Molecular and Cellular Basis of Severe Forms of Dengue in Sickle Cell Patients

More precisely, the objective is to determine and compare the different cellular and molecular inflammatory mediators between SS and SC patients at baseline, and to study DENV-induced activation of various blood figurative elements isolated from uninfected sickle cell patients in vitro.

Given the essential role of immune cells in the DENV cycle and in the innate and adaptive immune responses of the host, understanding the changes induced by viral infection in Peripheral Blood Mononuclear Cells (PBMC) and Monocyte-Derived Dendritic Cells (MDDC) remains a priority. The effect of DENV or DENV-Associated Molecular Patterns (PAMPs) will therefore be studied in vitro on purified cells from SC and SS patients.

The impact of MicroParticles (MPs), known to be involved in the pathogenesis of severe dengue forms and in sickle cell disease, will also be evaluated on two cell types: endothelial cells and neutrophils, the latter exhibiting exacerbated activation and production of Neutrophil Extracellular Traps (NETs).

Considering the influence of mosquito saliva components on the pathogenesis of arboviruses (including DENV) in vertebrate hosts through the amplification of inflammatory responses, a comparative analysis of cellular and molecular inflammatory mediators released following exposure of blood cells from SS and SC patients to DENV and Aedes aegypti saliva will be conducted in vitro.

Lastly, the differential blood profiles of SS and SC patients will be assessed for their impact on the vector competence of Aedes aegypti mosquitoes in transmitting DENV.

Inclusion criteria

• patients with SS or SC SCD or controls with hemoglobin AA
• diagnosis of SCD performed by electrophoresis or HPLC in a reference laboratory for hemoglobinopathies
• patients older than 6 years and younger than 25 at inclusion
• clinically in a steady state at inclusion (without complication during the last month and without transfusion in the three last months)
• patients followed up for SCD at the sickle cell center of Guadeloupe (University hospital of Guadeloupe, Pointe-à-Pitre)
• patients or legal representatives of minors who will provide written informed consent in accordance with the Declaration of Helsinki
• patients affiliated to national social security
• the control group (AA subjects) will be recruited among volunteers recruited by posters

Exclusion criteria

• patients with SS or SC SCD or controls with hemoglobin AA
• diagnosis of SCD performed by electrophoresis or HPLC in a reference laboratory for hemoglobinopathies
• patients older than 6 years and younger than 25 at inclusion
• clinically in a steady state at inclusion (without complication during the last month and without transfusion in the three last months)
• patients followed up for SCD at the sickle cell center of Guadeloupe (University hospital of Guadeloupe, Pointe-à-Pitre)
• patients or legal representatives of minors who will provide written informed consent in accordance with the Declaration of Helsinki
• patients affiliated to national social security
• the control group (AA subjects) will be recruited among volunteers recruited by posters