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人类对多房棘球绦虫感染的抗性/易感性及细胞因子谱。II. HLA B8、DR3、DQ2单倍型的影响。

Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. II. Influence of the HLA B8, DR3, DQ2 haplotype.

作者信息

Godot V, Harraga S, Beurton I, Tiberghien P, Sarciron E, Gottstein B, Vuitton D A

机构信息

WHO Collaborating Centre on Prevention and Treatment of Human Echinococcosis, Faculté de Médecine et de Pharmacie, Besançon Cedex, France.

出版信息

Clin Exp Immunol. 2000 Sep;121(3):491-8. doi: 10.1046/j.1365-2249.2000.01309.x.

Abstract

Differences have been shown between HLA characteristics of patients with different courses of alveolar echinococcosis (AE). Notably the HLA B8, DR3, DQ2 haplotype was associated with more severe forms of this granulomatous parasitic disease. We compared IL-10, IL-5, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) secretion by peripheral blood mononuclear cells (PBMC) isolated from eight HLA-DR3+, DQ2+, B8+ AE patients and from 10 HLA-DR3-, DQ2-, B8- patients after non-specific mitogenic and specific Echinococcus multilocularis antigenic in vitro stimulation. PBMC from seven HLA-DR3+, DQ2+, B8+ healthy subjects and nine HLA-DR3-, DQ2-, B8- subjects were also studied as controls. PBMC from AE patients with HLA DR3+, DQ2+ haplotype secreted higher levels of IL-10 without any stimulation and after specific antigenic stimulation than did patients without this haplotype. Higher levels of IL-5 and IFN-gamma were also produced by these patients' PBMC after stimulation with non-purified parasitic antigenic preparations; however, the specific alkaline phosphatase antigen extracted from E. multilocularis induced only Th2-type cytokine secretion. A spontaneous secretion of TNF by HLA DR3+, DQ2+ B8+ AE patients was also found. These results suggest that HLA characteristics of the host can influence immune-mediated mechanisms, and thus the course of AE in humans; specific antigenic components of E. multilocularis could contribute to the preferential Th2-type cytokine production favoured by the genetic background of the host.

摘要

不同病程的肺泡型棘球蚴病(AE)患者的人类白细胞抗原(HLA)特征存在差异。值得注意的是,HLA B8、DR3、DQ2单倍型与这种肉芽肿性寄生虫病的更严重形式相关。我们比较了从8名HLA - DR3 +、DQ2 +、B8 +的AE患者和10名HLA - DR3 -、DQ2 -、B8 -的患者中分离出的外周血单个核细胞(PBMC)在非特异性丝裂原和特异性多房棘球绦虫抗原体外刺激后白细胞介素-10(IL - 10)、白细胞介素-5(IL - 5)、干扰素-γ(IFN - γ)和肿瘤坏死因子(TNF)的分泌情况。还研究了7名HLA - DR3 +、DQ2 +、B8 +的健康受试者和9名HLA - DR3 -、DQ2 -、B8 -的受试者的PBMC作为对照。具有HLA DR3 +、DQ2 +单倍型的AE患者的PBMC在无任何刺激时以及特异性抗原刺激后分泌的IL - 10水平高于无此单倍型的患者。这些患者的PBMC在用未纯化的寄生虫抗原制剂刺激后也产生了更高水平的IL - 5和IFN - γ;然而,从多房棘球绦虫中提取的特异性碱性磷酸酶抗原仅诱导Th2型细胞因子分泌。还发现HLA DR3 +、DQ2 +、B8 +的AE患者存在TNF的自发分泌。这些结果表明,宿主的HLA特征可影响免疫介导机制,从而影响人类AE的病程;多房棘球绦虫的特异性抗原成分可能有助于宿主遗传背景所青睐的Th2型细胞因子的优先产生。

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