Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)

NCT00006150 | Recruiting

• 2 other identifiers: 00015900-I-0159
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

The Hyper IgE Syndromes (HIES) are primary immunodeficiencies resulting in eczema and recurrent skin and lung infections. Autosomal dominant Hyper IgE syndrome (AD-HIIES; Job's syndrome) is caused by STAT3 mutations, and is a multi-system disorder with skeletal, vascular, and connective tissue manifestations. Understanding how STAT3 mutations cause these diverse clinical manifestations is critical to our complete understanding of bone metabolism, bronchiectasis, dental maturation, and atherosclerosis. Bi-allelic mutations in DOCK8 cause a combined immunodeficiency previously described as autosomal-recessive Hyper IgE syndrome. These individuals suffer from extensive viral infections as well as have a high incidence of malignancy and mortality. The pathogenesis of this disease and long-term natural history is being investigated. Therefore, we seek to enroll patients and families with a confirmed or suspected diagnosis of HIES syndrome for extensive phenotypic and genotypic study as well as disease management. Patients will be carefully examined by a multidisciplinary team and followed longitudinally. Through these studies we hope to better characterize the clinical presentation of STAT3-mutated HIES, DOCK8 deficiency and other causes of the hyper IgE phenotype, and to be able to identify further genetic etiologies, as well as understand the pathogenesis of HIES. We seek to enroll 300 patients and 300 relatives.

Conditions

Pneumonia; Immune System Diseases; STAT3 Transcription Factor; Job Syndrome; Infections

Keywords

DOCK8 Deficiency; PGM3 Deficiency; STAT3 Mutation; Job's Syndrome; Immunodeficiency; Natural History; Hyperimmunologobulin E Syndrome; HIE Syndrome

Outcome Measures

Primary Outcomes (5)

• To clinically phenotype AD-HIES, DOCK8 deficiency, PGM3 deficiency and other related hyper IgE syndromes

  established clinical phenotype of AD-HIES, DOCK8 deficiency, PGM3 deficiency and other related hyper IgE syndromes

  end of study

• To assess quality of life on the basis of clinical and immunologic evaluations

  quality of life assessments based on clinical and immunologic evaluations

  end of study

• To understand the pathogenesis of the immunologic defect in hyper IgE syndromes as well as the diverse clinical features such as wound healing abnormalities

  understanding of the pathogenesis of the immunologic defect in hyper IgE syndromes as well as the diverse clinical features such as wound healing abnormalities

  end of study

• To identify, characterize, and treat complications of the hyper IgE syndromes as they arise

  identification, characterization, and treatment of complications of the hyper IgE syndromes

  end of study

• To identify novel genetic defects leading to hyper IgE syndromes.

  identified novel genetic defects leading to hyper IgE syndromes.

  end of study

Study Arms (2)

Affected adults and children

Confirmed or suspected history of a Hyper IgE syndrome

Relatives

Family members of subjects with confirmed or suspected history of a Hyper IgE syndrome

Eligibility Criteria

• Age: 1 Month - 120 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

primary clinical

You may qualify if:

• Patients may be included in this study who:
• Were referred to the NIH with a diagnosis or a suspicion of Hyper IgE syndrome.
• Are patients referred for other immune syndromes that demonstrate some of the characteristics of HIES.
• \>=1 month for affected subjects
• Aged \>=2 years for unaffected subjects
• For unaffected subjects, are able to understand and have the willingness to sign a written informed consent document.
• Unaffected biological relatives of HIES patients are also eligible to enroll in a separate relative cohort.

You may not qualify if:

• Coronary CTA will not be performed on any patient younger than 30 years or with contraindication to IV contrast media. This includes patients with 1) creatinine value of \>1.3 mg/dL, 2) history of multiple myeloma, 3) Use of metformin-containing products less than 24 hours prior to contrast media, and 4) history of significant allergic reaction to CT contrast agents despite the use of premedication.
• Subjects with a medical, psychiatric, or social condition which, in the opinion of the investigator, would place undue burden on the subject, NIH resources, or increase risk of participation, may be excluded.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Albert Einstein College of Medicine: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (6)

• Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb;1250:25-32. doi: 10.1111/j.1749-6632.2011.06387.x. Epub 2012 Jan 23.

  PMID: 22268731 BACKGROUND

• Freeman AF, Holland SM. Clinical manifestations of hyper IgE syndromes. Dis Markers. 2010;29(3-4):123-30. doi: 10.3233/DMA-2010-0734.

  PMID: 21178271 BACKGROUND

• Freeman AF, Avila EM, Shaw PA, Davis J, Hsu AP, Welch P, Matta JR, Hadigan C, Pettigrew RI, Holland SM, Gharib AM. Coronary artery abnormalities in Hyper-IgE syndrome. J Clin Immunol. 2011 Jun;31(3):338-45. doi: 10.1007/s10875-011-9515-9. Epub 2011 Apr 15.

  PMID: 21494893 BACKGROUND

• Freeman AF, Collura-Burke CJ, Patronas NJ, Ilcus LS, Darnell D, Davis J, Puck JM, Holland SM. Brain abnormalities in patients with hyperimmunoglobulin E syndrome. Pediatrics. 2007 May;119(5):e1121-5. doi: 10.1542/peds.2006-2649. Epub 2007 Apr 16.

  PMID: 17438082 BACKGROUND

• Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, Miller JA, O'Connell AC, Puck JM. Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med. 1999 Mar 4;340(9):692-702. doi: 10.1056/NEJM199903043400904.

  PMID: 10053178 BACKGROUND

• Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schaffer AA, Puck JM, Grimbacher B. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007 Oct 18;357(16):1608-19. doi: 10.1056/NEJMoa073687. Epub 2007 Sep 19.

  PMID: 17881745 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Infections; Pneumonia; Immune System Diseases; Job Syndrome; Immunologic Deficiency Syndromes

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Alexandra F Freeman, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean M Ulrick

CONTACT

(301) 221-0855; julrick@niaid.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2000
• First Posted: August 9, 2000
• Study Start: August 10, 2000
• Last Updated: May 1, 2026

Record last verified: 2026-03-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: IPD is available in real time in BTRIS.
• Access Criteria: Identified data in the Biomedical Translational Research Information System (BTRIS, automatic for activities in the NIH CC) are available indefinitely.@@@@@@@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements

Locations

US (1)