PMID- 25079909
OWN - NLM
STAT- MEDLINE
DCOM- 20150112
LR  - 20220129
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 178
IP  - 3
DP  - 2014 Dec
TI  - A mutation in X-linked inhibitor of apoptosis (G466X) leads to memory inflation 
      of Epstein-Barr virus-specific T cells.
PG  - 470-82
LID - 10.1111/cei.12427 [doi]
AB  - Mutations in the X-linked inhibitor of apoptosis (XIAP) gene have been associated 
      with XLP-like disease, including recurrent Epstein-Barr virus (EBV)-related 
      haemophagocytic lymphohystiocytosis (HLH), but the immunopathogenic bases of 
      EBV-related disease in XIAP deficiency is unknown. We present the first analysis 
      of EBV-specific T cell responses in functional XIAP deficiency. In a family of 
      patients with a novel mutation in XIAP (G466X) leading to a late-truncated 
      protein and varying clinical features, we identified gradual 
      hypogammaglobulinaemia and large expansions of T cell subsets, including a 
      prominent CD4(+) CD8(+) population. Extensive ex-vivo analyses showed that the 
      expanded T cell subsets were dominated by EBV-specific cells with conserved 
      cytotoxic, proliferative and interferon (IFN)-gamma secretion capacity. The EBV load 
      in blood fluctuated and was occasionally very high, indicating that the 
      XIAP(G466X) mutation could impact upon EBV latency. XIAP deficiency may unravel a 
      new immunopathogenic mechanism in EBV-associated disease.
CI  - (c) 2014 British Society for Immunology.
FAU - Lopez-Granados, E
AU  - Lopez-Granados E
AD  - Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; 
      Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
FAU - Stacey, M
AU  - Stacey M
FAU - Kienzler, A-K
AU  - Kienzler AK
FAU - Sierro, S
AU  - Sierro S
FAU - Willberg, C B
AU  - Willberg CB
FAU - Fox, C P
AU  - Fox CP
FAU - Rigaud, S
AU  - Rigaud S
FAU - Long, H M
AU  - Long HM
FAU - Hislop, A D
AU  - Hislop AD
FAU - Rickinson, A B
AU  - Rickinson AB
FAU - Patel, S
AU  - Patel S
FAU - Latour, S
AU  - Latour S
FAU - Klenerman, P
AU  - Klenerman P
FAU - Chapel, H
AU  - Chapel H
LA  - eng
GR  - 091663/WT_/Wellcome Trust/United Kingdom
GR  - G0901755/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XIAP protein, human)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Cells, Cultured
MH  - Haplotypes
MH  - Herpesvirus 4, Human/*immunology
MH  - Humans
MH  - *Immunologic Memory
MH  - Interferon-gamma/biosynthesis
MH  - *Mutation
MH  - T-Lymphocytes/*immunology
MH  - Viral Load
MH  - X-Linked Inhibitor of Apoptosis Protein/*genetics
PMC - PMC4238874
OTO - NOTNLM
OT  - T cells
OT  - cytotoxic T cells
OT  - immunodeficiency diseases
OT  - viral
EDAT- 2014/08/01 06:00
MHDA- 2015/01/13 06:00
PMCR- 2015/12/01
CRDT- 2014/08/01 06:00
PHST- 2014/07/26 00:00 [accepted]
PHST- 2014/08/01 06:00 [entrez]
PHST- 2014/08/01 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1111/cei.12427 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2014 Dec;178(3):470-82. doi: 10.1111/cei.12427.