Sathkumara H D, De Silva N R, Handunnetti S, De Silva A D
Genetech Research Institute, Colombo, Sri Lanka.
Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka.
Int J Immunogenet. 2015 Aug;42(4):239-53. doi: 10.1111/iji.12217. Epub 2015 Jun 19.
Common variable immunodeficiency (CVID) is the most common clinically manifested primary immunodeficiency, which represents a heterogeneous group of hypogammaglobulinemias of largely unknown molecular defects. The hallmark of the disease is the elevated susceptibility to recurrent infections of respiratory and gastrointestinal tract, mainly due to encapsulated bacteria while a significant proportion of patients with CVID develop autoimmune and lymphoproliferative complications. The primary cause of CVID is still not known. However, a number of distinct genetic defects including in inducible co-stimulator (ICOS), B-cell-activating factor receptor (BAFFR) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) have been identified in a minority of patients with CVID. Mutations in tumour necrosis factor receptor superfamily (TNFRSF) member, TACI, are more frequently found to be associated to the disease in about 10% of patients with CVID, but may require additional immunologic defects for complete expression of the phenotype, as unaffected heterozygotes have also been described. Clinically, patients with TACI mutations could present with the complete spectrum of complications seen in CVID. Recent animal studies have provided substantial information on TACI signalling, yet it still offers an outstanding opportunity for further exploration of the aetiology, as a large part of it remains poorly understood. In this review, we aim at giving an insight into the genetics underlying the CVID and particularly at outlining the role of TACI and its relative contribution to the development of CVID-like phenotypes in human.
普通可变免疫缺陷（CVID）是临床上最常见的原发性免疫缺陷，它代表了一组异质性的低丙种球蛋白血症，其分子缺陷大多未知。该疾病的标志是呼吸道和胃肠道反复感染的易感性增加，主要是由于包膜细菌感染，而相当一部分CVID患者会出现自身免疫和淋巴增殖性并发症。CVID的主要病因仍然不明。然而，在少数CVID患者中已经发现了一些不同的基因缺陷，包括诱导性共刺激分子（ICOS）、B细胞活化因子受体（BAFFR）和跨膜激活剂、钙调蛋白和亲环素配体相互作用分子（TACI）。肿瘤坏死因子受体超家族（TNFRSF）成员TACI的突变在约10%的CVID患者中更常被发现与该疾病相关，但可能需要额外的免疫缺陷才能完全表达该表型，因为也有未受影响的杂合子被描述。临床上，TACI突变患者可能会出现CVID中所见的全部并发症。最近的动物研究提供了关于TACI信号传导的大量信息，但它仍然为进一步探索病因提供了一个绝佳机会，因为其中很大一部分仍然知之甚少。在这篇综述中，我们旨在深入了解CVID的遗传学基础，特别是概述TACI的作用及其对人类CVID样表型发展的相对贡献。
