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Study of Clinical Features and Genetics of Hyperimmunoglobulin E Recurrent Infection

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ClinicalTrials.gov Identifier: NCT00006150
Recruitment Status : Recruiting
First Posted : August 9, 2000
Last Update Posted : October 4, 2019
Sponsor:
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) )

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-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.

Condition or disease
Osteopenia Scoliosis Airway Disease Eczema Aneurysmal Coronary Artery Disease

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.

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Study Type : Observational
Estimated Enrollment : 500 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





Primary Outcome Measures :
  1. To clinically phenotype AD- HIES, DOCKS deficiency, PGM3 deficiency and other related hyper IgE syndromes [ Time Frame: end of study ]
    established clinical phenotype of AD-HIES, DOCKS deficiency, PGM3 deficiency and other related hyper IgE syndromes

  2. 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

  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 suchas wound healing abnormalities

  4. To identify novel genetic defects leading to hyper IgE syndromes. [ Time Frame: end of study ]
    identified novel genetic defects leading to hyper IgE syndromes.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
primary clinical
Criteria
  • INCLUSION CRITERIA:

Patients must be referred to the NIH with a diagnosis or a suspicion of Hyper IgE syndrome. Family members of probands and patients referred for other immune syndromes that demonstrate some of the characteristics of HIES may also be evaluated under this protocol. Male and female patients will be accepted. An inclusion age range will be constructed to accommodate at-risk infants born into affected families as well as to be able to examine the members of extended families. The extent of evaluation will be tailored to the patient s needs, age, and conditions. The cutaneous manifestations of Hyper IgE syndromes are often present at birth and need management from that time on.

EXCLUSION CRITERIA:

Pregnant women are excluded only from any procedure or test that may endanger the pregnancy or the fetus due to the risk from radiographic studies, anesthesia, or certain biopsies. We have seen flares of skin disease during pregnancy and therefore believe that enrolling and following these patients during pregnancy is appropriate.

Coronary CTA will not be performed on any patient 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006150


Contacts
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Contact: Christine J Lafeer, R.N. (301) 761-6902 clafeer@niaid.nih.gov
Contact: Alexandra Freeman, M.D. (301) 594-9045 freemaal@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike 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 TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Albert Einstein College of Medicine
Investigators
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Principal Investigator: Alexandra Freeman, M.D. National Institute of Allergy and Infectious Diseases (NIAID)

Additional Information:
Publications:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00006150     History of Changes
Other Study ID Numbers: 000159
00-I-0159
First Posted: August 9, 2000    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: September 25, 2019
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
Hyperimmunologobulin E Syndrome
HIE Syndrome
Additional relevant MeSH terms:
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Scoliosis
Bone Diseases, Metabolic
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Spinal Curvatures
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases