title: Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with wiskott-Aldrich syndrome.
abstract: The Wiskott-Aldrich syndrome (WAS) is due to mutations of the WAS gene encoding for the cytoskeletal WAS protein, leading to abnormal downstream signaling from the T cell and B cell antigen receptors (TCR and BCR). We hypothesized that the impaired signaling through the TCR and BCR in WAS would subsequently lead to aberrations in the immune repertoire of WAS patients. Using next generation sequencing (NGS), the T cell receptor β and B cell immunoglobulin heavy chain (IGH) repertoires of eight patients with WAS and six controls were sequenced. Clonal expansions were identified within memory CD4(+) cells as well as in total, naïve and memory CD8(+) cells from WAS patients. In the B cell compartment, WAS patient IGH repertoires were also clonally expanded and showed skewed usage of IGHV and IGHJ genes, and increased usage of IGHG constant genes, compared with controls. To our knowledge, this is the first study that demonstrates significant abnormalities of the immune repertoire in WAS patients using NGS.
authors.affiliation: Department of Immunology, Boston Children's Hospital , Boston, MA , USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: O'Connell
authors.affiliation: Department of Immunology, Boston Children's Hospital , Boston, MA , USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Volpi
authors.affiliation: Department of Immunology, Boston Children's Hospital , Boston, MA , USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Dobbs
authors.affiliation: Department of Hematology/Oncology, Boston Children's Hospital , Boston, MA , USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorini
authors.affiliation: Department of Laboratory Medicine, Boston Children's Hospital , Boston, MA , USA.
authors.forename: Erdyni
authors.initials: E
authors.lastname: Tsitsikov
authors.affiliation: Department of Hematology/Oncology, Boston Children's Hospital , Boston, MA , USA.
authors.forename: Helen
authors.initials: H
authors.lastname: de Boer
authors.affiliation: Marmara University Medical Center , Istanbul , Turkey.
authors.forename: Isil B
authors.initials: IB
authors.lastname: Barlan
authors.affiliation: Texas Children's Hospital , Houston, TX , USA.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Despotovic
authors.affiliation: Instituto Nacional de Pediatría , Mexico City , Mexico.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Espinosa-Rosales
authors.affiliation: Texas Children's Hospital , Houston, TX , USA.
authors.forename: I Celine
authors.initials: IC
authors.lastname: Hanson
authors.affiliation: Aghia Sophia Children's Hospital , Athens , Greece.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Kanariou
authors.affiliation: Department of Pediatric Hemato-Oncology, Hospital Mario Catarino Rivas , San Pedro Sula , Honduras.
authors.forename: Roxana
authors.initials: R
authors.lastname: Martínez-Beckerat
authors.affiliation: Centro de Neumologia y Alergia , San Pedro Sula , Honduras.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mayorga-Sirera
authors.affiliation: Manati Medical Center, Manati , Puerto Rico, PR , USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Mejia-Carvajal
authors.affiliation: Ain Shams University , Cairo , Egypt.
authors.forename: Nesrine
authors.initials: N
authors.lastname: Radwan
authors.affiliation: Maine Medical Center , Portland, ME , USA.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Weiss
authors.affiliation: Department of Hematology/Oncology, Boston Children's Hospital , Boston, MA , USA.
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Pai
authors.affiliation: Department of Immunology, Boston Children's Hospital , Boston, MA , USA.
authors.forename: Yu Nee
authors.initials: YN
authors.lastname: Lee
authors.affiliation: Department of Immunology, Boston Children's Hospital , Boston, MA , USA ; Manton Center for Orphan Disease Research, Boston Children's Hospital , Boston, MA , USA.
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
keywords: B cell receptor; T cell receptor; Wiskott–Aldrich syndrome; clonotypic expansion; deep sequencing; immune repertoire; next generation sequencing; somatic hypermutation
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