.1002/iid3.254

M3 - Journal article

VL - 7

SP - 150

EP - 159

JO - Immunity, Inflammation and Disease

JF - Immunity, Inflammation and Disease

SN - 2050-4527

IS - 3

ER -