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

作者：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; Martinez Beckerat Roxana; Mayorga Sirera Alvaro; Mejia Carvajal Carmen; Radwan Nesrine; Weiss Aaron R; Pai Sung Yun; Lee Yu Nee; Notarangelo Luigi D^*

来源：Frontiers in Immunology, 2014, 5: 340.

DOI：10.3389/fimmu.2014.00340

• Wiskott-Aldrich syndrome
• immune repertoire
• next generation sequencing
• deep sequencing
• B cell receptor
• T cell receptor
• somatic hypermutation
• clonotypic expansion

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 (3 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, naive and memory CDR 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.

• 出版日期2014-7-18