New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS.
New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS.
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DOI：
10.4049/jimmunol.162.11.6942
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发表时间：
1999-06
影响因子：
4.4
通讯作者：
H. Hendel;S. Caillat-Zucman;Hélène Lebuanec;M. Carrington;Stephen J. O’Brien;J. Andrieu;F. Schächter;D. Zagury;J. Rappaport;C. Winkler;G. Nelson;J. Zagury
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文献类型：
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作者：
H. Hendel;S. Caillat-Zucman;Hélène Lebuanec;M. Carrington;Stephen J. O’Brien;J. Andrieu;F. Schächter;D. Zagury;J. Rappaport;C. Winkler;G. Nelson;J. Zagury
抗HIV-1感染的遗传学队列由200名缓慢进展者和75名快速进展者组成，对应于20，000名欧洲血统白人的HIV疾病结局的极端情况。在这个信息量很大的队列中，对HLA I类和II类基因的综合分析已经确定了与快速或缓慢进展相关的HLA等位基因，包括先前未描述的几个等位基因。定量分析显示，总体HLA影响独立于CCR 5-Delta 32突变的影响，并且在程度上（对于保护作用）与CCR 5-Delta 32突变的影响相等。在HLA I类基因中，A29（p = 0.001）和B22（p < 0.0001）与快速进展显著相关，而B14（p = 0.001）和C8（p = 0.004）与非进展显著相关。I类等位基因B27、B57、C14（保护性）和C16，以及B35（易感性）也有影响，但它们的作用不太稳定。II类等位基因的影响仅观察到DR 11。这些结果证实了免疫系统对疾病进展的影响，并可能对基于肽的疫苗开发产生影响。
The genetics of resistance to infection by HIV-1 cohort consists of 200 slow and 75 rapid progressors to AIDS corresponding to the extremes of HIV disease outcome of 20,000 Caucasians of European descent. A comprehensive analysis of HLA class I and class II genes in this highly informative cohort has identified HLA alleles associated with fast or slow progression, including several not described previously. A quantitative analysis shows an overall HLA influence independent of and equal in magnitude (for the protective effect) to the effect of the CCR5-Delta32 mutation. Among HLA class I genes, A29 (p = 0.001) and B22 (p < 0.0001) are significantly associated with rapid progression, whereas B14 (p = 0.001) and C8 (p = 0.004) are significantly associated with nonprogression. The class I alleles B27, B57, C14 (protective), and C16, as well as B35 (susceptible), are also influential, but their effects are less robust. Influence of class II alleles was only observed for DR11. These results confirm the influence of the immune system on disease progression and may have implications on peptide-based vaccine development.