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Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease

Alpha-1 antitrypsin (AAT) is an inhibitor of neutrophil elastase and a member of the serine proteinase inhibitor (serpin) superfamily, and little is known about its activity in sickle cell disease (SCD). We hypothesize that AAT may undergo changes in SCD because of the high oxidative stress and infl...

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Autores principales: Carvalho, Magda Oliveira Seixas, Souza, André Luís Carvalho Santos, Carvalho, Mauricio Batista, Pacheco, Ana Paula Almeida Souza, Rocha, Larissa Carneiro, do Nascimento, Valma Maria Lopes, Figueiredo, Camylla Vilas Boas, Guarda, Caroline Conceição, Santiago, Rayra Pereira, Adekile, Adekunle, Goncalves, Marilda de Souza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681845/
https://www.ncbi.nlm.nih.gov/pubmed/29163550
http://dx.doi.org/10.3389/fimmu.2017.01491
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author Carvalho, Magda Oliveira Seixas
Souza, André Luís Carvalho Santos
Carvalho, Mauricio Batista
Pacheco, Ana Paula Almeida Souza
Rocha, Larissa Carneiro
do Nascimento, Valma Maria Lopes
Figueiredo, Camylla Vilas Boas
Guarda, Caroline Conceição
Santiago, Rayra Pereira
Adekile, Adekunle
Goncalves, Marilda de Souza
author_facet Carvalho, Magda Oliveira Seixas
Souza, André Luís Carvalho Santos
Carvalho, Mauricio Batista
Pacheco, Ana Paula Almeida Souza
Rocha, Larissa Carneiro
do Nascimento, Valma Maria Lopes
Figueiredo, Camylla Vilas Boas
Guarda, Caroline Conceição
Santiago, Rayra Pereira
Adekile, Adekunle
Goncalves, Marilda de Souza
author_sort Carvalho, Magda Oliveira Seixas
collection PubMed
description Alpha-1 antitrypsin (AAT) is an inhibitor of neutrophil elastase and a member of the serine proteinase inhibitor (serpin) superfamily, and little is known about its activity in sickle cell disease (SCD). We hypothesize that AAT may undergo changes in SCD because of the high oxidative stress and inflammation associated with the disease. We have found high AAT levels in SCD patients compared to controls, while mutant genotypes of SERPINA1 gene had decreased AAT levels, in both groups. AAT showed negative correlation with red blood cells, hemoglobin (Hb), hematocrit, high-density lipoprotein cholesterol, urea, creatinine, and albumin and was positively correlated with mean corpuscular Hb concentration, white blood cells, neutrophils, Hb S, bilirubin, lactate dehydrogenase, ferritin, and C-reactive protein. Patients with higher levels of AAT had more infection episodes (OR = 1.71, CI: 1.05–2.65, p = 0.02), gallstones (OR = 1.75, CI: 1.03–2.97, p = 0.02), and had more blood transfusions (OR = 2.35, CI: 1.51–3.65, p = 0.0001). Our data on AAT association with laboratory indices of hemolysis and inflammation suggest that it may be positively associated with SCD severity; the negative correlations with renal parameters suggest a cytoprotective mechanism in SCD patients. In summary, AAT may need to be included in studies related to SCD and in the discussion of further therapeutic strategies.
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spelling pubmed-56818452017-11-21 Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease Carvalho, Magda Oliveira Seixas Souza, André Luís Carvalho Santos Carvalho, Mauricio Batista Pacheco, Ana Paula Almeida Souza Rocha, Larissa Carneiro do Nascimento, Valma Maria Lopes Figueiredo, Camylla Vilas Boas Guarda, Caroline Conceição Santiago, Rayra Pereira Adekile, Adekunle Goncalves, Marilda de Souza Front Immunol Immunology Alpha-1 antitrypsin (AAT) is an inhibitor of neutrophil elastase and a member of the serine proteinase inhibitor (serpin) superfamily, and little is known about its activity in sickle cell disease (SCD). We hypothesize that AAT may undergo changes in SCD because of the high oxidative stress and inflammation associated with the disease. We have found high AAT levels in SCD patients compared to controls, while mutant genotypes of SERPINA1 gene had decreased AAT levels, in both groups. AAT showed negative correlation with red blood cells, hemoglobin (Hb), hematocrit, high-density lipoprotein cholesterol, urea, creatinine, and albumin and was positively correlated with mean corpuscular Hb concentration, white blood cells, neutrophils, Hb S, bilirubin, lactate dehydrogenase, ferritin, and C-reactive protein. Patients with higher levels of AAT had more infection episodes (OR = 1.71, CI: 1.05–2.65, p = 0.02), gallstones (OR = 1.75, CI: 1.03–2.97, p = 0.02), and had more blood transfusions (OR = 2.35, CI: 1.51–3.65, p = 0.0001). Our data on AAT association with laboratory indices of hemolysis and inflammation suggest that it may be positively associated with SCD severity; the negative correlations with renal parameters suggest a cytoprotective mechanism in SCD patients. In summary, AAT may need to be included in studies related to SCD and in the discussion of further therapeutic strategies. Frontiers Media S.A. 2017-11-06 /pmc/articles/PMC5681845/ /pubmed/29163550 http://dx.doi.org/10.3389/fimmu.2017.01491 Text en Copyright © 2017 Carvalho, Souza, Carvalho, Pacheco, Rocha, Nascimento, Figueiredo, Guarda, Santiago, Adekile and Goncalves. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Carvalho, Magda Oliveira Seixas
Souza, André Luís Carvalho Santos
Carvalho, Mauricio Batista
Pacheco, Ana Paula Almeida Souza
Rocha, Larissa Carneiro
do Nascimento, Valma Maria Lopes
Figueiredo, Camylla Vilas Boas
Guarda, Caroline Conceição
Santiago, Rayra Pereira
Adekile, Adekunle
Goncalves, Marilda de Souza
Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease
title Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease
title_full Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease
title_fullStr Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease
title_full_unstemmed Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease
title_short Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease
title_sort evaluation of alpha-1 antitrypsin levels and serpina1 gene polymorphisms in sickle cell disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681845/
https://www.ncbi.nlm.nih.gov/pubmed/29163550
http://dx.doi.org/10.3389/fimmu.2017.01491
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