Glocker Erik, Ehl Stephan, Grimbacher Bodo
Department of Immunology and Molecular Pathology, University College London Royal Free Hospital, London, UK.
Curr Opin Pediatr. 2007 Dec;19(6):685-92. doi: 10.1097/MOP.0b013e3282f1ddd5.
Common variable immunodeficiency is the most common primary immunodeficiency that needs medical attention. Symptoms may occur at any time, with two major peaks of onset at 5-10 and 20-30 years. We present the different clinical phenotypes of common variable immunodeficiency, review recent genetic findings and point to current treatment strategies.
Five genes, ICOS, CD19, TNFRSF13B, TNFRSF13C and MSH5, have been found to be mutated in patients with common variable immunodeficiency. Additional possible genetic loci for autosomal dominant forms were detected on chromosomes 4q and 16q. These findings illustrate the heterogeneous molecular basis of common variable immunodeficiency and indicate the value of genetic linkage studies, thereby improving the genetic diagnosis.
In young patients with unusually frequent bacterial infections, common variable immunodeficiency should always be considered as a differential diagnosis. The compulsory individual work-up should comprise a family history in order to document siblings and additional family members suffering from common variable immunodeficiency and/or selective IgA deficiency. Since the recently found gene defects affect a minority of patients with common variable immunodeficiency only, future genetic research is required to identify further susceptibility genes involved in the pathogenesis of this condition.
普通变异型免疫缺陷是最常见的需要医疗关注的原发性免疫缺陷。症状可在任何时候出现，发病有两个主要高峰，分别在5至10岁和20至30岁。我们介绍普通变异型免疫缺陷的不同临床表型，回顾近期的遗传学发现，并指出当前的治疗策略。
已发现五个基因，即ICOS、CD19、TNFRSF13B、TNFRSF13C和MSH5，在普通变异型免疫缺陷患者中发生突变。在4号染色体和16号染色体上检测到常染色体显性形式的其他可能基因位点。这些发现说明了普通变异型免疫缺陷的分子基础具有异质性，并表明了基因连锁研究的价值，从而改善了基因诊断。
对于细菌感染异常频繁的年轻患者，应始终将普通变异型免疫缺陷作为鉴别诊断考虑。强制性的个体检查应包括家族史，以记录患有普通变异型免疫缺陷和/或选择性IgA缺乏症的兄弟姐妹及其他家庭成员。由于最近发现的基因缺陷仅影响少数普通变异型免疫缺陷患者，因此需要未来的基因研究来确定参与该疾病发病机制的其他易感基因。
