Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis
Background. Sickle cell anemia (SCA) is associated with a chronic proinflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vasoocclusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflamma...
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| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/4585704 |
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| author | Nadja Pinto Garcia Alexander Leonardo S. Júnior Geyse Adriana S. Soares Thainá Cristina C. Costa Alicia Patrine C. dos Santos Allyson Guimarães Costa Andréa Monteiro Tarragô Rejane Nina Martins Flávia do Carmo Leão Pontes Emerson Garcia de Almeida Erich Vinícius de Paula Olindo Assis Martins-Filho Adriana Malheiro |
| author_facet | Nadja Pinto Garcia Alexander Leonardo S. Júnior Geyse Adriana S. Soares Thainá Cristina C. Costa Alicia Patrine C. dos Santos Allyson Guimarães Costa Andréa Monteiro Tarragô Rejane Nina Martins Flávia do Carmo Leão Pontes Emerson Garcia de Almeida Erich Vinícius de Paula Olindo Assis Martins-Filho Adriana Malheiro |
| author_sort | Nadja Pinto Garcia |
| collection | DOAJ |
| description | Background. Sickle cell anemia (SCA) is associated with a chronic proinflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vasoocclusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflammatory cytokines. The immune system has a close connection with morbidity in SCA, but further studies are needed to uncover the involvement of innate and adaptive immunities in modulating the SCA physiopathology. We performed measurements of the frequency of innate and adaptive immunity cells, cytokines, chemokines, and growth factors and immunophenotyping of Toll-like receptor and adhesion molecule expression in the blood of SCA patients and healthy donors to evaluate the different profiles of these biomarkers, the relationship among them, and their correlation to laboratory records and death risk. Material and Methods. Immunophenotyping of cells, Toll-like receptors, and adhesion molecules were performed from peripheral blood samples of SCA patients and healthy donors by flow cytometry and cytokine/chemokine/growth factor measurement by the Luminex technique performed from the serum of the same subjects. Results. Cells of adaptive immunity such as IL-12, IL-17, and IL-10 cytokines; IL-8, IP-10, MIP-1α, MIP-1β, and RANTES chemokines; and VEGF, FGF-basic, and GM-CSF growth factors were higher in SCA patients than healthy donors regardless of any laboratorial and clinical condition. However, high death risk appears to have relevant biomarkers. Conclusion. In the SCA pathophysiology at steady state, there is a broad immunological biomarker crosstalk highlighted by TCD4+CD69+ lymphocytes, IL-12 and IL-17 inflammatory and IL-10 regulatory cytokines, MIP-1α, MIP-1β, and IP-10 chemokines, and VEGF growth factor. High expression of TLR2 in monocytes and VLA-4 in TCD8+ lymphocytes and high levels of MIP-1β and RANTES appear to be relevant in high death risk conditions. The high reticulocytosis and high death risk conditions present common correlations, and there seems to be a balance by the Th2 profile. |
| format | Article |
| id | doaj-art-f08c59a896fb4a33b54c683308ef2ff3 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-f08c59a896fb4a33b54c683308ef2ff32025-02-03T01:26:57ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/45857044585704Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 AxisNadja Pinto Garcia0Alexander Leonardo S. Júnior1Geyse Adriana S. Soares2Thainá Cristina C. Costa3Alicia Patrine C. dos Santos4Allyson Guimarães Costa5Andréa Monteiro Tarragô6Rejane Nina Martins7Flávia do Carmo Leão Pontes8Emerson Garcia de Almeida9Erich Vinícius de Paula10Olindo Assis Martins-Filho11Adriana Malheiro12Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas (UFAM), 69077-000 Manaus, AM, BrazilPrograma de Pós-Graduação em Ciências Aplicadas a Hematologia, Universidade Estadual do Amazonas (PPCAH/UEA), 69065-001 Manaus, AM, BrazilPrograma de Apoio a Iniciação Científica, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), 69050-001 Manaus, AM, BrazilPrograma de Pós-Graduação em Ciências Aplicadas a Hematologia, Universidade Estadual do Amazonas (PPCAH/UEA), 69065-001 Manaus, AM, BrazilPrograma de Apoio a Iniciação Científica, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), 69050-001 Manaus, AM, BrazilPrograma de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas (UFAM), 69077-000 Manaus, AM, BrazilLaboratório de Genômica, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), 69050-001 Manaus, AM, BrazilLaboratório de Genômica, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), 69050-001 Manaus, AM, BrazilLaboratório de Genômica, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), 69050-001 Manaus, AM, BrazilPrograma de Pós-Graduação em Ciências Aplicadas a Hematologia, Universidade Estadual do Amazonas (PPCAH/UEA), 69065-001 Manaus, AM, BrazilPrograma de Pós-Graduação em Ciências Aplicadas a Hematologia, Universidade Estadual do Amazonas (PPCAH/UEA), 69065-001 Manaus, AM, BrazilGrupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou/Fiocruz Minas, 30190-002 Belo Horizonte, MG, BrazilPrograma de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas (UFAM), 69077-000 Manaus, AM, BrazilBackground. Sickle cell anemia (SCA) is associated with a chronic proinflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vasoocclusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflammatory cytokines. The immune system has a close connection with morbidity in SCA, but further studies are needed to uncover the involvement of innate and adaptive immunities in modulating the SCA physiopathology. We performed measurements of the frequency of innate and adaptive immunity cells, cytokines, chemokines, and growth factors and immunophenotyping of Toll-like receptor and adhesion molecule expression in the blood of SCA patients and healthy donors to evaluate the different profiles of these biomarkers, the relationship among them, and their correlation to laboratory records and death risk. Material and Methods. Immunophenotyping of cells, Toll-like receptors, and adhesion molecules were performed from peripheral blood samples of SCA patients and healthy donors by flow cytometry and cytokine/chemokine/growth factor measurement by the Luminex technique performed from the serum of the same subjects. Results. Cells of adaptive immunity such as IL-12, IL-17, and IL-10 cytokines; IL-8, IP-10, MIP-1α, MIP-1β, and RANTES chemokines; and VEGF, FGF-basic, and GM-CSF growth factors were higher in SCA patients than healthy donors regardless of any laboratorial and clinical condition. However, high death risk appears to have relevant biomarkers. Conclusion. In the SCA pathophysiology at steady state, there is a broad immunological biomarker crosstalk highlighted by TCD4+CD69+ lymphocytes, IL-12 and IL-17 inflammatory and IL-10 regulatory cytokines, MIP-1α, MIP-1β, and IP-10 chemokines, and VEGF growth factor. High expression of TLR2 in monocytes and VLA-4 in TCD8+ lymphocytes and high levels of MIP-1β and RANTES appear to be relevant in high death risk conditions. The high reticulocytosis and high death risk conditions present common correlations, and there seems to be a balance by the Th2 profile.http://dx.doi.org/10.1155/2020/4585704 |
| spellingShingle | Nadja Pinto Garcia Alexander Leonardo S. Júnior Geyse Adriana S. Soares Thainá Cristina C. Costa Alicia Patrine C. dos Santos Allyson Guimarães Costa Andréa Monteiro Tarragô Rejane Nina Martins Flávia do Carmo Leão Pontes Emerson Garcia de Almeida Erich Vinícius de Paula Olindo Assis Martins-Filho Adriana Malheiro Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis Journal of Immunology Research |
| title | Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis |
| title_full | Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis |
| title_fullStr | Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis |
| title_full_unstemmed | Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis |
| title_short | Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis |
| title_sort | sickle cell anemia patients display an intricate cellular and serum biomarker network highlighted by tcd4 cd69 lymphocytes il 17 mip 1β il 12 vegf and il 10 ip 10 axis |
| url | http://dx.doi.org/10.1155/2020/4585704 |
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