title: Somatic mosaicism in B cells of a patient with autosomal dominant hyper IgE syndrome.
abstract: Hyper IgE syndrome (HIES) is characterized by recurrent skin abscesses, eczema, pneumonia, and high levels of serum IgE. Nonimmunologic manifestations of HIES include a characteristic face, pathologic dentition, scoliosis, bone alterations, hyperextensible joints, and vascular abnormalities. Somatic mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. In this report, we describe one patient with classical HIES and another patient with a mild phenotype, both harboring the same genetic mutation. The patient with a mild phenotype did not present the characteristic face, had normal production of IL-17A by T CD4+cells, but had low phosphorylation of STAT-3 in B cells. Interestingly, the mutation found in B cells was absent in other cell types analyzed, in agreement with the presence of a somatic mosaic genotype. The clinical and functional differences observed between these patients justify the use of complementary tools for a better definition of the cases. These approaches allow for a better understanding of complex phenotypes associated with somatic mosaicisms, and present the possibility to analyze the role of B lymphocytes in the pathophysiology of this disease. This knowledge has an impact on not only the treatment but also the provision of appropriate genetic counseling.
authors.affiliation: Department of Molecular Biomedicine, CINVESTAV-IPN, Mexico City, Mexico.|FES Zaragoza, National Autonomous University of Mexico, Mexico City.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Alcántara-Montiel
authors.affiliation: Hospital of High Specialties #25, IMSS, Monterrey, Nuevo Leon, Mexico.
authors.forename: Tamara
authors.initials: T
authors.lastname: Staines-Boone
authors.affiliation: Immunodeficiencies Research Unit, National Institute of Pediatrics, Mexico City.
authors.forename: Gabriela
authors.initials: G
authors.lastname: López-Herrera
authors.affiliation: Immunodeficiencies Research Unit, National Institute of Pediatrics, Mexico City.
authors.forename: Laura
authors.initials: L
authors.lastname: Berrón-Ruiz
authors.affiliation: Hospital of High Specialties #25, IMSS, Monterrey, Nuevo Leon, Mexico.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Borrego-Montoya
authors.affiliation: Department of Molecular Biomedicine, CINVESTAV-IPN, Mexico City, Mexico. lesantos@cinvestav.mx.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Santos-Argumedo
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005817:Genetic Counseling; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000378:metabolism; D007589:Job Syndrome / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D009928:Organ Specificity; D010641:Phenotype; D010766:Phosphorylation / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D058504:Th17 Cells / Q000502:physiology*; D055815:Young Adult
chemical_list: D020381:Interleukin-17; D050796:STAT3 Transcription Factor; D007073:Immunoglobulin E
keywords: Hyper IgE syndrome; IL-17A; STAT3 phosphorylation; Somatic mosaic