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

• ClinicalTrials.gov Identifier: NCT00006150
• Recruitment Status: Recruiting
• First Posted: August 9, 2000
• Last Update Posted: May 25, 2023
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Albert Einstein College of Medicine
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Study Description

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.

Condition or disease
Infections; Pneumonia; Immune System Diseases; STAT3 Transcription Factor; Job Syndrome

Detailed Description:

The Hyper IgE Syndromes (HIES) are primary immunodeficiencies resulting in eczema and recurrent skin and lung infections. Autosomal dominant Hyper IgE syndrome (AD-HIES; 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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 600 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)
• Actual Study Start Date: August 10, 2000

Groups and Cohorts

Group/Cohort
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

Outcome Measures

Primary Outcome Measures :

1. To clinically phenotype AD-HIES, DOCK8 deficiency, PGM3 deficiency and other related hyper IgE syndromes [ Time Frame: end of study ]
   established clinical phenotype of AD-HIES, DOCK8 deficiency, PGM3 deficiency and other related hyper IgE syndromes
2. To assess quality of life on the basis of clinical and immunologic evaluations [ Time Frame: end of study ]
   quality of life assessments based on clinical and immunologic evaluations
3. To understand the pathogenesis of the immunologic defect in hyper IgE syndromes as well as the diverse clinical features such as wound healing abnormalities [ Time Frame: end of study ]
   understanding of the pathogenesis of the immunologic defect in hyper IgE syndromes as well as the diverse clinical features such as wound healing abnormalities
4. To identify, characterize, and treat complications of the hyper IgE syndromes as they arise [ Time Frame: end of study ]
   identification, characterization, and treatment of complications of the hyper IgE syndromes
5. To identify novel genetic defects leading to hyper IgE syndromes. [ Time Frame: end of study ]
   identified novel genetic defects leading to hyper IgE syndromes.

Eligibility Criteria

• Ages Eligible for Study: 1 Month and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

primary clinical

Criteria

• INCLUSION CRITERIA:

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.
• Are male or female, aged

Aged

• >=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.

EXCLUSION CRITERIA:

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.

Contacts and Locations

Contacts

Contact: Christine J Lafeer, R.N.; (301) 761-6902; clafeer@niaid.nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY dial 711 ccopr@nih.gov

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Albert Einstein College of Medicine

Investigators

• Principal Investigator: Alexandra F Freeman, M.D.; National Institute of Allergy and Infectious Diseases (NIAID)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00006150
• Other Study ID Numbers: 000159; 00-I-0159
• First Posted: August 9, 2000
• Last Update Posted: May 25, 2023
• Last Verified: May 19, 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: .We will share human data generated in this study for future research as follows:@@@@@@Identified data in the Biomedical Translational Research Information System (BTRIS, automatic for activities in the NIH CC)@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements@@@@@@Data will be shared through: @@@@@@BTRIS (automatic for activities in the NIH CC)@@@@@@Approved outside collaborators under appropriate individual agreements@@@@@@Publication and/or public presentations.@@@@@@Data might be shared before publication.
• Supporting Materials: Study Protocol; Informed Consent Form (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

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

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

Additional relevant MeSH terms:

Infections; Communicable Diseases; Job Syndrome; Immune System Diseases; Syndrome; Reinfection; Disease; Pathologic Processes; Disease Attributes; Recurrence; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes