Sofie Lock Johansson1, Nassim Bazeghi Roberts2, Anders Schlosser1, Claus B Andersen3, Jørn Carlsen4, Helle Wulf-Johansson1, Susanne Gjørup Sækmose5, Ingrid L Titlestad6, Ida Tornoe1, Bruce Miller7, Ruth Tal-Singer7, Uffe Holmskov1, Jørgen Vestbo8, Grith Lykke Sorensen9. 1. Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark. 2. Respiratory Section, Hvidovre Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark. 3. Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark. 4. Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark. 5. Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark; Department of Clinical Immunology, Næstved Hospital, Ringstedgade 61, 4700 Næstved, Denmark. 6. Department of Respiratory Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. 7. GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. 8. Department of Respiratory Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; The University of Manchester, Manchester Academic Health Science Centre, 46 Grafton Street, M13 9NT Manchester, UK; 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. 9. Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark. Electronic address: glsorensen@health.sdu.dk.
Abstract
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.
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
Authors: Bartosz Pilecki; Anne T Holm; Anders Schlosser; Jesper B Moeller; Alexander P Wohl; Alexandra V Zuk; Stefanie E Heumüller; Russell Wallis; Soren K Moestrup; Gerhard Sengle; Uffe Holmskov; Grith L Sorensen Journal: J Biol Chem Date: 2015-11-24 Impact factor: 5.157
Authors: Lisa E Dorn; William Lawrence; Jennifer M Petrosino; Xianyao Xu; Thomas J Hund; Bryan A Whitson; Matthew S Stratton; Paul M L Janssen; Peter J Mohler; Anders Schlosser; Grith L Sorensen; Federica Accornero Journal: Circ Res Date: 2021-02-03 Impact factor: 17.367
Authors: Ting Xue; Ping Liu; Yong Zhou; Kun Liu; Li Yang; Robert L Moritz; Wei Yan; Lisa X Xu Journal: Theranostics Date: 2016-03-21 Impact factor: 11.556
Authors: Qiuying Chen; Ruba S Deeb; Yuliang Ma; Michelle R Staudt; Ronald G Crystal; Steven S Gross Journal: PLoS One Date: 2015-12-16 Impact factor: 3.240
Authors: Thilo Bracht; Christian Mölleken; Maike Ahrens; Gereon Poschmann; Anders Schlosser; Martin Eisenacher; Kai Stühler; Helmut E Meyer; Wolff H Schmiegel; Uffe Holmskov; Grith L Sorensen; Barbara Sitek Journal: J Transl Med Date: 2016-07-04 Impact factor: 5.531