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

Author:

Garcia Nadja Pinto12ORCID,Júnior Alexander Leonardo S.3ORCID,Soares Geyse Adriana S.4,Costa Thainá Cristina C.3,dos Santos Alicia Patrine C.4,Costa Allyson Guimarães123ORCID,Tarragô Andréa Monteiro2ORCID,Martins Rejane Nina2,do Carmo Leão Pontes Flávia2,de Almeida Emerson Garcia3,de Paula Erich Vinícius35,Martins-Filho Olindo Assis6,Malheiro Adriana123ORCID

Affiliation:

1. Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas (UFAM), 69077-000 Manaus, AM, Brazil

2. Laboratório de Genômica, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), 69050-001 Manaus, AM, Brazil

3. Programa de Pós-Graduação em Ciências Aplicadas a Hematologia, Universidade Estadual do Amazonas (PPCAH/UEA), 69065-001 Manaus, AM, Brazil

4. Programa de Apoio a Iniciação Científica, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), 69050-001 Manaus, AM, Brazil

5. Departamento de Clínica Médica da Faculdade de Ciências Médicas da UNICAMP, 13083-970 Campinas, SP, Brazil

6. Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou/Fiocruz Minas, 30190-002 Belo Horizonte, MG, Brazil

Abstract

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.

Funder

Fiocruz Minas

Publisher

Hindawi Limited

Subject

Immunology,General Medicine,Immunology and Allergy

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