LE DEFICIT IMMUNITAIRE COMMUN VARIABLE (A PROPOS DE 6 CAS)

Common variable immunodeficiency (CVID) is a constitutional deficit in the antibody. It can be of transmission recessive, dominating or related to X. The CVID is the only being able to appear at the adulthood. The fundamental cause of this disorder remains unknown. The disease is characterized by the heterogeneity of the clinical picture and the immunological characteristic Our study’s goal is to present un discuss 6 cases of CVID hospitalized at the clinical Immunology Unit, of the Pediatry I department in the child hospital of Casablanca, between March 1998 and March 2004. The mean age at the first clinical symptoms is 11 years. Our six patients, suffered from recurrent pneumonias, the recurrent sinusitis, the chronic diarrhea with failure to thrive and granulomatous disease. They all had a hypogammaglobulinemia, the taking in charge consisted in an infections episode treatment as well as a nutrition rehabilitation with intravenous immunoglobulin antibiotic prophylaxis and a respiratory kinesitherapy. Our set was characterized by the severity of the clinical phenotype, especially by the therapeutic means insufficiency, and the delay of the diagnostic. A considerable effort should be achieved in order to make doctors more sensitive, tools of diagnosis and the hold in charge.Le déficit immunitaire commun variable (DICV) est un déficit primitif en anticorps, de transmission récessive, dominante ou liée à l’X, et qui peut se révéler à l’âge adulte. Son mécanisme moléculaire est encore inconnu. Le diagnostic est caractérisé par une hétérogénéité du tableau clinique et immunologique. L’objectif de notre travail est de présenter et discuter 6 cas de DICV, hospitalisés à l’unité d’immunologie clinique de la Pédiatrie I à l’hôpital d’Enfants de Casablanca, sur 6 ans (1998 – 2004). L’âge moyen de début des symptômes est de 11 ans. Nos 6 malades avaient présenté des broncho-pneumopathies à répétitions, des infections ORL, des diarrhées chroniques avec retentissement staturo-pondéral, et un cas de sarcoïdose. Ils avaient présenté tous une hypogammaglobulinémie globale. La prise en charge a consisté en un traitement des épisodes infectieux, une perfusion des immunoglobulines, une antibioprophylaxie et une kinésithérapie respiratoire. Le tableau clinique de nos malades reste sévère du fait du retard du diagnostic et de l’insuffisance des moyens thérapeutiques ; c’est pourquoi un effort doit être réalisé, afin de sensibiliser les médecins, pour établir un diagnostic précoce et une prise en charge adéquate

A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity.

Heterozygosity for human () dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the promoter. The patients\u27 cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with DN mutations, ZNF341-deficient patients lack T helper 17 (T17) cells, have an excess of T2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the transcription-dependent autoinduction and sustained activity of STAT3

A novel homozygous p.R1105X mutation of the AP4E1 gene in twins with hereditary spastic paraplegia and mycobacterial disease.

We report identical twins with intellectual disability, progressive spastic paraplegia and short stature, born to a consanguineous family. Intriguingly, both children presented with lymphadenitis caused by the live Bacillus Calmette-Guérin (BCG) vaccine. Two syndromes - hereditary spastic paraplegia (HSP) and mycobacterial disease - thus occurred simultaneously. Whole-exome sequencing (WES) revealed a homozygous nonsense mutation (p.R1105X) of the AP4E1 gene, which was confirmed by Sanger sequencing. The p.R1105X mutation has no effect on AP4E1 mRNA levels, but results in lower levels of AP-4ε protein and of the other components of the AP-4 complex, as shown by western blotting, immunoprecipitation and immunofluorescence. Thus, the C-terminal part of the AP-4ε subunit plays an important role in maintaining the integrity of the AP-4 complex. No abnormalities of the IL-12/IFN-γ axis or oxidative burst pathways were identified. In conclusion, we identified twins with autosomal recessive AP-4 deficiency associated with HSP and mycobacterial disease, suggesting that AP-4 may play important role in the neurological and immunological systems

Déficits immunitaires primitifs: approche diagnostique pour les pays émergents

International audiencePrimary immunodeficiencies (PIDs) correspond to various genetic diseases characterized by a heterogeneous clinical expression in children and a frequent revelation in adults Faced to clinical suspicion of an immune deficiency, the existence of syndrome features may evoke defined PID entities that need specific immunological analysis Otherwise, the diagnostic approach of PID requires four steps the first one is to rule out an acquired immune deficiency mainly HIV infection The second step is based on elementary biological investigations cell blood count, measure of G, A, and M immunoglobulins combined or not to protein electrophoresis, and an assessment of total hemolytic complement This line of analysis permit to discriminate cellular, humoral, phagocytic or complement deficiencies which can be further illustrated using specialized immunological investigations such as lymphocyte subpopulations phenotyping, quantification of immunoglobulin subclasses, detection of specific antibodies, T lymphocytes proliferation assay, nitroblue tetrazolium reduction (NBT) test, CD18 phenotyping, measure of C3 and C4 complement components The last step needs collaboration with genetic research laboratories in order to establish the genotype of the immunodeficiency (C) 2010 Elsevier Masson SAS All rights reservedLes déficits immunitaires primitifs (DIP) correspondent à environ 300 maladies génétiques actuellement connues, d’expression clinique hétérogène se révélant parfois tardivement chez l’adulte. Devant la suspicion d’un déficit immunitaire, la présence de signes syndromiques permet d’emblée d’évoquer des entités de DIP bien définies nécessitant un bilan étiologique spécifique. Sinon, dans l’optique d’optimiser les moyens exploratoires, la mise en évidence d’un DIP impose une démarche diagnostique en étapes. La première étape vise surtout à éliminer un déficit immunitaire acquis notamment, une infection à VIH ; la deuxième étape repose sur un bilan biologique de base (numération formule sanguine-plaquette, dosage des immunoglo-bulines [IgG, IgA, IgM] et/ou électrophorèse des protides, étude du complément hémolytique CH50). Confronté à la clinique, ce bilan initial permettra de distinguer quatre catégories de déficits : cellulaire, humoral, phagocytaire ou du complément pour lesquels la troisième étape grâceà des explorations immunologiques spécialisées (étude des sous-populations lymphocytaires, dosage des sous-classes d’Ig, recherche d’anticorps spécifiques, tests de prolifération lymphoctaire, test au NBT, étude phénotypique de CD18, dosage des fractions du complément... ) permettra de confirmer le DIP et de préciser sa nature. Enfin, la quatrième étape sera menée en collaboration avec des laboratoires de recherche spécialisés pour déterminer le type moléculaire du déficit

The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies

© 2015 Springer Science+Business Media New York There are now nearly 300 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. For each of these five categories, a g