title: Hyper-IgE syndromes: recent advances in pathogenesis, diagnostics and clinical care.
abstract: OBJECTIVE
  This review provides an overview on recent data regarding pathogenesis, diagnostics and clinical care of hyper-IgE syndromes (HIES). HIES are a group of primary immunodeficiencies with overlapping and distinct features, most frequently caused by deficiency in signal transducer and activator of transcription 3 (STAT3) or dedicator of cytokinesis 8 (DOCK8).
  
  
  RESULTS
  Particular progress has been made in deciphering the relevance of STAT3 and DOCK8 for B-cell, T-cell and natural killer-cell immunity as well as in understanding allergic features. Multisystemic features of STAT3-deficient HIES, for example, recurrent fractures and osteopenia, a high degree of vasculopathy and brain white matter hyperintensities, have been thoroughly characterized. IgG replacement may add to the clinical care in STAT3-deficient HIES. In DOCK8-deficient HIES, the high morbidity and deaths in early age seem to justify allogeneic hematopoietic stem cell transplantation. New HIES entities have also been reported.
  
  
  CONCLUSIONS
  The recent advances expand our understanding of HIES, and improve the diagnostics and clinical care. Yet, more research is required to fully elucidate the specific infection susceptibilities and lung complications, particularly in STAT3-deficient HIES. Future studies also need to focus on clinical care and treatment of nonimmunologic features of HIES, as well as on exploring curative treatments.
authors.affiliation: aDepartment of Microbiology, Tumor and Cell Biology bDivision of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet cSection of Hematology, Immunology and HSCT, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Susan
authors.initials: S
authors.lastname: Farmand
authors.forename: Mikael
authors.initials: M
authors.lastname: Sundin
mesh_terms: D064591:Allografts; D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007589:Job Syndrome / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D050796:STAT3 Transcription Factor / Q000235:genetics*
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human