KIR2DL1 基因是喀麦隆未暴露于 HIV-1 的感染与未感染婴儿中与感染相关的住院保护的替代标志物。
KIR2DL1 gene is a surrogate marker of protection against infection-related hospitalization among HIV-1 unexposed versus exposed uninfected infants in Cameroon.
机构信息
Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Buéa, Buéa, Cameroon.
American Association of Microbiology (ASM), ASM Cameroon, Bangangté, Cameroon.
出版信息
BMC Immunol. 2024 Aug 1;25(1):54. doi: 10.1186/s12865-024-00645-9.
BACKGROUND
HIV-exposed uninfected infants (HEU) appear more vulnerable to infections compared to their HIV-unexposed uninfected (HUU) peers, generally attributed to poor passive immunity acquired from the mother. This may be due to some genetic factors that could alter the immune system. We thus sought to determine the distribution of Killer Cell Immunoglobulin-Like Receptors (KIRs) genes in HEU versus HUU and study their associations with the occurrence of infection-related hospitalization.
METHODS
A cohort study was conducted from May 2019 to April 2020 among HEU and HUU infants, including their follow-up at weeks 6, 12, 24, and 48, in reference pediatric centers in Yaoundé-Cameroon. The infant HIV status and infections were determined. A total of 15 KIR genes were investigated using the sequence-specific primer polymerase chain reaction (PCR-SSP) method. The KIR genes that were significantly associated with HIV-1 status (HEU and HUU) were analyzed for an association with infection-related hospitalizations. This was only possible if, and to the extent that, infection-related hospitalizations varied significantly according to status. Multivariate logistic regression analyses were conducted to determine the association between KIR gene content variants and HIV status, while considering a number of potential confounding factors. Furthermore, the risk was quantified using relative risk, odds ratio, and a 95% confidence interval. The Fisher exact test was employed to compare the frequency of occurrences. A p-value of less than 0.05 was considered statistically significant.
RESULTS
In this cohort, a total of 66 infants participated, but only 19 acquired infections requiring hospitalizations (14.81%, 04/27 HUU and 38.46%, 15/39 HEU, p = 0.037). At week 48 (39 HEU and 27 HUU), the relative risk (RR) for infection-related hospitalizations was 2.42 (95% CI: 1.028-5.823) for HEU versus HUU with OR 3.59 (1.037-12.448). KIR2DL1 gene was significantly underrepresented in HEU versus HUU (OR = 0.183, 95%CI: 0.053-0.629; p = 0.003), and the absence of KIR2DL1 was significantly associated with infection-related hospitalization (p < 0.001; aOR = 0.063; 95%CI: 0.017-0.229).
CONCLUSION
Compared to HUU, the vulnerability of HEU is driven by KIR2DL1, indicating the protective role of this KIR against infection and hospitalizations.
背景
与未感染 HIV 的婴儿（HUU）相比，HIV 暴露未感染婴儿（HEU）似乎更容易感染，这通常归因于从母亲那里获得的较差的被动免疫。这可能是由于一些可能改变免疫系统的遗传因素。因此，我们试图确定 HEU 与 HUU 之间杀伤细胞免疫球蛋白样受体（KIR）基因的分布，并研究它们与感染相关住院的关系。
方法
2019 年 5 月至 2020 年 4 月，在喀麦隆雅温得的儿科中心，对 HEU 和 HUU 婴儿进行了队列研究，包括他们在第 6、12、24 和 48 周的随访。通过聚合酶链反应（PCR-SSP）方法用序列特异性引物检测婴儿的 HIV 状态和感染情况。用序列特异性引物聚合酶链反应（PCR-SSP）方法检测了 15 种 KIR 基因。对与 HIV-1 状态（HEU 和 HUU）显著相关的 KIR 基因进行了分析，以研究其与感染相关住院的关系。只有在感染相关住院的情况根据状态有显著差异的情况下，才有可能进行分析。采用多变量逻辑回归分析，在考虑了一些潜在的混杂因素的情况下，确定 KIR 基因含量变异与 HIV 状态之间的关系。此外，还使用相对风险、优势比和 95%置信区间来量化风险。Fisher 精确检验用于比较发生频率。p 值小于 0.05 被认为具有统计学意义。
结果
在该队列中，共有 66 名婴儿参与，但只有 19 名婴儿发生了需要住院的感染（14.81%，04/27 HUU 和 38.46%，15/39 HEU，p=0.037）。在第 48 周（39 名 HEU 和 27 名 HUU），HEU 与 HUU 相比，感染相关住院的相对风险（RR）为 2.42（95%CI：1.028-5.823），OR 为 3.59（1.037-12.448）。与 HUU 相比，HEU 中 KIR2DL1 基因明显减少（OR=0.183，95%CI：0.053-0.629；p=0.003），KIR2DL1 缺失与感染相关住院显著相关（p<0.001；aOR=0.063；95%CI：0.017-0.229）。
结论
与 HUU 相比，HEU 的脆弱性是由 KIR2DL1 驱动的，这表明这种 KIR 对感染和住院具有保护作用。
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