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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 0
Max Age: 105

Referral Letter Required


Population Exclusion(s)


Special Instructions

Currently Not Provided



Recruitment Keyword(s)

Job's Syndrome;
Hyperimmunologobulin E Syndrome;
HIE Syndrome


Job's Syndrome

Investigational Drug(s)


Investigational Device(s)




Supporting Site

National Institute of Allergy and Infectious DiseasesAlbert Einstein School of Medicine

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 multisystem 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. Mutations in DOCK8 cause many cases of autosomalrecessive 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 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 HIES and to be able to identify further genetic etiologies, as well as understand the pathogenesis of HIES. We seek to enroll 200 patients and 300 relatives.

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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 HIE are often present at birth and need management from that time on.

Because this is often an AD disorder, it is important to evaluate family members. Family members will have labs drawn for genetic testing and additional labs as clinically indicated. Selected family members will have EBV cell lines made and all family members will receive a genetic-oriented physical examination with close examination of their palates, hyper-extensibility, etc. If on this evaluation any information is uncovered which suggests abnormalities related to Hyper IgE syndrome, then further workup would include chest X-ray or CT, possible spine films, dental evaluation, dermatology consult, and other consults or procedures deemed necessary for that particular relative. For the recessive forms of HIES, such as DOCK8 deficiency and PGM3 deficiency, family members may be evaluated as possible donors if a hematopoietic stem cell transplant is necessary.


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 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.

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Fatal histiocytic lymphoma of the brain associated with hyperimmunoglobulinemia-E and recurrent infections

Recurrent severe staphylococcal infections, eczematoid rash, extreme elevations of IgE, eosinophilia, and divergent chemotactic responses in two generations

Extreme hyperimmunoglobulin E and undue susceptibility to infection

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Principal Investigator

Referral Contact

For more information:

Alexandra Freeman, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
BG 10 RM 12C103
(301) 594-9045

Alexandra Freeman, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
BG 10 RM 12C103
(301) 594-9045

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010

Clinical Trials Number:


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