Abstract
ATM kinase modulates pathways implicated in premature ageing and ATM genotype predicts survival, yet immunodeficiency in ataxia telangiectasia is regarded as mild and unrelated to age. We address this paradox in a molecularly characterised sequential adult cohort with classical and mild variant ataxia telangiectasia. Immunodeficiency has the characteristics of premature ageing across multiple cellular and molecular immune parameters. This immune ageing occurs without previous CMV infection. Age predicts immunodeficiency in genetically homogeneous ataxia telangiectasia, and in comparison with controls, calendar age is exceeded by immunological age defined by thymic naive CD4+ T cell levels. Applying ataxia telangiectasia as a model of immune ageing, pneumococcal vaccine responses, characteristically deficient in physiological ageing, are predicted by thymic naive CD4+ T cell levels. These data suggest inherited defects of DNA repair may provide valuable insight into physiological ageing. Thymic naive CD4+ T cells may provide a biomarker for vaccine responsiveness in elderly cohorts. (C) 2011 Elsevier Inc. All rights reserved.
Original language | English |
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Pages (from-to) | 26-36 |
Number of pages | 11 |
Journal | Clinical Immunology |
Volume | 140 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jul 2011 |
Keywords
- Immune ageing
- Ataxia telangiectasia
- Naive T cells
- T cell receptor
- Pneumococcal antibodies
- ATM kinase