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Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients

Sickle Cell Anemia (SCA) is the most common genetic disorder around the world. The mutation in the β-globin gene is responsible for a higher hemolysis rate, with further involvement of immunological molecules, especially cytokines, chemokines, growth factors, and anaphylatoxins. These molecules are...

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Autores principales: Silva-Junior, Alexander Leonardo, Garcia, Nadja Pinto, Cardoso, Evilázio Cunha, Dias, Stephanny, Tarragô, Andrea Monteiro, Fraiji, Nelson Abrahim, Gomes, Matheus Souza, Amaral, Laurence Rodrigues, Teixeira-Carvalho, Andréa, Martins-Filho, Olindo Assis, De Paula, Erich Vinicius, Costa, Allyson Guimarães, Malheiro, Adriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990896/
https://www.ncbi.nlm.nih.gov/pubmed/33776989
http://dx.doi.org/10.3389/fimmu.2021.559925
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author Silva-Junior, Alexander Leonardo
Garcia, Nadja Pinto
Cardoso, Evilázio Cunha
Dias, Stephanny
Tarragô, Andrea Monteiro
Fraiji, Nelson Abrahim
Gomes, Matheus Souza
Amaral, Laurence Rodrigues
Teixeira-Carvalho, Andréa
Martins-Filho, Olindo Assis
De Paula, Erich Vinicius
Costa, Allyson Guimarães
Malheiro, Adriana
author_facet Silva-Junior, Alexander Leonardo
Garcia, Nadja Pinto
Cardoso, Evilázio Cunha
Dias, Stephanny
Tarragô, Andrea Monteiro
Fraiji, Nelson Abrahim
Gomes, Matheus Souza
Amaral, Laurence Rodrigues
Teixeira-Carvalho, Andréa
Martins-Filho, Olindo Assis
De Paula, Erich Vinicius
Costa, Allyson Guimarães
Malheiro, Adriana
author_sort Silva-Junior, Alexander Leonardo
collection PubMed
description Sickle Cell Anemia (SCA) is the most common genetic disorder around the world. The mutation in the β-globin gene is responsible for a higher hemolysis rate, with further involvement of immunological molecules, especially cytokines, chemokines, growth factors, and anaphylatoxins. These molecules are responsible for inducing and attracting immune cells into circulation, thus contributing to increases in leukocytes and other pro-inflammatory mediators, and can culminate in a vaso-occlusive crisis (VOC). This study aimed to characterize the levels of these molecules in SCA patients in different clinical conditions in order to identify potential hallmarks of inflammation in these patients. An analytical prospective study was conducted using the serum of SCA patients in steady-state (StSt; n = 27) and VOC (n = 22), along with 53 healthy donors (HD). Samples from the VOC group were obtained on admission and on discharge, in the convalescent phase (CV). Levels of chemokines (CXCL8, CXCL10, CL2, CLL3, CCL4, CL5, and CCL11), cytokines (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17A, TNF-α, and IFN-γ) and growth factors (VEGF, FGFb, PDGF-BB, GM-CSF, and G-CSF) were measured using a Luminex assay, and anaphylatoxins (C3a, C4a, and C5a) were measured using Cytometric Bead Array. SCA patients in StSt showed a pro-inflammatory profile, and were indicated as being higher producers of CCL2, IL-1β, IL-12p70, IFN-γ, IL-17A, and GM-CSF, while VOC is highlighted by molecules IL-4 and IL-5, but also IL-2, IL-7, PDGF-BB, and G-CSF. PDGF-BB and IL-1ra seemed to be two important hallmarks for the acute-to-chronic stage, due to their significant decrease after crisis inflammation and statistical difference in VOC and CV groups. These molecules show higher levels and a strong correlation with other molecules in VOC. Furthermore, they remain at higher levels even after crisis recovery, which suggest their importance in the role of inflammation during crisis and participation in immune cell adhesion and activation. These results support a relevant role of cytokines, neutrophil and monocytes, since these may act as markers of VOC inflammation in SCA patients.
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spelling pubmed-79908962021-03-26 Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients Silva-Junior, Alexander Leonardo Garcia, Nadja Pinto Cardoso, Evilázio Cunha Dias, Stephanny Tarragô, Andrea Monteiro Fraiji, Nelson Abrahim Gomes, Matheus Souza Amaral, Laurence Rodrigues Teixeira-Carvalho, Andréa Martins-Filho, Olindo Assis De Paula, Erich Vinicius Costa, Allyson Guimarães Malheiro, Adriana Front Immunol Immunology Sickle Cell Anemia (SCA) is the most common genetic disorder around the world. The mutation in the β-globin gene is responsible for a higher hemolysis rate, with further involvement of immunological molecules, especially cytokines, chemokines, growth factors, and anaphylatoxins. These molecules are responsible for inducing and attracting immune cells into circulation, thus contributing to increases in leukocytes and other pro-inflammatory mediators, and can culminate in a vaso-occlusive crisis (VOC). This study aimed to characterize the levels of these molecules in SCA patients in different clinical conditions in order to identify potential hallmarks of inflammation in these patients. An analytical prospective study was conducted using the serum of SCA patients in steady-state (StSt; n = 27) and VOC (n = 22), along with 53 healthy donors (HD). Samples from the VOC group were obtained on admission and on discharge, in the convalescent phase (CV). Levels of chemokines (CXCL8, CXCL10, CL2, CLL3, CCL4, CL5, and CCL11), cytokines (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17A, TNF-α, and IFN-γ) and growth factors (VEGF, FGFb, PDGF-BB, GM-CSF, and G-CSF) were measured using a Luminex assay, and anaphylatoxins (C3a, C4a, and C5a) were measured using Cytometric Bead Array. SCA patients in StSt showed a pro-inflammatory profile, and were indicated as being higher producers of CCL2, IL-1β, IL-12p70, IFN-γ, IL-17A, and GM-CSF, while VOC is highlighted by molecules IL-4 and IL-5, but also IL-2, IL-7, PDGF-BB, and G-CSF. PDGF-BB and IL-1ra seemed to be two important hallmarks for the acute-to-chronic stage, due to their significant decrease after crisis inflammation and statistical difference in VOC and CV groups. These molecules show higher levels and a strong correlation with other molecules in VOC. Furthermore, they remain at higher levels even after crisis recovery, which suggest their importance in the role of inflammation during crisis and participation in immune cell adhesion and activation. These results support a relevant role of cytokines, neutrophil and monocytes, since these may act as markers of VOC inflammation in SCA patients. Frontiers Media S.A. 2021-03-11 /pmc/articles/PMC7990896/ /pubmed/33776989 http://dx.doi.org/10.3389/fimmu.2021.559925 Text en Copyright © 2021 Silva-Junior, Garcia, Cardoso, Dias, Tarragô, Fraiji, Gomes, Amaral, Teixeira-Carvalho, Martins-Filho, De Paula, Costa and Malheiro. 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) and the copyright owner(s) 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
Silva-Junior, Alexander Leonardo
Garcia, Nadja Pinto
Cardoso, Evilázio Cunha
Dias, Stephanny
Tarragô, Andrea Monteiro
Fraiji, Nelson Abrahim
Gomes, Matheus Souza
Amaral, Laurence Rodrigues
Teixeira-Carvalho, Andréa
Martins-Filho, Olindo Assis
De Paula, Erich Vinicius
Costa, Allyson Guimarães
Malheiro, Adriana
Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients
title Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients
title_full Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients
title_fullStr Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients
title_full_unstemmed Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients
title_short Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients
title_sort immunological hallmarks of inflammatory status in vaso-occlusive crisis of sickle cell anemia patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990896/
https://www.ncbi.nlm.nih.gov/pubmed/33776989
http://dx.doi.org/10.3389/fimmu.2021.559925
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