A defective V-kappa A2 allele in Navajos which play play a role in increased susceptibility to Haemophilus influenzae type disease
A defective V-kappa A2 allele in Navajos which play play a role in increased susceptibility to Haemophilus influenzae type disease
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DOI：
10.1172/jci118669
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发表时间：
1996-05-15
影响因子：
15.9
通讯作者：
Lugo, G
中科院分区：
文献类型：
--
作者：
Feeney, AJ;Atkinson, MJ;Lugo, G
抗体对H.流感病毒B型（HiB）是少克隆的，并且由使用V（k）A2基因的抗体控制。与对照人群相比，纳瓦霍人的Hib疾病发病率增加了5-10倍。我们假设，在这种寡克隆反应的基因之一的多态性可能会导致疾病的易感性增加。由于主要的A2（+）抗Hib抗体对Hib具有高亲合力并且可以是未突变的，所以分析A2 V-k基因。超过一半的被研究的纳瓦霍人，但只有一个对照个体，具有A2的新等位基因，称为A2 b，与公开的A2种系序列相比具有三个变化，其中一个变化是重组信号序列，提示A2 b等位基因可能不经常发生V-J重排。通过分析A2 a/B杂合子纳瓦霍人中非生产性A2重排的相对频率证实了这种可能性。观察到A2 b重排少得多，表明A2 b等位基因进行重排的能力有缺陷。这种等位基因在纳瓦霍人中的流行可能在他们对侵袭性Hib疾病的易感性增加中发挥作用。如果是这样的话，它将强调生殖系IG库的重要性，保护性抗体反应的病原菌在未免疫的儿童。
The antibody response to H. influenzae type b (Hib) is pauciclonal, and is dominated by antibodies using the V(k)A2 gene. Navajos have a 5-10-fold increased incidence of Hib disease compared with control populations. We hypothesized that a polymorphism in one of the genes in this oligoclonal response may lead to increased disease susceptibility. Since the predominant A2(+) anti-Hib antibodies have high avidity for Hib and can be unmutated, the A2 V-k gene was analyzed, Over half of the Navajos studied, but only one control individual, had a new allele of A2, termed A2b, with three changes from the published A2 germline sequence, One of the changes was in the recombination signal sequence, suggesting that the A2b allele might not undergo V-J rearrangement very frequently. This possibility was confirmed by analyzing the relative frequency of non-productive A2 rearrangements in A2a/b heterozygous Navajos. Many fewer A2b rearrangements were observed, showing that the A2b allele is defective in its ability to undergo rearrangement. The prevalence of this allele in Navajos may play a role in their increased susceptibility to invasive Hib disease. If so, it would underscore the importance of the germline Ig repertoire for protective antibody responses to pathogenic bacteria in unimmunized children.