Study of Clinical Features and Genetics of Hyperimmunoglobulin E Recurrent Infection
Study of Clinical Features and Genetics of Hyperimmunoglobulin E Recurrent Infection
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.
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.
-  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:

 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.