A primary immunodeficiency characterized by defective immunoglobulin class switch recombination and impaired DNA repair

Immunoglobulin class switch recombination (CSR) deficiencies are rare primary immunodeficiencies, characterized by a lack of switched isotype (IgG, IgA, or IgE) production, variably associated with abnormal somatic hypermutation (SHM). Deficiencies in CD40 ligand, CD40, activation-induced cytidine deaminase, and uracil-N-glycosylase may account for this syndrome. We previously described another Ig CSR deficiency condition, characterized by a defect in CSR downstream of the generation of double-stranded DNA breaks in switch (S) μ regions. Further analysis performed with the cells of five affected patients showed that the Ig CSR deficiency was associated with an abnormal formation of the S junctions characterized by microhomology and with increased cell radiosensitivity. In addition, SHM was skewed toward transitions at G/C residues. Overall, these findings suggest that a unique Ig CSR deficiency phenotype could be related to an as-yet-uncharacterized defect in a DNA repair pathway involved in both CSR and SHM events

Infections graves chez l enfant drépanocytaire (apport du dosage des antibiotiques dans la prise en charge)

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Thérapeutiques transfusionnelles dans la prise en charge de la vasculopathie cérébrale de l enfant drépanocytaire : échanges transfusionnels versus saignées-transfusions, bénéfice/risque des deux méthodes

La drépanocytose est une maladie génétique de l hémoglobine, exposant notamment les patients à un risque d accident vasculaire cérébral, qui peut être prévenu par la réalisation de transfusions sanguines ou d échanges transfusionnels itératifs. Nous avons décrit et comparé, en termes d efficacité et de tolérance, les protocoles transfusionnels proposés aux enfants drépanocytaires ayant une vasculopathie cérébrale dans 2 centres hospitaliers : dans l un, un programme d échanges transfusionnels manuels ou automatisés, et dans l autre un programme de transfusions itératives et de saignées-transfusions. L échange transfusionnel automatisé est la méthode qui permet la meilleure diminution du taux d HbS par séance en comparaison avec l échange transfusionnel manuel et la transfusion simple. En ce qui concerne la normalisation de la vasculopathie cérébrale, il n existait pas de supériorité des échanges transfusionnel, manuels et automatisés, par rapport aux transfusions simples. Le taux d allo-immunisation était plus important dans le groupe de transfusions itératives que dans le groupe d échanges transfusionnels. Les patients sous transfusions itératives présentaient une surcharge martiale plus fréquente et plus importante que les patients sous échanges transfusionnels. En conclusion, la réalisation de transfusions itératives chez les enfants drépanocytaires permet d améliorer la vasculopathie cérébrale de manière aussi efficace que les échanges transfusionnels manuels et automatisés. En revanche, cette méthode comporte d avantages de risques en termes d allo-immunisation, et surtout de surcharge martiale, difficilement accessible ensuite au traitement médicamenteux chélateurPARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Dépistage néonatal de la drépanocytose en France

International audienceLe dépistage néonatal de la drépanocytose, la plus fréquente des maladies rares en France, a permis, entre 1984 et 2019, l’identification de 9 260 nouveau-nés atteints de drépanocytose (dont 586 en 2019) et de 180 687 hétérozygotes AS. Ce dépistage a permis la mise en œuvre précoce de mesures prophylactiques chez ces enfants, grâce à un tissu sanitaire et social structuré. Depuis que ce dépistage est organisé, on a pu observer, dès l’âge pédiatrique, une diminution majeure de la mortalité et de la morbidité de la drépanocytose, qui concerne notamment les complications infectieuses invasives, anémiques et neuro-vasculaires. En métropole, ce dépistage garde la particularité d’être ciblé vers les nouveau-nés dont les parents sont originaires de régions à risque. La fréquence croissante de la drépanocytose (1/1 303 nouveau-nés identifiés en 2019 contre 1/2 089 en 2009) et l’augmentation de la fréquence des hétérozygotes plaident aujourd’hui pour un dépistage systématique étendu à tous les nouveau-nés et pour une meilleure information sur cette maladie, devenue un enjeu majeur de santé publique

Douleurs et souffrances de jeunes drépanocytaires en Île-de-France

La drépanocytose est une maladie génétique qui s’est développée dans les zones impaludées. Du fait de la traite négrière et de la migration, elle est maintenant présente dans les pays occidentaux et notamment en France. Cette pathologie présente la particularité de provoquer des douleurs atroces. Cet article cherche dans un premier temps à comprendre les sensations douloureuses de jeunes drépanocytaires franciliens de 18 à 26 ans dans toute leur singularité, mais aussi à identifier quelques invariants communs. Face à ces sensations douloureuses, les jeunes cherchent du sens à leur malheur. Aussi, dans un second temps, nous analysons leurs postures face à la souffrance, et notamment le recours aux dimensions religieuses. Le refuge auprès d’une ou plusieurs religions aide les jeunes à ne pas se laisser engloutir par la maladie, à se projeter dans un avenir meilleur, à s’inscrire dans une vie qui a un sens au sein d’une communauté spirituelle.Sickle cell anemia is a genetic disorder that originally emerged in regions of the world where malaria is endemic. With the spread of populations out of these regions because of the slave trade and migration, sickle cell disease is now present in Western countries including France. This pathology has the peculiarity of causing excruciating pain. This article first seeks to understand the painful sensations of Ile-de-France sickle cell patients aged 18 to 26 in all their particularity, while also identifying some common invariants. We then analyze young people’s attitudes towards their suffering and in particular their recourse to spirituality. Turning towards one or more religious traditions helps young people to surmount their illness, to plan for a better future, and to find a meaningful life in a spiritual community

Steroid treatment in children with sickle-cell disease.

Given the controversy concerning the effects of steroids in patients with sickle cell disease (SCD), we evaluated the tolerability of long-term steroid treatment in 16 children with SCD and autoimmune and/or systemic diseases. The steroid treatment was poorly tolerated.LetterMulticenter StudySCOPUS: ar.jinfo:eu-repo/semantics/publishe

Salbutamol Worsens the Autonomic Nervous System Dysfunction of Children With Sickle Cell Disease

International audienceBackground: Sickle cell disease (SCD) patients with asthma have an increased rate of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) episodes when compared to those without asthma. We hypothesized that either asthma diagnosis or bronchodilator treatment might aggravate SCD via their modulating effect on the autonomic nervous system (ANS).Methods: Cross-sectional evaluation of heart rate variability (HRV) during pulmonary function tests, including salbutamol administration, in children with SCD receiving asthma treatment or not when compared to asthmatic children without SCD matched for ethnicity.Results: SCD children with asthma (n = 30, median age of 12.9 years old) were characterized by a reduced FEV1/FVC ratio, an increased bronchodilator response, and a greater incidence of VOC and ACS when compared to SCD children without asthma (n = 30, 12.7 years). Children with asthma without SCD (n = 29, 11.4 years) were characterized by a higher exhaled NO fraction than SCD children. SCD children when compared to non-SCD children showed reduced HRV [total power, low (LF) and high (HF, vagal tone) frequencies], which was further worsened by salbutamol administration in all the groups: reduction in total power and HF with an increase in LF/HF ratio. After salbutamol, the LF/HF ratio of the SCD children was higher than that of the non-SCD children. The two groups of SCD children were similar, suggesting that asthma diagnosis per se did not modify ANS functions.Conclusion: SCD children are characterized by impaired parasympathetic control and sympathetic overactivity that is worsened by salbutamol administration.Clinical trial registration: www.ClinicalTrials.gov, identifier NCT04062409

Clinical and Translational Physiology, a section of the journal Frontiers in Physiology

International audienceBackground: Sickle cell disease (SCD) patients with asthma have an increased rate of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) episodes when compared to those without asthma. We hypothesized that either asthma diagnosis or bronchodilator treatment might aggravate SCD via their modulating effect on the autonomic nervous system (ANS).Methods: Cross-sectional evaluation of heart rate variability (HRV) during pulmonary function tests, including salbutamol administration, in children with SCD receiving asthma treatment or not when compared to asthmatic children without SCD matched for ethnicity.Results: SCD children with asthma (n = 30, median age of 12.9 years old) were characterized by a reduced FEV1/FVC ratio, an increased bronchodilator response, and a greater incidence of VOC and ACS when compared to SCD children without asthma (n = 30, 12.7 years). Children with asthma without SCD (n = 29, 11.4 years) were characterized by a higher exhaled NO fraction than SCD children. SCD children when compared to non-SCD children showed reduced HRV [total power, low (LF) and high (HF, vagal tone) frequencies], which was further worsened by salbutamol administration in all the groups: reduction in total power and HF with an increase in LF/HF ratio. After salbutamol, the LF/HF ratio of the SCD children was higher than that of the non-SCD children. The two groups of SCD children were similar, suggesting that asthma diagnosis per se did not modify ANS functions.Conclusion: SCD children are characterized by impaired parasympathetic control and sympathetic overactivity that is worsened by salbutamol administration

Hétérogénéité génotypique du déficit en G6PD à l’Ouest de l’Afrique Sub-saharienne

abstract: Hématologie 2000; 6(HS):45info:eu-repo/semantics/nonPublishe

Variability of Prognostic Results Based on Biological Parameters in Sickle Cell Disease Cohort Studies in Children: What Should Clinicians Know?

Background: Many pediatric studies describe the association between biological parameters (BP) and severity of sickle cell disease (SCD) using different methods to collect or to analyze BP. This article assesses the methods used for collection and subsequent statistical analysis of BP, and how these impact prognostic results in SCD children cohort studies. Methods: Firstly, we identified the collection and statistical methods used in published SCD cohort studies. Secondly, these methods were applied to our cohort of 375 SCD children, to evaluate the association of BP with cerebral vasculopathy (CV). Results: In 16 cohort studies, BP were collected either once or several times during follow-up. The identified methods in the statistical analysis were: (1) one baseline value per patient (2) last known value; (3) mean of all values; (4) modelling of all values in a two-stage approach. Applying these four different statistical methods to our cohort, the results and interpretation of the association between BP and CV were different depending on the method used. Conclusion: The BP prognostic value depends on the chosen statistical analysis method. Appropriate statistical analyses of prognostic factors in cohort studies should be considered and should enable valuable and reproducible conclusions