Study of Clinical Features and Genetics of Hyperimmunoglobulin E Recurrent Infection

This study is currently recruiting participants.
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Albert Einstein College of Medicine of Yeshiva University
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00006150
First received: August 8, 2000
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

The study will evaluate patients with hyperimmunoglobulin E (HIE) recurrent infection in order to characterize the medical problems associated with this rare inherited disease, identify and treat complications, and do tests to identify the gene, or genes responsible for it. People with HIE have recurrent bacterial (staphylococcal) infections of the ears, sinuses, lungs or skin and elevated levels of the antibody immunoglobulin E. They may also have scoliosis (curvature of the spine), weak bones and recurrent bone fractures, strokes or other brain problems, severe itching and skin inflammation, and problems with baby teeth not falling out.

Patients of any age with HIE syndrome and their relatives may participate in this study. Patients will be evaluated by specialists in genetics, dermatology, bone metabolism, dental, radiology, neurology and immunology. Specific procedures may include the following:

  1. Medical history and physical examination
  2. Blood and urine collection for routine tests
  3. Blood collection for chromosome study, for DNA (genetic) testing and for growing certain cell lines that, with special care, will not die so they can be used for testing later
  4. Skin examination
  5. Family history interview with genetics specialists
  6. Neurology examination to test reflexes, strength, balance and movement
  7. Magnetic resonance imaging (MRI) of the brain
  8. Dental examination and X-rays, if needed, to look for abnormal loss or retention of baby teeth
  9. Computed tomography (CT) scan of the chest to examine the lungs
  10. Skeletal survey, including X-rays of the spine and several joints, bone densitometry (test to measure bone density), blood and urine tests to measure substances that indicate how fast new bone is made
  11. Pulmonary function test, using a breathing machine to see what volume of air the lungs can hold
  12. Skin biopsy (removal of small sample of skin tissue, under local anesthetic, for microscopic testing) for gene research purposes
  13. Bone biopsy (removal of small sample of bone tissue from the hip, under local anesthetic, for microscopic examination) for research on bone fractures

Patients will be followed once a year for five years. At each visit, they will have a MRI scan of the brain, CT scan of the chest, bone densitometry test, skin examination and dental examination. Patients with scoliosis will all have spine films.

Family members will have a physical examination, an interview with genetics specialists, and blood tests for cell counts, measurement of immunoglobulin E, and genetic studies. Some family members will also have cell lines made.


Condition
Job's Syndrome

Study Type: Observational
Official Title: Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 500
Study Start Date: August 2000
Detailed Description:

Hyper IgE Syndrome (HIE) is an autosomal dominant disorder caused primarily by STAT3 mutations with extensive skeletal and connective tissue manifestations. Whether STAT3 is the only genetic etiology remains unknown, as well as the etiology of related disorders, such as autosomal recessive Hyper IgE Syndrome. HIE affects a large number of tissues and functions, and is critical to our complete understanding of bone metabolism, bronchiectasis, dental maturation, and stroke. Therefore, we seek to enroll patients and families with a confirmed or suspected diagnosis of HIE 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 HIE and to be able to identify further genetic etiologies, as well as understand the pathogenesis of HIE. We seek to enroll 200 patients and 300 relatives.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Patients must be referred to the NIH with a diagnosis or a suspicion of Job Syndrome. Family members of probands and patients referred for other immune syndromes that demonstrate some the characteristics of Job's syndrome syndrome may also be evaluated under this protocol.

Male and female patients will be accepted.

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.

Coronary CT angiography will not be performed on any patient with contraindication to IV contrast media. This includes patients with: 1) creatinine value of greater than 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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006150

Contacts
Contact: Pamela A Welch, R.N. (301) 402-0449 welchp@mail.nih.gov
Contact: Steven M Holland, M.D. (301) 402-7684 sholland@mail.nih.gov

Locations
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 Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
Investigators
Principal Investigator: Steven M Holland, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00006150     History of Changes
Other Study ID Numbers: 000159, 00-I-0159
Study First Received: August 8, 2000
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
IgE
Fractures
Pneumonia
Scoliosis
Eczema
Job's Syndrome
Hyperimmunologobulin E Syndrome
HIE Syndrome

Additional relevant MeSH terms:
Job's Syndrome
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on April 16, 2014