Éditeur(s) : HAL CCSD
Résumé : L'HNE et la Lf sont des protéines particulières car impliquées dans de nombreux processus physiologiques et pathologiques différents, connues comme des marqueurs de l'inflammation (inflammations pulmonaires et maladie de Crohn). Nous avons déterminé leur mécanisme d'action dans le cadre de la drépanocytose, une maladie génétique particulièrement polymorphe. Nous avons montré la présence de mutations inédites des gènes codant ces deux protéines dans le cas de la drépanocytose, mutations pouvant affecter le niveau d'expression et la structure de ces protéines. Des études sont en cours actuellement pour déterminer l'effet de ces mutations.
https://hal.archives-ouvertes.fr/hal-00201470

hal-00201470
https://hal.archives-ouvertes.fr/hal-00201470
https://hal.archives-ouvertes.fr/hal-00201470/document
https://hal.archives-ouvertes.fr/hal-00201470/file/PolyHL_Marianne_v1.pdf

Éditeur(s) : HAL CCSD
Résumé : ABSTRACT Infectious complications are a leading cause of morbidity and mortality in patients with sickle cell disease. The exact reasons of the propensity of sickle cell patients to infection are not clear and are matter of debate. Besides, there is a striking variability of the clinical course of the disease between patients. This drew many scientists' attention. Genetic factors have been investigated as potential factor risks for infection in sickle cell patients, for example: HLA system; genes encoding Fc Human Immunoglobulin G receptor IIA, mannose-binding protein, and myeloperoxidase. Associations have been found, but all scientists agree that investigations have to be furthered. We investigated an association between HLA DRB1 and DQB1 polymorphism and infectious complications in sickle cell patients. Genotype frequencies were different between cases and controls for DRB1 locus. Indeed, HLA-DRB1*11 frequency was significantly higher in patients without infections than in patients with infections (χ² = 5.02; p = 0.025).
https://hal.archives-ouvertes.fr/hal-00387082

hal-00387082
https://hal.archives-ouvertes.fr/hal-00387082
https://hal.archives-ouvertes.fr/hal-00387082/document
https://hal.archives-ouvertes.fr/hal-00387082/file/MO_JOANNES_et_al_HLA_and_SCD.pdf

Éditeur(s) : HAL CCSD
Résumé : Red blood cell hemodynamics influence blood rheology and thus circulatory function. Different authors showed that red blood cells are heterogeneous in blood flow. This heterogeneity could be explained by physical characteristics such as morphology, aggregability and deformability, but also by cellular and molecular environment. All these notions are found in sickle cell disease where sickle red blood cells become more rigid, leading to vascular occlusions, increased with an inflammatory context. In a preceding study, our results showed that velocity heterogeneity allow RBC classification, leading to different RBC sub-groups, using a dynamical approach and flow studies. In order to have a better understanding of the physiological meaning of such an heterogeneity, dynamical velocity experiences have been conducted in the case of normal and sickle red blood cells with different endothelial activations by proinflammatory cytokines, under a constant venular flow. Thus, normal and sickle red blood cells are classified into different sub-groups, showing their heterogeneity. Moreover, sub-population velocities and distribution evolve differently according to vascular state or treatment. These results show that red blood cell velocities and rheology depend on vascular environment and red blood cell morphology. However, the physiological meaning of this behavior should be explained by cellular and molecular effects of such activation.
https://hal.archives-ouvertes.fr/hal-00201461

hal-00201461
https://hal.archives-ouvertes.fr/hal-00201461
https://hal.archives-ouvertes.fr/hal-00201461/document
https://hal.archives-ouvertes.fr/hal-00201461/file/RBCV_Marianne_v1.pdf

Éditeur(s) : HAL CCSD
Résumé : Background Acute splenic sequestration is one of the major clinical forms of sickle cell disease. This potentially life-threatening complication is defined by a rapid sequestration of sickle red blood cells in the spleen. Approximately 30% of young patients will develop this complication and 49% of them will have recurrences. Methods The decision tree method is a statistical method that can act as a medical decision tool in the case of a complex biological problem. The decision tree method is used here to determine the variables involved in the severity and recurrence of acute splenic sequestration crises. Results A prior decision tree shows that platelet level, variation in spleen size, patient age and hygrometry also called relative humidity define acute splenic sequestration severity. A second one shows that spleen size variation, atmospheric pressure and patient age define recurrence. Conclusions For the first time, biological and environmental parameters are combined to discover some interesting rules which can lead to more accurate evaluations of acute splenic sequestration severity and recurrence. Thus, this method provides a sharp diagnostic tool which could improve medical treatment for better patient care.
https://hal.archives-ouvertes.fr/hal-00201460

hal-00201460
https://hal.archives-ouvertes.fr/hal-00201460
https://hal.archives-ouvertes.fr/hal-00201460v2/document
https://hal.archives-ouvertes.fr/hal-00201460/file/DT_Marianne_v2.pdf

Éditeur(s) : HAL CCSD
Résumé : ABSTRACT Infectious complications are a leading cause of morbidity and mortality in patients with sickle cell disease. Several mechanisms are supposed to contribute to this susceptibility. The exact reasons of the propensity of sickle cell patients to infection are not clear and are still matter of debate. Interferon gamma is a key cytokine involved namely in the defence against intracellular pathogens. We investigated a possible association of +874 T/A IFNγ polymorphism and infectious complications in sickle cell patients. Seventy-two sickle cell patients were typed for +874 T/A IFNγ polymorphism. Genotype frequencies were different between cases and controls. Indeed, T allele frequency was significantly higher in patients with infections than in patients without infections (χ² = 6.23 ; p = 0.013). Our results suggest that +874 T/A IFNγ polymorphism is associated with infectious complications in sickle cell patients. The T allele could be involved in infections in sickle cell patients.
https://hal.archives-ouvertes.fr/hal-00387081

hal-00387081
https://hal.archives-ouvertes.fr/hal-00387081
https://hal.archives-ouvertes.fr/hal-00387081/document
https://hal.archives-ouvertes.fr/hal-00387081/file/MO_Joannes_et_al._IFNG_polymorphism_and_sickle_cell_disease.pdf