Historia natural, manejo y genética del síndrome de infección recurrente por hiperinmunoglobulina 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....
Descripción general del estudio
Estado
Descripción detallada
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 de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Jean M Ulrick
- Número de teléfono: (301) 221-0855
- Correo electrónico: julrick@niaid.nih.gov
Ubicaciones de estudio
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Maryland
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Bethesda, Maryland, Estados Unidos, 20892
- Reclutamiento
- National Institutes of Health Clinical Center
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Contacto:
- For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
- Número de teléfono: TTY dial 711 800-411-1222
- Correo electrónico: ccopr@nih.gov
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
primary clinical
Descripción
- 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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: COHORT
- Perspectivas temporales: PROSPECTIVE
Cohortes e Intervenciones
Grupo / Cohorte |
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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 |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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To clinically phenotype AD-HIES, DOCK8 deficiency, PGM3 deficiency and other related hyper IgE syndromes
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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.
Periodo de tiempo: end of study
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identified novel genetic defects leading to hyper IgE syndromes. |
end of study
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Colaboradores e Investigadores
Colaboradores
Investigadores
- Investigador principal: Alexandra F Freeman, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimado)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades de inmunodeficiencia primaria
- Enfermedades Genéticas Congénitas
- Infecciones del Tracto Respiratorio
- Enfermedades de las vías respiratorias
- Enfermedades pulmonares
- Trastornos de los leucocitos
- Enfermedades hematológicas
- Disfunción bactericida de fagocitos
- Enfermedades y anomalías congénitas, hereditarias y neonatales
- Enfermedades hemic y linfáticas
- Neumonía
- Infecciones
- Síndromes de deficiencia inmunológica
- Enfermedades del sistema inmunológico
- Síndrome de trabajo
Otros números de identificación del estudio
- 000159
- 00-I-0159
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan 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.
Marco de tiempo para compartir IPD
IPD is available in real time in BTRIS.
Criterios de acceso compartido de 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 de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- CIF
Información sobre medicamentos y dispositivos, documentos del estudio
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