title: Successful haploidentical donor hematopoietic stem cell transplant and restoration of STAT3 function in an adolescent with autosomal dominant hyper-IgE syndrome.
abstract: OBJECTIVE
  Autosomal dominant hyper-IgE syndrome (AD-HIES), caused by mutations in Signal Transducer and Activator of Transcription 3 (STAT3) is associated with defective STAT3 signaling and Th17 differentiation and recurrent bacterial and fungal infections. Most patients suffer significant morbidity and premature mortality. Hematopoietic stem cell transplantation (HSCT) has been reported in a small number of cases, with mixed outcomes. We report successful haploidentical donor HSCT in a patient with AD-HIES.
  
  
  METHODS
  Evaluation of lymphocyte subsets, STAT3 signaling, and Th17 cells was performed pre- and post-HSCT.
  
  
  RESULTS
  A 14-year old female with AD-HIES developed recurrent methicillin-resistant Staphylococcus aureus (MRSA) abscesses. Immunologic analysis showed elevated IgE (4331 kU/L), absent Th17 cells, and markedly decreased STAT3 phosphorylation in cytokine stimulated peripheral blood mononuclear cells. She had breakthrough abscesses despite clindamycin and trimethoprim-sulfamethoxazole prophylaxis, and developed steroid refractory autoimmune hemolytic anemia. She underwent T-cell depleted haploidentical HSCT from her father following reduced intensity conditioning. She developed one MRSA hand abscess after transplant. Twenty-four months post transplant, she had complete donor chimerism (>95 % donor), normal absolute T cell numbers, and a normal percentage of Th17 cells. IgE was normal at 25 kU/L. She remains well 42 months after transplantation off all antibacterial prophylaxis.
  
  
  CONCLUSIONS
  Haploidentical HSCT led to successful bone marrow engraftment, normalization of STAT3 signaling in hematopoietic cells, normalization of IgE, and restoration of immune function in this patient with AD-HIES.
authors.affiliation: Department of Pediatrics, Section of Infectious Disease and Immunology, Levine Children's Hospital at Carolinas Medical Center, PO Box 32861, Charlotte, NC, 28203, USA, Niraj.Patel@carolinashealthcare.org.
authors.forename: N C
authors.initials: NC
authors.lastname: Patel
authors.forename: J L
authors.initials: JL
authors.lastname: Gallagher
authors.forename: T R
authors.initials: TR
authors.lastname: Torgerson
authors.forename: A L
authors.initials: AL
authors.lastname: Gilman
mesh_terms: D000293:Adolescent; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006801:Humans; D007239:Infections / Q000235:genetics / Q000276:immunology*; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology*; D009154:Mutation / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D058504:Th17 Cells / Q000276:immunology*; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D050796:STAT3 Transcription Factor