Poodt A E J, Driessen G J A, de Klein A, van Dongen J J M, van der Burg M, de Vries E
Department of Pediatrics, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
Clin Exp Immunol. 2009 Apr;156(1):35-9. doi: 10.1111/j.1365-2249.2008.03863.x. Epub 2008 Dec 11.
The most prevalent primary immunodeficiency is common variable immunodeficiency (CVID). Mutations have been described in four genes, ICOS, CD19, BAFF-R and TNFRSF13B (encoding TACI), together associated with 10-15% of CVID cases. We investigated a family with CVID and identified the heterozygous C104R TNFRSF13B mutation in two of the three index-children with CVID, a mother with selective immunoglobulin A deficiency, a mother with recurrent infections and a healthy grandfather. Remarkably, we did not find the TNFRSF13B mutation in the third index-child with CVID, despite his hypogammaglobulinaemia and decreased response to unconjugated pneumococcal vaccine. This family illustrates that TNFRSF13B mutations induce disease susceptibility rather than cause disease directly. Apparently, other genetic or environmental factors, still to be identified, contributed to the development of CVID in this family. Consequently, TNFRSF13B mutations must be interpreted with caution in the clinical setting.
最常见的原发性免疫缺陷是普通变异型免疫缺陷（CVID）。已在四个基因（ICOS、CD19、BAFF-R和TNFRSF13B，后者编码TACI）中发现了突变，这些基因共同与10%至15%的CVID病例相关。我们研究了一个患有CVID的家族，在三名患有CVID的索引儿童中的两名、一名患有选择性免疫球蛋白A缺乏症的母亲、一名患有反复感染的母亲以及一名健康的祖父中鉴定出杂合的C104R TNFRSF13B突变。值得注意的是，我们在第三名患有CVID的索引儿童中未发现TNFRSF13B突变，尽管他存在低丙种球蛋白血症且对未结合的肺炎球菌疫苗反应降低。这个家族表明，TNFRSF13B突变会诱发疾病易感性，而非直接导致疾病。显然，其他尚未确定的遗传或环境因素促成了该家族中CVID的发生。因此，在临床环境中对TNFRSF13B突变的解读必须谨慎。
