Does urinary peptide content differ between COPD patients with and without inherited alpha-1 antitrypsin deficiency?
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.
Department of Respiratory Medicine, Hannover Medical School; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), DZL Hannover, Germany.
Alfonso
A
Carleo
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
Joanna
J
Chorostowska-Wynimko
Mosaiques Diagnostics and Therapeutics AG, Hannover, Germany.
Thomas
T
Koeck
Mosaiques Diagnostics and Therapeutics AG, Hannover, Germany; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Harald
H
Mischak
Department of Lung Diseases and Respiratory Failure, Regional Center of Pulmonology, Bydgoszcz, Poland.
Małgorzata
M
Czajkowska-Malinowska
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
Adriana
A
Rozy
Department of Respiratory Medicine, Hannover Medical School; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), DZL Hannover, Germany.
Tobias
T
Welte
Department of Respiratory Medicine, Hannover Medical School; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), DZL Hannover, Germany.
Sabina
S
Janciauskiene
D000368:Aged; D015415:Biomarkers / Q000652:urine; D003937:Diagnosis, Differential; D019075:Electrophoresis, Capillary; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009154:Mutation; D010455:Peptides / Q000652:urine*; D010641:Phenotype; D010865:Pilot Projects; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D016482:Urinalysis / Q000379:methods; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000201:enzymology / Q000235:genetics / Q000652:urine*
D015415:Biomarkers; D010455:Peptides; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin
COPD; alpha-1 antitrypsin; alpha-1 antitrypsin deficiency; biomarkers; capillary electrophoresis coupled to mass spectrometry; collagen; peptides; peptidomics; phenotypes; urine