A mutation in X-linked inhibitor of apoptosis (G466X) leads to memory inflation of Epstein-Barr virus-specific T cells.

Journal article

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)-γ 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.

Authors: Lopez-Granados, E; Stacey, M; Kienzler, A; Sierro, S; Willberg, C

• Publication status: Published
• Publisher: Blackwell Publishing Ltd
• Journal: Clinical and experimental immunology
• Volume: 178
• Issue: 3
• Pages: 470-482
• Publication date: 2014-12-01
• DOI: 10.1111/cei.12427
• EISSN: 1365-2249
• ISSN: 0009-9104
• Language: English
• Keywords: Viral Load; Mutation; Haplotypes; Interferon-gamma; Cells, Cultured; immunodeficiency diseases; T cells; Immunologic Memory; X-Linked Inhibitor of Apoptosis Protein; cytotoxic T cells; T-Lymphocytes; Humans; Herpesvirus 4, Human; viral