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O'Connell AE, Volpi S, Dobbs K, et al. Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with wiskott-Aldrich syndrome. Front Immunol. 2014;5:340doi: 10.3389/fimmu.2014.00340.
O'Connell, A. E., Volpi, S., Dobbs, K., Fiorini, C., Tsitsikov, E., de Boer, H., Barlan, I. B., Despotovic, J. M., Espinosa-Rosales, F. J., Hanson, I. C., Kanariou, M. G., Martínez-Beckerat, R., Mayorga-Sirera, A., Mejia-Carvajal, C., Radwan, N., Weiss, A. R., Pai, S. Y., Lee, Y. N., & Notarangelo, L. D. (2014). Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with wiskott-Aldrich syndrome. Frontiers in immunology, 5340. https://doi.org/10.3389/fimmu.2014.00340
O'Connell, Amy E, et al. "Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with wiskott-Aldrich syndrome." Frontiers in immunology vol. 5 (2014): 340. doi: https://doi.org/10.3389/fimmu.2014.00340
O'Connell AE, Volpi S, Dobbs K, Fiorini C, Tsitsikov E, de Boer H, Barlan IB, Despotovic JM, Espinosa-Rosales FJ, Hanson IC, Kanariou MG, Martínez-Beckerat R, Mayorga-Sirera A, Mejia-Carvajal C, Radwan N, Weiss AR, Pai SY, Lee YN, Notarangelo LD. Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with wiskott-Aldrich syndrome. Front Immunol. 2014 Jul 18;5:340. doi: 10.3389/fimmu.2014.00340. eCollection 2014. PMID: 25101082; PMCID: PMC4102881.
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Front Immunol. 2014 Jul 18;5:340. doi: 10.3389/fimmu.2014.00340. eCollection 2014.

Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with wiskott-Aldrich syndrome.

Frontiers in immunology

Amy E O'Connell, Stefano Volpi, Kerry Dobbs, Claudia Fiorini, Erdyni Tsitsikov, Helen de Boer, Isil B Barlan, Jenny M Despotovic, Francisco J Espinosa-Rosales, I Celine Hanson, Maria G Kanariou, Roxana Martínez-Beckerat, Alvaro Mayorga-Sirera, Carmen Mejia-Carvajal, Nesrine Radwan, Aaron R Weiss, Sung-Yun Pai, Yu Nee Lee, Luigi D Notarangelo

Affiliations

  1. Department of Immunology, Boston Children's Hospital , Boston, MA , USA.
  2. Department of Hematology/Oncology, Boston Children's Hospital , Boston, MA , USA.
  3. Department of Laboratory Medicine, Boston Children's Hospital , Boston, MA , USA.
  4. Marmara University Medical Center , Istanbul , Turkey.
  5. Texas Children's Hospital , Houston, TX , USA.
  6. Instituto Nacional de Pediatría , Mexico City , Mexico.
  7. Aghia Sophia Children's Hospital , Athens , Greece.
  8. Department of Pediatric Hemato-Oncology, Hospital Mario Catarino Rivas , San Pedro Sula , Honduras.
  9. Centro de Neumologia y Alergia , San Pedro Sula , Honduras.
  10. Manati Medical Center, Manati , Puerto Rico, PR , USA.
  11. Ain Shams University , Cairo , Egypt.
  12. Maine Medical Center , Portland, ME , USA.
  13. Department of Immunology, Boston Children's Hospital , Boston, MA , USA ; Manton Center for Orphan Disease Research, Boston Children's Hospital , Boston, MA , USA.

PMID: 25101082 PMCID: PMC4102881 DOI: 10.3389/fimmu.2014.00340

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.

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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