Storia naturale, gestione e genetica della sindrome da infezione ricorrente da iperimmunoglobulina E (HIES)
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.
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Descrizione dettagliata
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.
Tipo di studio
Tipo di studio
Iscrizione (Stimato)
Iscrizione
Contatti e Sedi
Contatto studio
Contatto studio
- Nome: Jean M Ulrick
- Numero di telefono: (301) 221-0855
- Email: julrick@niaid.nih.gov
Luoghi di studio
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Maryland
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Bethesda, Maryland, Stati Uniti, 20892
- Reclutamento
- National Institutes of Health Clinical Center
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Contatto:
- For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
- Numero di telefono: TTY dial 711 800-411-1222
- Email: ccopr@nih.gov
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Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Metodo di campionamento
Popolazione di studio
primary clinical
Descrizione
- INCLUSION CRITERIA:
Patients may be included in this study who:
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Were referred to the NIH with a diagnosis or a suspicion of Hyper IgE syndrome.
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Are patients referred for other immune syndromes that demonstrate some of the characteristics of HIES.
- >=1 month for affected subjects
- Aged >=2 years for unaffected subjects
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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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Modelli osservazionali: COHORT
- Prospettive temporali: PROSPECTIVE
Numero di gruppi/coorti
Coorti e interventi
Gruppo / CoorteGruppo / Coorte |
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Affected adults and children
Confirmed or suspected history of a Hyper IgE syndrome |
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Relatives
Family members of subjects with confirmed or suspected history of a Hyper IgE syndrome |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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To clinically phenotype AD-HIES, DOCK8 deficiency, PGM3 deficiency and other related hyper IgE syndromes
Lasso di tempo: end of study
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established clinical phenotype of AD-HIES, DOCK8 deficiency, PGM3 deficiency and other related hyper IgE syndromes |
end of study
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To assess quality of life on the basis of clinical and immunologic evaluations
Lasso di tempo: end of study
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quality of life assessments based on clinical and immunologic evaluations |
end of study
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To understand the pathogenesis of the immunologic defect in hyper IgE syndromes as well as the diverse clinical features such as wound healing abnormalities
Lasso di tempo: end of study
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understanding of the pathogenesis of the immunologic defect in hyper IgE syndromes as well as the diverse clinical features such as wound healing abnormalities |
end of study
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To identify, characterize, and treat complications of the hyper IgE syndromes as they arise
Lasso di tempo: end of study
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identification, characterization, and treatment of complications of the hyper IgE syndromes |
end of study
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To identify novel genetic defects leading to hyper IgE syndromes.
Lasso di tempo: end of study
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identified novel genetic defects leading to hyper IgE syndromes. |
end of study
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Collaboratori e investigatori
Sponsor
Sponsor
Collaboratori
Collaboratori
Investigatori
Investigatori
- Investigatore principale: Alexandra F Freeman, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Pubblicazioni e link utili
Pubblicazioni generali
- 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, Schaffer 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.
- 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.
- 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.
- Freeman AF, Holland SM. Clinical manifestations of hyper IgE syndromes. Dis Markers. 2010;29(3-4):123-30. doi: 10.3233/DMA-2010-0734.
- 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.
- 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.
- Freeman AF, Wang C, Urban A, Martin I, Dang L, Davis J, Bergerson JRE, Ali S, An ZA, Patel M, Williamson H, Marciano BE, Lafeer C, Roy S, Ulrick J, Heller T, Sharma D, Castelo-Soccio L, Cowen EW, Kong HH, Gupta S, Ghosh R, Seifert BA, Tokita MJ, Walkiewicz MA, Similuk M, Stoddard J, Rosenzweig SD, Matta JR, Gharib AM, Jahanmir G, Brenchley L, Shastri K, Moutsopoulos NM, Kitani T, Arnold DE, Dimitrova D, Gonzalez CE, Pai SY, Malech HL, Gallin JI, Fennelly K, Olivier KN, Mackie J, Tangye SG, Hsu AP, Milner JD, Heimall J, Holland SM. Clinical features, genetics, treatment, and long-term outcomes of STAT3 hyper-IgE syndrome: Single-center cohort analysis. J Allergy Clin Immunol. 2026 Apr 28:S0091-6749(26)00292-7. doi: 10.1016/j.jaci.2026.04.012. Online ahead of print.
Collegamenti utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Inizio studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stimato)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie da immunodeficienza primaria
- Malattie genetiche, congenite
- Infezioni delle vie respiratorie
- Malattie delle vie respiratorie
- Malattie polmonari
- Disturbi dei leucociti
- Malattie ematologiche
- Disfunzione battericida dei fagociti
- Malattie e anomalie congenite, ereditarie e neonatali
- Malattie emiche e linfatiche
- Polmonite
- Infezioni
- Sindromi da deficit immunologico
- Malattie del sistema immunitario
- Sindrome da lavoro
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- 000159
- 00-I-0159
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
We will share human data generated in this study for future research as follows:@@@@@@@@@@@@Identified data in the Biomedical Translational Research Information System (BTRIS, automatic for activities in the NIH CC)@@@@@@@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements@@@@@@@@@@@@Data will be shared through: @@@@@@@@@@@@BTRIS (automatic for activities in the NIH CC)@@@@@@@@@@@@Approved outside collaborators under appropriate individual agreements@@@@@@@@@@@@Publication and/or public presentations.@@@@@@@@@@@@Data might be shared before publication.
Periodo di condivisione IPD
IPD is available in real time in BTRIS.
Criteri di accesso alla condivisione IPD
Identified data in the Biomedical Translational Research Information System (BTRIS, automatic for activities in the NIH CC) are available indefinitely.@@@@@@@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- ICF
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
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