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Front Immunol. 2018 Jan 18;8:1978. doi: 10.3389/fimmu.2017.01978. eCollection 2017.

Human NF-κB1 Haploinsufficiency and Epstein-Barr Virus-Induced Disease-Molecular Mechanisms and Consequences.

Hoeger B1,2, Serwas NK1,2, Boztug K1,2,3,4.

Author information

1
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.
2
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
3
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
4
Department of Pediatrics, St. Anna Kinderspital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria.

Abstract

Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1)-related human primary immune deficiencies have initially been characterized as defining a subgroup of common variable immunodeficiencies (CVIDs), representing intrinsic B-cell disorders with antibody deficiency and recurrent infections of various kind. Recent evidence indicates that NF-κB1 haploinsufficiency underlies a variable type of combined immunodeficiency (CID) affecting both B and T lymphocyte compartments, with a broadened spectrum of disease manifestations, including Epstein-Barr virus (EBV)-induced lymphoproliferative disease and immediate life-threatening consequences. As part of this review series focused on EBV-related primary immunodeficiencies, we discuss the current clinical and molecular understanding of monoallelic NFKB1 germline mutations with special focus on the emerging context of EBV-associated disease. We outline mechanistic implications of dysfunctional NF-κB1 in B and T cells and discuss the fatal relation of impaired T-cell function with the inability to clear EBV infections. Finally, we compare common and suggested treatment angles in the context of this complex disease.

KEYWORDS:

B cells; Epstein–Barr virus; T cells; combined immunodeficiency; common variable immunodeficiency; haploinsufficiency; lymphoproliferation; nuclear factor kappa-light-chain-enhancer of activated B cells 1

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