title: Analysis of T-cell repertoire diversity in Wiskott-Aldrich syndrome.
abstract: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia, eczema, and variable degrees of impaired cellular and humoral immunity. Age-dependent T-cell lymphopenia has been described in WAS, however, the diversity of the T-cell compartment over time in these patients has not been characterized. We have used complementarity-determining region 3 (CDR3) size distribution analysis to assess T-cell receptor (TCR) Vbeta repertoire in 13 patients with WAS. Diverse CDR3 size pattern was demonstrated in patients under 15 years of age regardless of the levels of WAS protein (WASP) expression. In contrast, older patients showed significantly higher skewing of TCRVbeta repertoire as compared with healthy adults. We did not find correlation between clinical score and complexity of TCRVbeta repertoire. These findings suggest that WASP deficiency does not limit thymic generation of a normal TCR and indicate that T-cell oligoclonality may contribute to the immunodeficiency in older patients with WAS.
authors.affiliation: Genetics and Molecular Biology Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), 49 Convent Dr, Bldg 49, Rm 3A20, MSC 4442, Bethesda, MD 20892-4442, USA.
authors.forename: Taizo
authors.initials: T
authors.lastname: Wada
authors.forename: Shepherd H
authors.initials: SH
authors.lastname: Schurman
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Garabedian
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D022801:Complementarity Determining Regions / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology*
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta