NCT00006150

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

Recruiting now Last updated 14 April 2026

What this trial tests

trial in Infections in 600 participants. Currently enrolling.

Timeline

10 August 2000

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	600
Start date	10 August 2000
Sites	1 location across United States

Conditions studied

• Infections — all drugs for Infections →
• Pneumonia — all drugs for Pneumonia →
• Immune System Diseases — all drugs for Immune System Diseases →
• STAT3 Transcription Factor — all drugs for STAT3 Transcription Factor →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 1 Month to 120, any sex, with Infections or Pneumonia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment.
   Zhang Y, Yu X, Ichikawa M, Lyons JJ, et al · · 2014 · cited 188× · PMID 24589341 · DOI 10.1016/j.jaci.2014.02.013
2. ERBIN deficiency links STAT3 and TGF-β pathway defects with atopy in humans.
   Lyons JJ, Liu Y, Ma CA, Yu X, et al · · 2017 · cited 77× · PMID 28126831 · DOI 10.1084/jem.20161435
3. Gastrointestinal Manifestations of STAT3-Deficient Hyper-IgE Syndrome.
   Arora M, Bagi P, Strongin A, Heimall J, et al · · 2017 · cited 55× · PMID 28803389 · DOI 10.1007/s10875-017-0429-z
4. A unified metric of human immune health.
   Sparks R, Rachmaninoff N, Lau WW, Hirsch DC, et al · · 2024 · cited 37× · PMID 38961223 · DOI 10.1038/s41591-024-03092-6
5. IL-10 Indirectly Downregulates IL-4-Induced IgE Production by Human B Cells.
   Lin AA, Freeman AF, Nutman TB. · · 2018 · cited 35× · PMID 31026808 · DOI 10.4049/immunohorizons.1800076
6. Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome.
   Dmitrieva NI, Walts AD, Nguyen DP, Grubb A, et al · · 2020 · cited 23× · PMID 32369445 · DOI 10.1172/jci135490
7. Lupus-like autoimmunity and increased interferon response in patients with STAT3-deficient hyper-IgE syndrome.
   Goel RR, Nakabo S, Dizon BLP, Urban A, et al · · 2021 · cited 20× · PMID 32768442 · DOI 10.1016/j.jaci.2020.07.024
8. Differential responses to folic acid in an established keloid fibroblast cell line are mediated by JAK1/2 and STAT3.
   McCann KJ, Yadav M, Alishahedani ME, Freeman AF, et al · · 2021 · cited 8× · PMID 33662027 · DOI 10.1371/journal.pone.0248011