HLA-Associated Hemorrhagic Fever with Renal Syndrome Disease Progression in Slovenian Patients
HLA-Associated Hemorrhagic Fever with Renal Syndrome Disease Progression in Slovenian Patients
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DOI：
10.1128/cvi.05187-11
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发表时间：
2011-09-01
影响因子：
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通讯作者：
Avsic-Zupanc, Tatjana
中科院分区：
文献类型：
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作者：
Korva, Misa;Saksida, Ana;Avsic-Zupanc, Tatjana
主要组织相容性复合体(MHC)I类和II类基因调节适当的侵袭性反应和入侵病原体之间的平衡，同时将对宿主组织的破坏降至最低。多项研究表明，在肾综合征出血热(HFRS)患者中，疾病结局由病毒与免疫病理和人类遗传因素之间的复杂相互作用决定。在斯洛文尼亚，由Puumala病毒(PUUV)引起的疾病严重程度明显低于由Dobrava病毒(DOBV)引起的HFRS。我们在斯洛文尼亚肾综合征出血热患者中检测了23种不同的人类白细胞抗原B和12种不同的人类白细胞抗原DRB1类型。汉坦病毒感染的易感性与正常人和肾综合征出血热患者之间的比较未见明显相关性。当根据感染的病毒将患者组分开时，发现了显著的相关性。DOBV感染患者的HLAB*35频率明显高于PUUV感染患者。对于HLAII类基因，PUUV感染组和DOBV感染组之间最大的差异是在HLADRB1*13，这种表型在PUUV感染的患者中更常见，特别是在疾病的严重形式中。在斯洛文尼亚人群中，人类白细胞抗原B*07可能对PUUV引起的肾综合征出血热起到保护作用。我们的研究表明，人类白细胞抗原分子与DOBV和PUUV诱导的肾综合征出血热有不同的相关性，因此，我们推测不同的汉坦病毒通过相同的人类白细胞抗原分子呈现不同的形式，这可能导致疾病的更严重或更轻微的形式。根据这一观点，我们注意到，在斯洛文尼亚人群中，人类白细胞抗原-B*35可能是DOBV感染的一个遗传危险因素。
Major histocompatibility complex (MHC) class I and class II genes regulate the balance between appropriate aggressive responses and invading pathogens while minimizing the destruction of host tissue. Several studies have shown that in hemorrhagic fever with renal syndrome (HFRS) patients, the disease outcome is determined by a complex interaction between the virus and immunopathologic and human genetic factors. In Slovenia, the severity of the disease caused by Puumala virus (PUUV) is significantly lower than that of HFRS due to Dobrava virus (DOBV). We have determined 23 different HLA-B and 12 different HLA-DRB1 types in Slovenian HFRS patients. Comparison of HLA frequencies between healthy individuals and HFRS patients showed no strong association with the susceptibility for hantaviral infection. Significant associations were recognized when the patient group was separated according to the virus responsible for the infection. DOBV-infected patients have a significantly higher frequency of HLA-B*35 than PUUV-infected patients. For HLA class II genes, the biggest difference between the PUUV- and DOBV-infected groups of patients was in HLA-DRB1*13, where this phenotype was more frequent in PUUV-infected patients, especially in the severe form of the disease. HLA-B*07 could play a protective role in PUUV-caused HFRS in the Slovenian population. Our study shows diverse associations of HLA molecules with DOBV- and PUUV-induced HFRS, and therefore, we presume that different hantaviruses are presented differently through the same HLA molecules and that this might lead to either a more severe or a milder form of the disease. In line with this idea, we have noticed that HLA-B*35 might be a genetic risk factor for DOBV infection in the Slovenian population.