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

Summary

Number	00-I-0159
Sponsoring Institute	National Institute of Allergy and Infectious Diseases (NIAID)
Recruitment Detail	Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 1 mo Max Age: 120 Years
Referral Letter Required	No
Population Exclusion(s)	None
Keywords	DOCK8 Deficiency; PGM3 Deficiency; STAT3 Mutation; Job's Syndrome; Immunodeficiency; Natural History
Recruitment Keyword(s)	Job's Syndrome; Hyperimmunologobulin E Syndrome; HIE Syndrome
Condition(s)	Infections; Pneumonia; Immune System Diseases; STAT3 Transcription Factor; Job Syndrome
Investigational Drug(s)	None
Investigational Device(s)	None
Intervention(s)	None
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-HIIES; 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.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

Patients may be included in this study who:

-Were referred to the NIH with a diagnosis or a suspicion of Hyper IgE syndrome.

-Are patients referred for other immune syndromes that demonstrate some of the characteristics of HIES.

-Are male or female, aged

Aged

-- >=1 month for affected subjects

-- Aged >=2 years for unaffected subjects

-For unaffected subjects, are able to understand and have the willingness to sign a written informed consent document.

Unaffected biological relatives of HIES patients are also eligible to enroll in a separate relative cohort.

EXCLUSION CRITERIA:

Coronary CTA will not be performed on any patient younger than 30 years or 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.

--Back to Top--

Citations:

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. PMID: 22268731; PMCID: PMC4103910.

Freeman AF, Holland SM. Clinical manifestations of hyper IgE syndromes. Dis Markers. 2010;29(3-4):123-30. doi: 10.3233/DMA-2010-0734. PMID: 21178271; PMCID: PMC3835387.

Freeman AF, Avila EM, Shaw PA, Davis J, Hsu AP, Welch P, Matta JR, Hadigan C, Pettigrew RI, Holland SM, Gharib AM. Coronary artery abnormalities in Hyper-IgE syndrome. J Clin Immunol. 2011 Jun;31(3):338-45. doi: 10.1007/s10875-011-9515-9. Epub 2011 Apr 15. PMID: 21494893; PMCID: PMC4091041.

Freeman AF, Collura-Burke CJ, Patronas NJ, Ilcus LS, Darnell D, Davis J, Puck JM, Holland SM. Brain abnormalities in patients with hyperimmunoglobulin E syndrome. Pediatrics. 2007 May;119(5):e1121-5. doi: 10.1542/peds.2006-2649. Epub 2007 Apr 16. PMID: 17438082.

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. doi: 10.1056/NEJM199903043400904. PMID: 10053178.

Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Sch(SqrRoot) ffer AA, Puck JM, Grimbacher B. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007 Oct 18;357(16):1608-19. doi: 10.1056/NEJMoa073687. Epub 2007 Sep 19. PMID: 17881745.

--Back to Top--

Contacts:

Principal Investigator	Referral Contact	For more information:
Alexandra F. Freeman, M.D. National Institute of Allergy and Infectious Diseases (NIAID)	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 clafeer@niaid.nih.gov	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: TTY Users Dial 7-1-1 ccopr@nih.gov

Clinical Trials Number:

NCT00006150

--Back to Top--