The Potential and Limits of Hematopoietic Stem Cell Transplantation for the Treatment of Autosomal Dominant Hyper-IgE Syndrome.

PURPOSE: Autosomal dominant hyper-IgE syndrome (AD-HIES) is included among primary immunodeficiencies, and results from heterozygous mutations in the signal transduction and activator of transcription 3 (STAT3) gene. AD-HIES leads to impaired Th17 cell differentiation and IL-17 production, and is associated with increased susceptibility to bacteria and fungi. It was reported that several patients with AD-HIES were treated with hematopoietic stem cell transplantation (HSCT). The efficacy of HSCT in treating AD-HIES is variable. This study aims to evaluate the long-term clinical and immunological efficacy of HSCT for AD-HIES.

METHODS

We have followed for more than 8 years two patients with AD-HIES who were treated with HSCT. Their ability of IL-17 production was evaluated by flow cytometry.

RESULTS

Both patients indicated the normal ability of IL-17 production and their serum IgE levels decreased after HSCT. On the other hand, they suffered from pulmonary complications of AD-HIES such as pneumatoceles and bronchiectasis even after HSCT; however, the frequency of infections was decreased.

CONCLUSIONS

Although the dysfunction of STAT3 in non-hematological tissues such as the lungs could not be corrected by HSCT, AD-HIES patients with risk factors for pulmonary complications may benefit from immunological correction by HSCT before severe pulmonary complications occur. Future studies should investigate risk factors for pulmonary complications in AD-HIES patients.