Dengue Group, National Institute of Virology, 20 A, Dr. Ambedkar Road, Pune 411001, Maharashtra, India.
Hum Immunol. 2013 Dec;74(12):1624-8. doi: 10.1016/j.humimm.2013.08.004. Epub 2013 Aug 20.
Human leukocyte antigen (HLA) class I alleles are known to affect the cytotoxic T lymphocyte responses and influence susceptibility to viral infections. The objective of the present study was to find out whether HLA class I alleles are associated with clinical manifestations of dengue virus infection. The profile of HLA class I alleles were investigated in 224 human subjects [85 dengue fever (DF) cases, 29 dengue hemorrhagic fever (DHF) cases and 110 healthy controls (HCs)] from Western India using PCR based methods. Results revealed significantly higher frequency of HLA-A(∗)33 in DF cases compared to HCs [P = 0.032, Odds ratio (OR) 2.12]. The frequency of HLA-A(∗)02:11 was higher in DHF cases compared to DF cases. The frequency of HLA-B(∗)18 was significantly higher in dengue (DEN) cases [P = 0.047 Pc = 0.846, OR 3.53]. The frequency of HLA-Cw(∗)07 allele was significantly higher in DEN cases [DEN vs. HCs: P = 0.0120, Pc = 0.168, OR 2.00]. Significance was observed even when the cases were categorized in to DF and DHF [DF vs. HCs: P = 0.0349, Pc = 0.49, OR 1.87; DHF vs. HCs: P = 0.0399, Pc = 0.56, OR 2.4]. The combined frequency of HLA-Cw(∗)07 with HLA-DRB1(∗)07/(∗)15 genotype was significantly higher in DHF cases as compared to DF and HCs [DHF vs. HCs: P = 0.022, OR 5.31; DHF vs. DF: P = 0.027, OR 5.49]. On the other hand, the frequency of combination of HLA-Cw(∗)07 without HLA-DRB1(∗)07 was significantly higher in DF cases compared to HCs [DF vs. HCs: P = 0.002, OR 2.42 (1.28-4.55)]. The results suggest that HLA-A(∗∗)33 may be associated with DF while HLA-B(∗)18 and HLA-Cw(∗)07 alleles may be associated with symptomatic dengue requiring hospitalization. In the presence of HLA-DRB1(∗)07/(∗)15 genotype, HLA-Cw(∗)07 is associated with increased risk of developing DHF while in the presence of other HLA-DRB1 alleles, HLA-Cw(∗)07 is associated with DF.
人类白细胞抗原(HLA)I 类等位基因已知会影响细胞毒性 T 淋巴细胞反应,并影响对病毒感染的易感性。本研究的目的是确定 HLA I 类等位基因是否与登革热病毒感染的临床表现有关。使用基于 PCR 的方法,在来自印度西部的 224 个人类受试者(85 例登革热(DF)病例、29 例登革出血热(DHF)病例和 110 例健康对照(HC))中研究了 HLA I 类等位基因的分布。结果显示,DF 病例中 HLA-A(∗)33 的频率明显高于 HC [P=0.032,优势比(OR)2.12]。与 DF 病例相比,DHF 病例中 HLA-A(∗)02:11 的频率更高。HLA-B(∗)18 在登革热(DEN)病例中的频率明显更高[P=0.047 Pc=0.846,OR 3.53]。HLA-Cw(∗)07 等位基因的频率在 DEN 病例中明显更高[DEN 与 HCs:P=0.0120,Pc=0.168,OR 2.00]。即使将病例分为 DF 和 DHF 进行分类,也观察到了统计学意义[DF 与 HCs:P=0.0349,Pc=0.49,OR 1.87;DHF 与 HCs:P=0.0399,Pc=0.56,OR 2.4]。与 DF 和 HCs 相比,DHF 病例中 HLA-Cw(∗)07 与 HLA-DRB1(∗)07/(∗)15 基因型的联合频率明显更高[DHF 与 HCs:P=0.022,OR 5.31;DHF 与 DF:P=0.027,OR 5.49]。另一方面,DF 病例中 HLA-Cw(∗)07 与 HLA-DRB1(∗)07 不结合的频率明显高于 HCs[DF 与 HCs:P=0.002,OR 2.42(1.28-4.55)]。结果表明,HLA-A(∗∗)33 可能与 DF 有关,而 HLA-B(∗)18 和 HLA-Cw(∗)07 等位基因可能与需要住院治疗的有症状登革热有关。在存在 HLA-DRB1(∗)07/(∗)15 基因型的情况下,HLA-Cw(∗)07 与发生 DHF 的风险增加有关,而在存在其他 HLA-DRB1 等位基因的情况下,HLA-Cw(∗)07 与 DF 有关。