Hospital General Dr. Manuel Gea González, México, DF 14080, Mexico.
J Clin Virol. 2013 Sep;58(1):108-13. doi: 10.1016/j.jcv.2013.05.013. Epub 2013 Jun 26.
In Mexico, the initial severe cases of the 2009 influenza pandemic virus A (H1N1) [A(H1N1)pdm09] were detected in early March. The immune mechanisms associated with the severe pneumonia caused by infection with this new virus have not been completely elucidated. Polymorphisms in interleukin genes have previously been associated with susceptibility to infectious diseases due to their influence on cytokine production.
The present case-control study was performed to compare several immunologic and genetic parameters of patients and controls during the initial phase of the pandemic.
Sixty-five patients who were hospitalized due to infection with the influenza A(H1N1)pdm09 virus and 46 healthy controls were studied. A hemagglutination inhibition assay (HIA) was performed to measure anti-influenza antibody titers in these subjects. Protein levels of the cytokines interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), interferon gamma (IFNγ), transforming growth factor beta (TGFβ)1 and TGFβ2 were quantified in plasma. Single nucleotide polymorphisms in IL6, IL10 and TNFα were also assessed.
Influenza patients had lower antibody titers and produced significantly higher levels of IL-6, IL-10 and TNFα than healthy controls. The frequencies of the TNFα -308G, IL-10 -592C and IL-10 -1082A alleles and the IL10 -1082(A/A) genotype were associated with susceptibility to severe disease, while the haplotypes TNFα AG and IL-10 GTA and GCA were associated with protection from severe disease [P=0.016, OR (CI)=0.11 (0.01-0.96); P=0.0187, OR (CI)=0.34 (0.13-0.85); P=0.013, OR (CI)=0.39 (0.18-0.83)].
This study demonstrates that the influenza A(H1N1)pdm09 patients and healthy controls have different profiles of immune parameters and that there is an association between IL-10 and TNFα polymorphisms and the outcome of this disease.
2009 年甲型流感病毒 A（H1N1）[A（H1N1）pdm09]在墨西哥的首例重症病例于 3 月初被发现。感染这种新型病毒引起的严重肺炎的免疫机制尚未完全阐明。白细胞介素基因的多态性与细胞因子的产生有关，先前与易感性传染病有关。
本病例对照研究旨在比较大流行初期患者和对照者的几种免疫和遗传参数。
对 65 例因感染甲型流感病毒 A（H1N1）pdm09 而住院的患者和 46 例健康对照者进行了研究。对这些受试者进行血凝抑制试验（HIA）以测量抗流感抗体滴度。在血浆中定量检测细胞因子白细胞介素（IL）-4、IL-6、IL-8、IL-10、肿瘤坏死因子-α（TNFα）、干扰素γ（IFNγ）、转化生长因子β（TGFβ）1 和 TGFβ2 的蛋白水平。还评估了 IL6、IL10 和 TNFα 中的单核苷酸多态性。
流感患者的抗体滴度较低，且比健康对照者产生更高水平的 IL-6、IL-10 和 TNFα。TNFα-308G、IL-10-592C 和 IL-10-1082A 等位基因的频率和 IL10-1082（A/A）基因型与严重疾病易感性相关，而 TNFα AG 和 IL-10 GTA 和 GCA 单倍型与严重疾病的保护相关[P=0.016，OR（CI）=0.11（0.01-0.96）；P=0.0187，OR（CI）=0.34（0.13-0.85）；P=0.013，OR（CI）=0.39（0.18-0.83）]。
本研究表明，甲型流感病毒 A（H1N1）pdm09 患者和健康对照者具有不同的免疫参数谱，IL-10 和 TNFα 多态性与疾病的结果之间存在关联。
