Clinical trial NCT07000747: Molecular and Cellular Basis of Severe Forms of Dengue in Sickle Cell Patients
Official title: Molecular and Cellular Basis of Severe Forms of Dengue in Sickle Cell Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Dengue (Virus); Fever, Sandfly
Sickle Cell Disease
Keywords: extracellular vesicles
blood immune cells
Dengue virus
Lead sponsor: Centre Hospitalier Universitaire de la Guadeloupe
Sponsor class: OTHER
First posted: 2025-06-03
Enrollment: 130
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients from 6 to 25 years, with sicke cell disease in a steady state at inclusion

Brief summary: Dengue virus (DENV) belongs to the genus of Flavivirus transmitted by the mosquito Aedes aegypti and is responsible for an infectious disease associated with different forms and severities such as dengue hemorrhagic fever or shock syndrome. Several recent reports have shown that sickle cell patients exhibited an increased risk of developing severe forms of dengue episodes compared to non-sickle cell subjects. Furthermore, among major sickle cell syndromes, these studies suggest that SC patients are at the highest risk of death during these infectious episodes although this sickle cell syndrome is generally associated with a more moderate expression of sickle cell disease. However, the mechanisms involved remain unknown to date.

The aim of the present study is to identify the molecular and cellular basis of this increased severity of dengue in SC patients. We hypothesize an exacerbation during DENV infection of the inflammatory response in SC patients compared to SS patients.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Lymphocyte subpopulations measured by flow cytometry at steady-state
timeFrame: baseline
Secondary outcomes:
measure: activation status of immune cells induced by DENV
timeFrame: baseline
measure: Comparative Analysis of NET Formation Induced by Sickle Cell-Derived Microparticles With or Without Mosquito Saliva
timeFrame: baseline
measure: Impact of SS and SC Blood Profiles on Aedes aegypti Biting Behavior and Dengue Virus Transmission
timeFrame: baseline
Other outcomes:
Locations:
city: Pointe-à-Pitre
country: Guadeloupe
facility: Chu de La Guadeloupe
Study officials:
affiliation: CHU de la Guadeloupe
name: Maryse Etienne-Julan, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: