普姆瓦尼性工作者队列中人类白细胞抗原I类与HIV-1血清转化速率及疾病进展的关联

HLA class I associations with rates of HIV-1 seroconversion and disease progression in the Pumwani Sex Worker Cohort.

作者信息

Peterson T A, Kimani J, Wachihi C, Bielawny T, Mendoza L, Thavaneswaran S, Narayansingh M J, Kariri T, Liang B, Ball T B, Ngugi E N, Plummer F A, Luo M

机构信息

HIV and Human Genetics, National Microbiology Laboratory, Winnipeg, MB, Canada.

出版信息

Tissue Antigens. 2013 Feb;81(2):93-107. doi: 10.1111/tan.12051.

DOI:10.1111/tan.12051

PMID:23330720

Abstract

Class I human leukocyte antigens (HLA) play an important role in the adaptive immune response by presenting antigens to CD8+ T cells. Studies have reported that several HLA class I alleles are associated with differential disease progression in human immunodeficiency virus (HIV)-infected individuals, however, few class I associations with resistance or susceptibility to HIV-1 infection have been reported. We typed HLA-A, -B and -C of >1000 women enrolled in the Pumwani Sex Worker Cohort using a sequence-based typing method. Kaplan-Meier analysis was used to identify alleles influencing seroconversion and disease progression to acquired immune deficiency syndrome (CD4 < 200/mm³). A01 (P = 0.020), C06:02 (P = 0.042) and C07:01 (P = 0.050) are independently associated with protection from seroconversion. Women with any of these alleles are less likely to seroconvert [P = 0.00001, odds ratio (OR): 0.503, 95% confidence interval (CI): 0.320-0.790]. Conversely, A23:01 (P = 0.004), B07:02 (P = 0.003) and B42:01 (P = 0.025) are independently associated with rapid seroconversion. Women with any of these alleles are twice as likely to seroconvert (P = 0.002, OR: 2.059, 95% CI: 1.290-3.285). The beneficial alleles confer threefold protection from seroconversion when compared with the susceptible alleles (P = 0.000001, OR: 0.268, 95% CI: 0.132-0.544). B07:02 is the contributing allele, within the B7 supertype, to the rapid seroconversion. A74:01 (P = 0.04/P = 0.006), B14 (P = 0.003/P = 0.003) and B57:03 (P = 0.012/P = 0.038) are independently associated with slower CD4+ decline and LTNP phenotype, while B07:02 (P = 0.020), B15:10 (P = 0.022) and B53:01 (P = 0.007) are independently associated with rapid CD4+ T-cell decline. B7 supertype (P = 0.00006), B35*-Py (P = 0.028) and B*35-Px (P = 0.001) were also significantly associated with rapid CD4+ T-cell decline. Understanding why these HLA class I alleles are associated with protection/susceptibility to HIV-1 acquisition and disease progression could contribute to the development of effective prophylactic and therapeutic vaccines for HIV-1.

摘要

I类人类白细胞抗原（HLA）通过将抗原呈递给CD8 + T细胞，在适应性免疫反应中发挥重要作用。研究报告称，几种HLA I类等位基因与人类免疫缺陷病毒（HIV）感染个体的疾病进展差异相关，然而，与HIV - 1感染的抗性或易感性相关的I类关联报道较少。我们使用基于序列的分型方法，对超过1000名参与Pumwani性工作者队列研究的女性进行了HLA - A、-B和 - C分型。采用Kaplan - Meier分析来确定影响血清转化和疾病进展至获得性免疫缺陷综合征（CD4＜200/mm³）的等位基因。A01（P = 0.020）、C06:02（P = 0.042）和C07:01（P = 0.050）与预防血清转化独立相关。具有这些等位基因之一的女性血清转化的可能性较小[P = 0.00001，优势比（OR）：0.503，95%置信区间（CI）：0.320 - 0.790]。相反，A23:01（P = 0.004）、B07:02（P = 0.003）和B42:01（P = 0.025）与快速血清转化独立相关。具有这些等位基因之一的女性血清转化的可能性是其他人的两倍（P = 0.002，OR：2.059，95% CI：1.290 - 3.285）。与易感等位基因相比，有益等位基因对血清转化的保护作用高出三倍（P = 0.000001，OR：0.268，95% CI：0.132 - 0.544）。B07:02是B7超型中导致快速血清转化的等位基因。A74:01（P = 0.04/P = 0.006）、B14（P = 0.003/P = 0.003）和B57:03（P = 0.012/P = 0.038）与较慢的CD4 + 下降和长期不进展（LTNP）表型独立相关，而B07:02（P = 0.020）、B15:10（P = 0.022）和B53:01（P = 0.007）与快速的CD4 + T细胞下降独立相关。B7超型（P = 0.00006）、B35*-Py（P = 0.028）和B*35 - Px（P = 0.001）也与快速的CD4 + T细胞下降显著相关。了解这些HLA I类等位基因为何与HIV - 1感染的保护/易感性以及疾病进展相关，可能有助于开发有效的HIV - 1预防性和治疗性疫苗。