Reexamining the role of the humoral immune response in control of hepatitis C virus infection.
Reexamining the role of the humoral immune response in control of hepatitis C virus infection.
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重新审视体液免疫反应在控制丙型肝炎病毒感染中的作用。
DOI：
10.1002/hep.20376
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Dustin,LynnB
中科院分区：
文献类型：
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作者：
Dustin,LynnB
免疫球蛋白GM和KM同种异型--分别是γ和κ链的遗传标记--与对几种感染性病原体的免疫应答和在某些病毒流行中的存活相关。我们假设GM和KM同种异型影响丙型肝炎病毒（HCV）感染的结果。为了验证这一假设，我们对100名有明确记录的HCV感染清除者和198名匹配的持续感染者进行了血清学同种异型分型。GM或KM表型本身与HCV感染的清除或持续无关。然而，这些表型的特定组合与HCV感染的结果显著相关。具有GM 1，17 5，1,3和KM 1，3表型的受试者清除感染的可能性是缺乏这些表型的受试者的3倍以上（比值比[OR]，3.57; 95%置信区间[CI]，1.44-8.87）。在不存在KM 3的情况下，这种GM表型与清除率具有类似的相关性（OR，2.75; 95%CI，1.21-6.23）。GM 1，3，17 23 5，1,3表型的存在（不存在KM 3）与持续性相关（OR，0.21; 95%CI，0.06-0.77），而GM 1，3，1,3表型的缺失（存在KM 1，3）与感染清除相关（OR，2.03; 95%CI，1.16-3.54）。这些结果显示了染色体14（GM）和2（KM）上的基因在影响HCV感染的结果中的上位相互作用。需要进一步研究候选基因（GM、KM、HLA和Fcγ受体）以及对HCV表位的细胞和体液免疫应答，以了解这些相关性的机制。
Immunoglobulin GM and KM allotypes—genetic markers of γ and κ chains, respectively—are associated with immune responsiveness to several infectious pathogens and with survival in certain viral epidemics. We hypothesized that GM and KM allotypes affect the outcome of hepatitis C virus (HCV) infection. To test this hypothesis, we serologically allotyped 100 persons with well‐documented clearance of HCV infection and 198 matched persistently infected persons. None of the GM or KM phenotypes by itself was associated with the clearance or persistence of HCV infection. Particular combinations of these phenotypes, however, were significantly associated with the outcome of HCV infection. Subjects with GM 1,17 5,13 and KM 1,3 phenotypes were over three times (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.44–8.87) as likely to clear the infection as the subjects who lacked these phenotypes. This GM phenotype had a similar association with clearance in the absence of KM 3 (OR, 2.75; 95% CI, 1.21–6.23). The presence of GM 1,3,17 23 5,13 phenotype (in the absence of KM 3) was associated with persistence (OR, 0.21; 95% CI, 0.06–0.77), while its absence (in the presence of KM 1,3) was associated with the clearance of infection (OR, 2.03; 95% CI, 1.16–3.54). These results show epistatic interactions of genes on chromosomes 14 (GM) and 2 (KM) in influencing the outcome of an HCV infection. Further investigations involving candidate genes (GM, KM, HLA, and Fcγ receptors) and cellular and humoral immune responses to HCV epitopes are needed to understand the mechanisms underlying these associations.