Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey.

Autosomal dominant deficiency of signal transducer and activator of transcription 3 (STAT3) is the main genetic etiology of hyper-immunoglobulin (Ig) E syndrome. We documented the molecular, cellular, and clinical features of 60 patients with heterozygous STAT3 mutations from 47 kindreds followed in France. We identified 11 known and 13 new mutations of STAT3. Low levels of interleukin (IL)-6-dependent phosphorylation and nuclear translocation (or accumulation) of STAT3 were observed in Epstein-Barr virus-transformed B lymphocytes (EBV-B cells) from all STAT3-deficient patients tested. The immunologic phenotype was characterized by high serum IgE levels (96% of the patients), memory B-cell lymphopenia (94.5%), and hypereosinophilia (80%). A low proportion of IL-17A-producing circulating T cells was found in 14 of the 15 patients tested. Mucocutaneous infections were the most frequent, typically caused by Staphylococcus aureus (all patients) and Candida albicans (85%). Up to 90% of the patients had pneumonia, mostly caused by Staph. aureus (31%) or Streptococcus pneumoniae (30%). Recurrent pneumonia was associated with secondary bronchiectasis and pneumatocele (67%), as well as secondary aspergillosis (22%). Up to 92% of the patients had dermatitis and connective tissue abnormalities, with facial dysmorphism (95%), retention of decidual teeth (65%), osteopenia (50%), and hyperextensibility (50%). Four patients developed non-Hodgkin lymphoma. The clinical outcome was favorable, with 56 patients, including 43 adults, still alive at the end of study (mean age, 21 yr; range, 1 mo to 46 yr). Only 4 patients died, 3 from severe bacterial infection (aged 1, 15, and 29 yr, respectively). Antibiotic prophylaxis (90% of patients), antifungal prophylaxis (50%), and IgG infusions (53%) improved patient health, as demonstrated by the large decrease in pneumonia recurrence. Overall, the prognosis of STAT3 deficiency may be considered good, provided that multiple prophylactic measures, including IgG infusions, are implemented.

Influence of previous antimicrobial therapy on oral carriage of beta-lactamase producing Capnocytophaga isolates.

AIM: In order to assess the prevalence of beta-lactamase producing oral bacteria in childhood, the influence of different parameters on the oral carriage of Capnocytophaga was studied in a specific population of children with cancer. The examined parameters included clinical observation of oropharyngeal mucosa, type of malignant disease and intake of chemotherapy and antimicrobial treatment. METHODS: The gingival and mucosal status of the patients was recorded before each sampling procedure. Samples were collected by oropharyngeal swabbing in children with leukaemia or other oncological diseases for isolation of Capnocytophaga strains. RESULTS: Capnocytophaga strains were more often isolated in samples from children with oncological diseases (71%) other than leukaemia (57%). Concomitant chemotherapy had no influence on oral Capnocytophaga carriage. A significant decrease of the prevalence of Capnocytophaga strains isolated was observed in children who received antimicrobial treatment within 8 days before the sampling procedure (15.5% vs. 28%). But, the incidence of beta-lactamase-producing strains was not linked to previous antimicrobial treatments. CONCLUSION: Oral carriage of Capnocytophaga strains can be linked to haematological disease and previous antibiotherapy, but results did not confirm that beta-lactamase treatments exert a selective pressure. Other factors might be involved in emerging for oral beta-lactamase-producing Capnocytophaga strains.