期刊
CLINICAL IMMUNOLOGY
卷 161, 期 2, 页码 103-109出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2015.07.002
关键词
CID; ZAP70; SYK; TCR signaling; TREC newborn screening; Live vaccine adverse event
类别
资金
- INSERM
- ANR [ANR-08-MIEN-012-01, ANR-2010-MIDI-005-02, ANR-10-IAHU-01]
- Fondation ARC (France)
- European Research Council [ERC-2009-AdG_20090506, FP7-249816]
- German Research Council/DFG [HA5967/1-1, EXC294]
- German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung) [1 EO 0803]
- IMAGINE Foundation (MD/PhD-Programme)
- German Federal Ministry of Education and Research [BMBF 01EO1303, BMBF 1315883]
- ANR (France)
- Ligue contre le cancer (France)
Autosomal recessive human ZAP70 deficiency is a rare cause of combined immunodeficiency (CID) characterized by defective CD4 T cells and profound CD8 T cell lymphopenia. Herein, we report two novel patients that extend the molecular genetics, the clinical and functional phenotypes associated with the ZAP70 deficiency. The patients presented as infant-onset CID with severe infections caused by varicella zoster virus and live vaccines. Retrospective TCR excision circle newborn screening was normal in both patients. One patient carried a novel non-sense mutation (p.A495fsX75); the other a previously described misense mutation (p.A507V). In contrast to CD4 T cells, the majority of the few CD8 T cells showed expression of the ZAP70-related tyrosine kinase SYK that correlated with residual TCR signaling including calcium flux and degranulation. Our findings highlight the differential requirements of ZAP70 and SYK during thymic development, peripheral homeostasis as well as effector functions of CD4 and CD8 T cells. (C) 2015 Elsevier Inc. All rights reserved.
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