Abstract
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.
Similar content being viewed by others
References
Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature. 2007;448:1058–62.
Farmand S, Sundin M. Hyper-IgE syndromes: recent advances in pathogenesis, diagnostics and clinical care. Curr Opin Hematol. 2015;22:12–22.
Freeman AF, Kleiner DE, Nadiminti H, Davis J, Quezado M, Anderson V, et al. Causes of death in hyper-IgE syndrome. J Allergy Clin Immunol. 2007;119:1234–40.
Worth AJ, Booth C, Veys P. Stem cell transplantation for primary immune deficiency. Curr Opin Hematol. 2013;20:501–8.
Gennery AR, Flood TJ, Abinun M, Cant AJ. Bone marrow transplantation does not correct the hyper IgE syndrome. Bone Marrow Transplant. 2000;25:1303–5.
Goussetis E, Peristeri I, Kitra V, Traeger-Synodinos J, Theodosaki M, Psarra K, et al. Successful long-term immunologic reconstitution by allogeneic hematopoietic stem cell transplantation cures patients with autosomal dominant hyper-IgE syndrome. J Allergy Clin Immunol. 2010;126:392–4.
Nester TA, Wagnon AH, Reilly WF, Spitzer G, Kjeldsberg CR, Hill HR. Effects of allogeneic peripheral stem cell transplantation in a patient with job syndrome of hyperimmunoglobulinemia E and recurrent infections. Am J Med. 1998;105:162–4.
Patel NC, Gallagher JL, Torgerson TR, Gilman AL. Successful haploidentical donor hematopoietic stem cell transplant and restoration of STAT3 function in an adolescent with autosomal dominant hyper-IgE syndrome. J Clin Immunol. 2015;35:479–85.
Steward-Tharp SM, Laurence A, Kanno Y, Kotlyar A, Villarino AV, Sciume G, et al. A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3. Blood. 2014;123:2978–87.
Zhang LY, Tian W, Shu L, Jiang LP, Zhan YZ, Liu W, et al. Clinical features, STAT3 gene mutations and Th17 cell analysis in nine children with hyper-IgE syndrome in mainland China. Scand J Immunol. 2013;78:258–65.
Choi SM, McAleer JP, Zheng M, Pociask DA, Kaplan MH, Qin S, et al. Innate Stat3-mediated induction of the antimicrobial protein Reg3gamma is required for host defense against MRSA pneumonia. J Exp Med. 2013;210:551–61.
Cho JS, Pietras EM, Garcia NC, Ramos RI, Farzam DM, Monroe HR, et al. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest. 2010;120:1762–73.
Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L, et al. Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey. Medicine (Baltimore). 2012;91:e1–19.
Wolach O, Kuijpers T, Ben-Ari J, Gavrieli R, Feinstein-Goren N, Alders M, et al. Variable clinical expressivity of STAT3 mutation in hyperimmunoglobulin E syndrome: genetic and clinical studies of six patients. J Clin Immunol. 2014;34:163–70.
Slatter MA, Rao K, Amrolia P, Flood T, Abinun M, Hambleton S, et al. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood. 2011;117:4367–75.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Yanagimachi, M., Ohya, T., Yokosuka, T. et al. The Potential and Limits of Hematopoietic Stem Cell Transplantation for the Treatment of Autosomal Dominant Hyper-IgE Syndrome. J Clin Immunol 36, 511–516 (2016). https://doi.org/10.1007/s10875-016-0278-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10875-016-0278-1