Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

Autosomal Dominant Hyper IgE Syndrome

  • Jenna R. E. Bergerson
  • Alexandra F. FreemanEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_168-1



Autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES)(OMIM#147060), also known as Job’s syndrome, is a primary immunodeficiency characterized by elevated immunoglobulin E (IgE), eczema, infections, and multiple connective tissue, skeletal, and vascular abnormalities. First described in 1966 by Davis et al., it was initially characterized by the triad of eosinophilia, eczema, and recurrent skin and pulmonary infections (Davis et al. 1966). Shortly thereafter, in 1972, Buckley et al. recognized that an elevated IgE levels was a part of this clinical spectrum, giving rise to the name hyperimmunoglobulin E syndrome. Dominant-negative heterozygous mutations in signal transducer and activator of transcription 3 (STAT3) were identified in 2007 as the link between recurrent infections and connective tissue abnormalities (Holland et al. 2007; Minegishi et al. 2007). Many cases are sporadic, but when familial, all...

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  1. Abd-Elmoniem KZ, Ramos N, Yazdani SK, Ghanem AM, Holland SM, Freeman AF, et al. Coronary atherosclerosis and dilation in hyper IgE syndrome patients: depiction by magnetic resonance vessel wall imaging and pathological correlation. Atherosclerosis. 2017;258:20–5.  https://doi.org/10.1016/j.atherosclerosis.2017.01.022.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Arora M, Bagi P, Strongin A, Heimall J, Zhao X, Lawrence MG, et al. Gastrointestinal manifestations of STAT3-deficient hyper IgE syndrome. J Clin Immunol. 2017;37(7):695–700.  https://doi.org/10.1007/s10875-017-0429-z.CrossRefPubMedGoogle Scholar
  3. Davis SD, Schaller J, Wedgwood RJ. Job’s syndrome. Recurrent, “cold,” staphylococcal abscesses. Lancet. 1966;1(7445):1013–5.CrossRefGoogle Scholar
  4. Freeman AF, Olivier KN. Hyper IgE syndromes and the lung. Clin Chest Med. 2016;37(3):557–67.  https://doi.org/10.1016/j.ccm.2016.4.016.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Goussetis E, Peristeri I, Kitra V, Traeger-Synodinos J, Theodosaki M, Osarra K, et al. Successful long-term immunologic reconstitution by allogenic hematopoietic stem cell transplantation cures patients with autosomal dominant hyper-IgE syndrome. J Allergy Clin Immunol. 2010;126(2):392–4.  https://doi.org/10.1016/j.jaci.2010.05.005.CrossRefPubMedGoogle Scholar
  6. Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, et al. STAT3 mutations in the hyper IgE syndrome. N Engl J Med. 2007;357(16):1608–19.  https://doi.org/10.1056/NEJMoa073687.CrossRefPubMedGoogle Scholar
  7. Hox V, O’Connell MP, Lyons J, Sackstein P, Dimaggio T, Jones N, et al. Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis. J Allergy Clin Immunol. 2016;138(1):187–99.  https://doi.org/10.1016/j.jaci.2015.11.024.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 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(7157):1058–62.  https://doi.org/10.1038/nature06096.CrossRefGoogle Scholar
  9. Siegel AM, Heimall J, Freeman AF, Hsu AP, Brittain E, Brenchley JM, et al. A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory. Immunity. 2011;35(5):806–18.  https://doi.org/10.1016/j.immuni.2011.09.016.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012;1250:25–32.  https://doi.org/10.1111/j.1749-6632.2011.06387.x.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Yanagimachi M, Ohya T, Yokosuka T, Kajiwara R, Tanaka F, Goto H, et al. The potential and limits of hematopoietic stem cell transplantation for the treatment of autosomal dominant hyper-IgE syndrome. J Clin Immunol. 2016;36(5):511–6.  https://doi.org/10.1007/s10875-016-0278-1.CrossRefPubMedGoogle Scholar
  12. Yong PF, Freeman AF, Engelhardt KR, Holland SM, Puck JM, Grimbacher B. An update on the hyper-IgE syndromes. Arthritis Res Ther. 2012;14(6):228.  https://doi.org/10.1186/ar4069.CrossRefPubMedPubMedCentralGoogle Scholar

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Authors and Affiliations

  • Jenna R. E. Bergerson
    • 1
  • Alexandra F. Freeman
    • 1
    Email author
  1. 1.Laboratory of Clinical Immunology and MicrobiologyNational Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)BethesdaUSA

Section editors and affiliations

  • Jolan Walter
    • 1
  1. 1.USF HealthTampaUSA