Bethesda, Maryland 20892

  • Job Syndrome

Purpose:

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 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.


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.


NCT ID:

NCT00006150


Primary Contact:

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

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


Backup Contact:

Email: freemaal@mail.nih.gov
Alexandra Freeman, M.D.
Phone: (301) 594-9045


Location Contact:

Bethesda, Maryland 20892
United States

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone: 800-411-1222
Email: prpl@cc.nih.gov

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: March 30, 2020

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