Perfil imune fenotípico associado a parâmetros laboratoriais e gravidade clínica na anemia falciforme

Abstract

Sickle cell anemia (SCA) is associated with a chronic pro-inflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vaso occlusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflammatory cytokines. The immune system has a close connection with morbidity in sickle cell anemia, but further studies are needed to uncover the involvement of innate and adaptive immunities in modulating the SCA physiopathology. We performed the frequency of innate and adaptive immunity cells, cytokines, chemokines and growth factors measurement, Toll-like receptors and adhesion molecules expression in the blood of SCA patients and healthy donors to evaluate the different profile of these biomarkers, the relationship among them and its correlation to laboratory records and death risk. The immunophenotyping of cells, Toll-like receptors, adhesion molecules and cytokine/chemokine/growth factors measurement were performed from peripheral blood samples from SCA patients and healthy donors by flow cytometry and luminex techniques, respectively. The cells of the adaptive immunity, Th1, Th17 and regulatory cytokines, IL-8, IP-10, MIP-α, MIP- and RANTES chemokines and VEGF, bFGF and GM-CSF growth factors were higher in SCA patients than healthy donors regardless any laboratorial and clinical condition. Although, high death risk appears to have relevant biomarkers. In the SCA pathophysiology at steady state there are a broad immunological biomarker cross-talk highlighted by TCD4+CD69+ lymphocytes, IL-12 and IL-17 inflammatory and IL-10 regulatory cytokines, MIP-α, MIP- and IP-10 chemokines and growth factor VEGF. High expression of TLR2 in monocytes and VLA-4 in TCD8+ lymphocytes and high levels of MIP- and RANTES appears to be relevant in high death risk condition. The high reticulocytosis and high death risk conditions present commons correlations there seems to be balance by Th2 profile. However, further studies are needed to establish a selective biomarker and to better understand this complex pathophysiological mechanism of sickle cell anemia.