AUTHOR=O’Connell Amy E. , Volpi Stefano , Dobbs Kerry , Fiorini Claudia , Tsitsikov Erdyni , de Boer Helen , Barlan Isil B. , Despotovic Jenny M. , Espinosa-Rosales Francisco J. , Hanson I. Celine , Kanariou Maria G. , Martínez-Beckerat Roxana , Mayorga-Sirera Alvaro , Mejia-Carvajal Carmen , Radwan Nesrine , Weiss Aaron R. , Pai Sung-Yun , Lee Yu Nee , Notarangelo Luigi D. TITLE=Next Generation Sequencing Reveals Skewing of the T and B Cell Receptor Repertoires in Patients with Wiskott–Aldrich Syndrome JOURNAL=Frontiers in Immunology VOLUME=5 YEAR=2014 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2014.00340 DOI=10.3389/fimmu.2014.00340 ISSN=1664-3224 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.