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The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients

Alpha-1-Antitrypsin (AAT) is a protein of the SERPINA1 gene. A single amino acid mutation (Lys342Glu) results in an expression of misfolded Z-AAT protein, which has a high propensity to intra- and extra-cellular polymerization. Here, we asked whether levels of circulating Z-AAT polymers are associat...

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Autores principales: Sark, Annelot D., Fromme, Malin, Olejnicka, Beata, Welte, Tobias, Strnad, Pavel, Janciauskiene, Sabina, Stolk, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945708/
https://www.ncbi.nlm.nih.gov/pubmed/35327571
http://dx.doi.org/10.3390/biom12030380
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author Sark, Annelot D.
Fromme, Malin
Olejnicka, Beata
Welte, Tobias
Strnad, Pavel
Janciauskiene, Sabina
Stolk, Jan
author_facet Sark, Annelot D.
Fromme, Malin
Olejnicka, Beata
Welte, Tobias
Strnad, Pavel
Janciauskiene, Sabina
Stolk, Jan
author_sort Sark, Annelot D.
collection PubMed
description Alpha-1-Antitrypsin (AAT) is a protein of the SERPINA1 gene. A single amino acid mutation (Lys342Glu) results in an expression of misfolded Z-AAT protein, which has a high propensity to intra- and extra-cellular polymerization. Here, we asked whether levels of circulating Z-AAT polymers are associated with the severity of lung disease, liver disease, or both. We obtained cross sectional data from the Dutch part of the Alpha1 International Registry of 52 ZZ-AAT patients who performed a pulmonary function test and donated a blood sample on the same day. From the Alpha-1 Liver Aachen Registry, we obtained a cohort of 40 ZZ-AAT patients with available data on their liver function. The levels of plasma Z-AAT polymers were determined using a LG96 monoclonal antibody-based sandwich ELISA. In a Dutch cohort, the median plasma level of Z-AAT polymers of patients diagnosed for pulmonary disease was 947.5 µg/mL (733.6–1218 µg/mL (95% CI)), which did not correlate with airflow obstruction or gas transfer value. In the Alpha-1 liver patient cohort, the median polymer level was 1245.9 µg/mL (753–2034 µg/mL (95% CI)), which correlated with plasma gamma-glutamyl transferase (GGT, rs = 0.57, p = 0.001), glutamate dehydrogenase (GLDH, rs = 0.48, p = 0.002) and triglycerides (TG, rs = 0.48, p = 0.0046). A Wilcoxon rank test showed higher Z-AAT polymer values for the liver over the lung group (p < 0.0001). These correlations support a possible link between plasma Z-AAT polymers and the liver function.
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spelling pubmed-89457082022-03-25 The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients Sark, Annelot D. Fromme, Malin Olejnicka, Beata Welte, Tobias Strnad, Pavel Janciauskiene, Sabina Stolk, Jan Biomolecules Article Alpha-1-Antitrypsin (AAT) is a protein of the SERPINA1 gene. A single amino acid mutation (Lys342Glu) results in an expression of misfolded Z-AAT protein, which has a high propensity to intra- and extra-cellular polymerization. Here, we asked whether levels of circulating Z-AAT polymers are associated with the severity of lung disease, liver disease, or both. We obtained cross sectional data from the Dutch part of the Alpha1 International Registry of 52 ZZ-AAT patients who performed a pulmonary function test and donated a blood sample on the same day. From the Alpha-1 Liver Aachen Registry, we obtained a cohort of 40 ZZ-AAT patients with available data on their liver function. The levels of plasma Z-AAT polymers were determined using a LG96 monoclonal antibody-based sandwich ELISA. In a Dutch cohort, the median plasma level of Z-AAT polymers of patients diagnosed for pulmonary disease was 947.5 µg/mL (733.6–1218 µg/mL (95% CI)), which did not correlate with airflow obstruction or gas transfer value. In the Alpha-1 liver patient cohort, the median polymer level was 1245.9 µg/mL (753–2034 µg/mL (95% CI)), which correlated with plasma gamma-glutamyl transferase (GGT, rs = 0.57, p = 0.001), glutamate dehydrogenase (GLDH, rs = 0.48, p = 0.002) and triglycerides (TG, rs = 0.48, p = 0.0046). A Wilcoxon rank test showed higher Z-AAT polymer values for the liver over the lung group (p < 0.0001). These correlations support a possible link between plasma Z-AAT polymers and the liver function. MDPI 2022-02-28 /pmc/articles/PMC8945708/ /pubmed/35327571 http://dx.doi.org/10.3390/biom12030380 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sark, Annelot D.
Fromme, Malin
Olejnicka, Beata
Welte, Tobias
Strnad, Pavel
Janciauskiene, Sabina
Stolk, Jan
The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients
title The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients
title_full The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients
title_fullStr The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients
title_full_unstemmed The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients
title_short The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients
title_sort relationship between plasma alpha-1-antitrypsin polymers and lung or liver function in zz alpha-1-antitrypsin-deficient patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945708/
https://www.ncbi.nlm.nih.gov/pubmed/35327571
http://dx.doi.org/10.3390/biom12030380
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