人类白细胞抗原-B特异性抗原表位Bw4对丙型肝炎病毒感染的影响

Impact of human leukocyte antigen-B specific Bw4 epitope on hepatitis C virus infection

目的探讨人类白细胞抗原（HLA）-B分子特异性抗原表位Bw4对HCV感染病情进展的影响。方法有偿献血途径感染HCV的患者86例纳入研究，ELISA法检测患者血清HCVIgG和HCVIgM，实时RT—PCR检测患者血HCVRNA，序列特异性PCR扩增技术（SSP—PCR）进行HIA分型。计数资料比较采用行×列χ^2检验，两组计量资料比较采用独立样本t检验。结果86例HCV感染者中，BW4／4纯合子29例，占33．7％；BW4／6杂合子38例，占44．2％；BW6／6纯合子19例，占22．1％。Bw4／4纯合子、Bw4／6杂合子、BW6／6纯合子患者HCV RNA水平分别为（3．98±0．32）、（5．22±0．29）和（5．04±0．38）lg IU／mL，Bw4／4纯合子患者HCV RNA明显低于Bw4／6杂合子、Bw6／6纯合子组（t=2．821，P=0．0063；t=2．106，P=0．0407）。Bw4／4纯合子、Bw4／6杂合子、BW6／6纯合子HCV感染者中，自然清除率分别为58．6％、26．3％及21．0％，Bw4／4纯合子者HCV自发清除率明显高于Bw4／6杂合子、BW6／6纯合子患者（χ^2=7．135，P=0．008；χ^2=6．583，P=0．010）。携带Bw4／4纯合子抗原表位的HCV感染者发生病毒自发清除的可能性是Bw4／6杂合子及BW6／6纯合子的4．351倍（OR=4．351，95％CI：1．676～11．294）。结论携带Bw4／4纯合子的HCV感染者，病毒载量较低、病毒自发清除率较高，Bw4抗原表位对HCV感染具有一定的保护性。

Objective To study the impact of human leukocyte antigen （HLA）-B specific Bw4 epitope on disease progression of hepatitis C virus （HCV） infection. Methods Eighty-six cases of HCV infection through paid blood donation were enrolled in the study. Enzyme-linked immunosorbent assay （ELISA） to detect HCV IgG and IgM, real-time reverse transcriptation polymerase chain reaction （RT-PCR） to detect HCV RNA, and sequence specific primer-polymerase chain reaction （SSP-PCR） to analyze HLA type was performed. Categorical data were analyzed by chi-square test, and measurement data were compared by independent sample t test. Results Among the 86 HCV infected individuals, there were 29 （33.7%） cases of Bw4/4 homozygote, 38 cases （44.2%） of Bw4/ 6 heterozygote and 19 （22.1%） cases of Bw6/6 homozygote. The HCV RNA levels in Bw4/4 group,Bw4/6 group and Bw6/6 group were （3. 98±0. 32）, （5. 22±0. 29）, （5. 04±0. 38） lg IU/mL, respectively. The HCV RNA level in Bw4/4 group was significantly lower than those in the other two groups （t=2. 821 ,P=0. 0063;t=2. 106,P=0. 0407, respectively）. The spontaneous clearance rates of Bw4/4 group, Bw4/6 group and BW6/6 group were 58. 6%, 26. 3% and 21.0%, respectively. The spontaneous clearance rate of Bw4/4 group was significantly higher than those of Bw4/6 group andBw6/6 group （χ^2 =7. 135,P=0. 008;χ^2=6. 583, P=0. 010, respectively）. HCV infected individuals with homozygous epitopes of Bw4/4 had 4. 351 times higher probability of spontaneous viral clearance than that of Bw4/6 heterozygote or Bw6/6 homozygote （OR = 4. 351,95% CI： 1. 676- 11. 294）. Conclusions Homozygosity for HLA Bw4-bearing B alleles is associated with significant lower HCV viral load and higher spontaneous clearance rate. The HLA-Bw4 epitopes have a protective effect against HCV infection.