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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: N/A

Referral Letter Required


Population Exclusion(s)


Special Instructions

Currently Not Provided


DOCK8 Deficiency;
PGM3 Deficiency;
STAT3 Mutation;
Job's Syndrome

Recruitment Keyword(s)

Job's Syndrome;
Hyperimmunologobulin E Syndrome;
HIE Syndrome


Coronary Aneurysm;
Dermatitis, Atopic;
Immune System Diseases;
STAT3 Transcription Factor;
Job 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 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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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.


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.

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Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb;1250:25-32. doi: 10.1111/j.1749-6632.2011.06387.x. Epub 2012 Jan 23.

Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, Miller JA, O'Connell AC, Puck JM. Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med. 1999 Mar 4;340(9):692-702.

Freeman AF, Holland SM. Clinical manifestations of hyper IgE syndromes. Dis Markers. 2010;29(3-4):123-30. doi: 10.3233/DMA-2010-0734.

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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

Christine J. Lafeer, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 3
Room 1W23
3 Center Drive
Bethesda, Maryland 20892
(301) 761-6902

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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