Does urinary peptide content differ between COPD patients with and without inherited alpha-1 antitrypsin deficiency?

Carleo, A., Chorostowska-Wynimko, J., Koeck, T., Mischak, H., Czajkowska-Malinowska, M., Rozy, A., Welte, T. and Janciauskiene, S. (2017) Does urinary peptide content differ between COPD patients with and without inherited alpha-1 antitrypsin deficiency? International Journal of Chronic Obstructive Pulmonary Disease, 12, pp. 829-837. (doi: 10.2147/COPD.S125240) (PMID:28331304) (PMCID:PMC5352160)

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Abstract

Differentiating between chronic obstructive pulmonary disease (COPD) patients with normal (PiMM) or deficient (PiZZ) genetic variants of alpha-1 antitrypsin (A1AT) is important not only for understanding the pathobiology of disease progression but also for improving personalized therapies. This pilot study aimed to investigate whether urinary peptides reflect the A1AT-related phenotypes of COPD. Urine samples from 19 clinically stable COPD cases (7 PiMM and 12 PiZZ A1AT) were analyzed by capillary electrophoresis coupled to mass spectrometry. We identified 66 peptides (corresponding to 36 unique proteins) that differed between PiZZ and PiMM COPD. Among these, peptides from the collagen family were the most abundant and divergent. A logistic regression model based on COL1A1 or COL5A3 peptides enabled differentiation between PiMM and PiZZ groups, with a sensitivity of 100% and specificity of 85.71% for COL1A1 and a sensitivity of 91.67% and specificity of 85.71% for COL5A3. Furthermore, patients with PiZZ presented low levels of urinary peptides involved in lipoproteins/lipids and retinoic acid metabolism, such as apolipoprotein A-I and C4, retinol-binding protein 4 and prostaglandin-H2 d-isomerase. However, peptides of MDS1 and EVII complex locus, gelsolin and hemoglobin alpha were found in the urine of COPD cases with PiZZ, but not with PiMM. These capillary electrophoresis coupled to mass spectrometry-based results provide the first evidence that urinary peptide content differs between PiMM and PiZZ patients with COPD.

Item Type:Articles
Additional Information:This study was supported by the National Science Center, Poland (grant 2015/17/B/NZ5/01370).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mischak, Professor Harald
Authors: Carleo, A., Chorostowska-Wynimko, J., Koeck, T., Mischak, H., Czajkowska-Malinowska, M., Rozy, A., Welte, T., and Janciauskiene, S.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:International Journal of Chronic Obstructive Pulmonary Disease
Publisher:Dove Medical Press
ISSN:1176-9106
ISSN (Online):1178-2005
Copyright Holders:Copyright © 2017 Carleo et al.
First Published:First published in International Journal of COPD 12:829-837
Publisher Policy:Reproduced under a creative commons license

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