Castigli Emanuela, Geha Raif S
Division of Immunology, Children's Hospital, Boston, Massachusetts 02115, USA.
J Allergy Clin Immunol. 2006 Apr;117(4):740-6; quiz 747. doi: 10.1016/j.jaci.2006.01.038.
Common variable immunodeficiency (CVID) is the most prevalent human primary immunodeficiency requiring medical attention. Until recently, the only known genetic defect specific to CVID was the inducible costimulatory receptor (ICOS) deficiency, which accounts for less than 1% of the patients. Recently, mutations in the TNF receptor family member transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), which mediates isotype switching in B cells, were found to be present in 10% to 20% of patients with CVID. Mutations in TACI were also found in relatives of patients with CVID who had IgA deficiency (IgAD), as well as in a patient with isolated IgAD. In the majority of patients described to date, only one TACI allele is mutated, showing an autosomal dominant transmission of the disease. B cells from individuals with TACI mutations did not produce IgG and IgA in response to the TACI ligand a proliferation-inducing ligand (APRIL), probably reflecting impaired isotype switching. These results suggest that TACI mutations can lead to CVID and IgAD.
常见变异型免疫缺陷（CVID）是最常见的需要医疗关注的人类原发性免疫缺陷。直到最近，唯一已知的CVID特异性基因缺陷是诱导性共刺激受体（ICOS）缺陷，其在患者中所占比例不到1%。最近发现，肿瘤坏死因子受体家族成员跨膜激活剂和钙调节剂及亲环素配体相互作用分子（TACI）发生突变，该分子介导B细胞的同种型转换，在10%至20%的CVID患者中存在。在患有IgA缺陷（IgAD）的CVID患者亲属以及一名孤立性IgAD患者中也发现了TACI突变。在迄今为止描述的大多数患者中，只有一个TACI等位基因发生突变，显示出该疾病的常染色体显性遗传。携带TACI突变个体的B细胞对TACI配体增殖诱导配体（APRIL）无反应，不产生IgG和IgA，这可能反映了同种型转换受损。这些结果表明，TACI突变可导致CVID和IgAD。
