Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome.

BACKGROUND: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic veno-occlusive disease. OBJECTIVES: We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin. METHODS: Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells. RESULTS: We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels. Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell-dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function. CONCLUSION: These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population.

Novel and recurrent STAT3 mutations in hyper-IgE syndrome patients from different ethnic groups.

We performed clinical, immunological and genetic studies of 12 hyper-IgE syndrome (HIES) patients from 4 Hungarian, 2 Lebanese, one Russian, one Polish, and one Swedish families with autosomal dominant (AD) or sporadic forms of the disease to reveal cross-ethnicity of recurrent and novel mutations in the signal transducer and activator of transcription-3 gene (STAT3). Four patients from 3 Hungarian families, and one Russian, and one Swedish patient carried the heterozygous R382W germline mutation at the DNA-binding site of STAT3. The recurrent V637M mutation affecting the SRC homology 2 (SH2) domain was detected in one Lebanese and one Polish family, and the V463del deletion located in the DNA-binding domain was unveiled in another Lebanese family. A novel H332Y mutation affecting the DNA-binding site of STAT3 in three Hungarian patients from a Gypsy family was also found. The segregation of this mutation with HIES, restriction fragment length polymorphism analysis of STAT3 from patients and controls and the negligible production upon IL-6 stimulation of monocyte chemotactic protein-1 by the patient's blood mononuclear cells suggested that the H332Y mutation was disease-causing. These data suggest, that dominant negative mutations of the DNA-binding and SH2 domains of STAT3 cause AD and sporadic cases of HIES in different ethnic groups with R382W as the predominant mutation found in 5 of the 9 families. Functional and genetic data support that the novel H332Y mutation may result in the loss of function of STAT3 and leads to the HIES phenotype.

Effects of a prethickened formula on esophageal pH and gastric emptying of infants with GER.

OBJECTIVE(S): Advantages of prethickened formulas (AR) with regards to esophageal pH and gastric emptying were investigated in this study as compared with a regular formula (R). STUDY DESIGN: Seventy-four healthy infants, <6 months old, with gastroesophageal reflux were enrolled into the study. All infants underwent 24-hour esophageal pH monitoring while receiving R and AR, alternately. Electrogastrography was measured before and after feeding each study formula. Thereafter, the infants were randomly assigned to receive either R or AR for 1 month. Episodes of regurgitation, vomiting, coughing, crying, and bowel movements were recorded on a weekly interval. RESULTS: Reflux index (RI) of AR-fed infants were lower (5.64%) than the R-fed infants (7.77%) showing a significant difference (P<0.01) between the 2 groups, favoring AR. Eighty-seven percent of infants improved their RI while receiving the AR formula. Electrogastrography variables were not significantly different between the 2 study groups. A significant decrease (P<0.01) in the daily episodes of regurgitation and vomiting was observed in the AR-fed infants. No adverse events were reported during the study. CONCLUSIONS: Prethickened infant formula was effective in reducing clinical symptoms of uncomplicated gastroesophageal reflux and reducing RI. Prethickened formulas do not alter gastric emptying time and was very well tolerated.

[Children of the war]. / Les enfants de la guerre.

Children are always concerned by wars. Physical consequences (death, severe wounds, disability) are surely important, but physiological trauma can also be grave. We studies the impact of war on two groups of children aged between 6 and 10 years. The first group consisted of children living in Lebanon during the war, and the second was composed of children born in Paris of Lebanese migrant parents.

[Acute asthma attack in children presenting to the emergency department. Survey of 96 cases]. / La crise d'asthme de l'enfant aux urgences: enquête sur 96 cas.

Throughout a 2-year period, children who presented at Hôtel-Dieu de France emergency department (ED) with acute asthma were analyzed prospectively and data on their environment, family and personal history as well as treatment were recorded. Treatment delivered at the ED, response and further outcome were analyzed. Out of 2024 children aged less than 15 years, 96 (5%) had acute asthma attack. Their median age was 4 years and M/F ratio was 2:1. Median age at onset of asthma was 2 years. Only 66 patients were recognized as asthmatics and 20% were given regular inhaled daily treatment. Current attack was mild in 45%, moderate in 45% and severe in 10% of cases. Home treatment before ED admission was often inadequate. Nine patients required hospital admission after failure of treatment at the ED. Within a median follow-up of 12 months, half of the patients experienced further attacks sometimes requiring ED care (27%) or hospital admission (8%). These data highlight the fact that asthma in our country is still largely under recognized and inadequately treated.