TACI is mutant in common variable immunodeficiency and IgA deficiency
TACI is mutant in common variable immunodeficiency and IgA deficiency
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DOI：
10.1038/ng1601
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发表时间：
2005-08-01
期刊：
影响因子：
30.8
通讯作者：
Geha, RS
中科院分区：
文献类型：
--
作者：
Castigli, E;Wilson, SA;Geha, RS
肿瘤坏死因子受体家族成员TACI（跨膜激活剂和钙调节性和亲环蛋白配体相互作用因子）介导B细胞的同型转换。我们发现19名无亲和关系的常见可变免疫缺陷（CVID）患者中有4名和16名IgA缺乏（IgAD）患者中有1名在TNFRSF13B的一个等位基因（编码TACI）上有错义突变。四名CVID患者中有一人在另一个TNFRSF13B等位基因中有一个核苷酸插入。这些突变在50名健康受试者中均未出现。在我们研究的四个指数个体的家庭成员中，TNFRSF13B突变与CVID或IgAD表型共分离。TACI突变个体的B细胞对TACI配体APRIL表达TACI，但不产生IgG和IgA，可能反映了同型转换受损。这些结果表明TACI突变可导致CVID和IgAD。
The tumor necrosis factor receptor family member TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. We found that 4 of 19 unrelated individuals with common variable immunodeficiency (CVID) and 1 of 16 individuals with IgA deficiency (IgAD) had a missense mutation in one allele of TNFRSF13B (encoding TACI). One of the four individuals with CVID had a single nucleotide insertion in the other TNFRSF13B allele. None of these mutations were present in 50 healthy subjects. TNFRSF13B mutations cosegregated with the phenotype of CVID or IgAD in family members of four index individuals that we studied. B cells from individuals with TACI mutations expressed TACI but did not produce IgG and IgA in response to the TACI ligand APRIL, probably reflecting impaired isotype switching. These results suggest that TACI mutations can result in CVID and IgAD.