Caracterização do perfil de moléculas do sistema complemento em pacientes pediátricos com leucemia linfoblástica aguda de células B

Abstract

The complement system (SC) plays an essential role in innate and adaptive immune responses. Studies indicate that in the tumor microenvironment, SC activation may be involved in both the activation of antitumor cytotoxic immune responses and tumor development, in addition to demonstrating interactions with chemokines and cytokines. To better contribute to the knowledge about the role of SC, this study aimed to characterize the profile of SC molecules in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) undergoing remission chemotherapy. An analytical observational study, of the longitudinal and prospective type, was carried out at the Hospital Foundation of Hematology and Hemotherapy of Amazonas (HEMOAM) in partnership with the Integrated Research Group on Biomarkers of the René Rachou Institute (IRR/FIOCRUZ-Minas). For this study, bone marrow (BM) and peripheral blood (PB) samples from newly diagnosed patients with B-ALL were used, collected at 4 time points of remission chemotherapy, referred to as: day of diagnosis (D0), day 15 of remission induction therapy (D15), end of remission induction therapy (D35) and day 84 (D84) of remission consolidation therapy, together with the patients' demographic and clinical-laboratory data. SP samples obtained from children without leukemia and without alterations in the blood count, who comprised the control group (CG), were also used. The samples were sent to IRR/FIOCRUZ Minas for quantification of SC molecules (C1q, C3, C3b/iC3b, C4,Factor B and Factor H), chemokines (CCL2 and CXCL8), pro-inflammatory cytokines (IL-1β,IL-6, TNF-α and INF-γ) and regulatory cytokines (IL-1Ra and IL-10), through the Luminex technique, using the Luminex 200 system and Bioplex Manager software. Our results allowed the identification of C1q, C3, C3b, Factor B and Factor H as positive predictive biomarkers in patients with B-ALL who completed therapy, while the cytokines IL-10, IL-1Ra, CXCL8 and IL-1β were presented as biomarkers in patients who died. Finally, we conclude that the dual role of SC molecules suggests an immunological profile capable of contributing to risk stratification and the development of new therapeutic strategies for pediatric patients with B-ALL through the identification of immunological biomarkers.