Hoeger Birgit, Serwas Nina Kathrin, Boztug Kaan
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Front Immunol. 2018 Jan 18;8:1978. doi: 10.3389/fimmu.2017.01978. eCollection 2017.
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 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.
活化B细胞的核因子κ轻链增强子1（NF-κB1）相关的人类原发性免疫缺陷最初被定义为常见可变免疫缺陷（CVID）的一个亚组，代表具有抗体缺陷和各种反复感染的内在B细胞疾病。最近的证据表明，NF-κB1单倍体不足是一种可变类型的联合免疫缺陷（CID）的基础，这种联合免疫缺陷会影响B和T淋巴细胞区室，具有更广泛的疾病表现谱，包括爱泼斯坦-巴尔病毒（EBV）诱导的淋巴增殖性疾病和直接危及生命的后果。作为这个专注于EBV相关原发性免疫缺陷的综述系列的一部分，我们讨论了目前对单等位基因种系突变的临床和分子理解，特别关注EBV相关疾病的新情况。我们概述了功能失调的NF-κB1在B细胞和T细胞中的机制影响，并讨论了T细胞功能受损与无法清除EBV感染之间的致命关系。最后，我们在这种复杂疾病的背景下比较了常见的和建议的治疗角度。
