OC1 Clinical and molecular features of twenty children with hyper-IgE syndrome caused by stat3 gene mutation in mainland china

Background and aims STAT3 gene mutation causes autosomal dominant hyper- IgE syndrome (AD-HIES)is a rare primary immunodeficiency disease. We described the clinical and molecular features of 20 AD-HIES patients in Mainland China. Methods We diagnosed patients with AD-HIES on the basis of NIH score of ≥40 points, described the clinical features, sequenced the STAT3 gene of 20 patients, and quantified Th17 cells in peripheral blood of 19 patients by flow cytometry. Results Among the 20 patients (14 males and 6 females), the onset age ranged from 1 days to 6 months, and the diagnostic age ranged from 1 to 12 years. All patients (100%) had characteristic manifestation of HIES with the range of NIH scores 41–77 points, including recurrent eczema and pneumonia, particularly high serum IgE levels and eosinophilia. Characteristic facial features (100%), bone abnormalities, recurrent skin abscesses (85%), lung abscesses (60%), recurrent oral thrush (55%) were also present in the studied patients. STAT3 hot mutations V637M or R382W/Q were identified in 12 patients (60%), two novel heterozygous missense mutations (T620S and R609G) were identifiedin 2 patients respectively, and other mutations (C712G, S636F, Q469H, Y705H, V432M, c.1139+5G>T) were identified in other 6 patients. The percentage of Th17 cells in CD4+ T cells (CD3+CD8IL-17A+/CD3+CD8 cells) of 19 patients with STAT3 mutation was significantly decreased or deficient as compared with healthy controls. Conclusions Children with repeated Staphylococcus aureus pneumonia, cold skin abscess, fungal infection, eczema, increased serum IgE level and eosinophil, should be alert to AD-HIES. Detection of Th17 cell by flow cytometry assist clinical diagnosis when the NIH score ≥40 points. Further STAT3 gene analysis can confirmed the diagnosis.Early diagnosis and active prevention of infection can significantly improve the quality of life of patients.