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持续性感染及其与选定的肿瘤和非肿瘤病理学的关系。

Persistent infections and their relationship with selected oncologic and non-tumor pathologies.

机构信息

S.I. Research Centre for Radiation Medicine, Kyiv, Ukraine.

出版信息

J Immunotoxicol. 2010 Oct-Dec;7(4):279-88. doi: 10.3109/1547691X.2010.489528. Epub 2010 Jun 3.

Abstract

Our earlier studies of hepatitis C virus (HCV) infection rates among blood donors at the Kyiv Municipal Blood Center revealed a 3.45% HCV+ prevalence in these "healthy" hosts. In the study here, we analyzed HCV (as well as cytomegalovirus [CMV]) prevalence among Chernobyl nuclear power plant (NPP) accident sufferers--cleanup workers, local residents, NPP workers, and convalescent patients--who suffered acute radiation syndrome (ARS) as a result of the 1986 accident, and individuals who had not been exposed to ionizing radiation (IR). Serological analyses of antibodies against each pathogen (via enzyme-linked immunosorbent assay [ELISA]) revealed the highest HCV (i.e., 27.2%) and CMV (85.6%) prevalence in the convalescent hosts. Though the HCV prevalence (reflecting a current/past infection) among the cleanup workers (and other groups) was lower (i.e., 11-25%), viral presence was "associated" with a higher incidence of selected somatic diseases, for example, thyroiditis, goiter, hypertension, Type 1 diabetes, chronic hepatitis/gastritis, in the cleanup workers. A similar scenario with respect to CMV was also seen, i.e., lower prevalence rates [relative to in ARS patients] and "association" between CMV status and incidence of chronic gastritis, arthritis, and bronchitis, in the cleanup workers and IR-non-exposed controls. Further, irrespective of CMV status, there was a clear delineation between incidence rate(s) of each of the pathologies and whether or not the person was/was not exposed in 1986. We also investigated, due to a high incidence of chronic lymphocytic leukemia (CLL) among Chernobyl sufferers, if there was homology between immunoglobulins (Igs) generated by these transformed cells and known antiviral and antimicrobial Igs. Polymerase chain reaction (PCR) analyses of Ig heavy-chain variable (IgHV) genes in cells from CLL patients who were/were not exposed in 1986 revealed a significant homology of some IgHV genes with Igs directed against infectious agents. However, no differences were found between the sequences from IR-exposed and IR-non-exposed CLL patients. Based on the findings here, we conclude that a past/ongoing presence of certain viral infections (i.e., CMV and/or HCV) in a host can modify (aggravate) the clinical course of certain somatic (i.e., non-tumor) diseases and promote malignancies (i.e., CLL), and that each of these outcomes could be modulated as a result of that host's past exposure to IR.

摘要

我们之前对基辅市血液中心献血者的丙型肝炎病毒 (HCV) 感染率进行了研究,发现这些“健康”宿主的 HCV+患病率为 3.45%。在本研究中,我们分析了切尔诺贝利核电站 (NPP) 事故受害者——清理人员、当地居民、NPP 工作人员和康复患者——的 HCV(以及巨细胞病毒 [CMV])患病率,他们因 1986 年的事故而患有急性辐射综合征 (ARS),以及未接触电离辐射 (IR) 的个体。通过酶联免疫吸附试验 (ELISA) 对每种病原体的抗体进行血清学分析,结果发现康复宿主的 HCV(即 27.2%)和 CMV(85.6%)患病率最高。虽然清理工人(和其他群体)的 HCV 患病率(反映了当前/过去的感染)较低(即 11-25%),但病毒的存在与某些选定的躯体疾病的发病率较高相关,例如甲状腺炎、甲状腺肿、高血压、1 型糖尿病、慢性肝炎/胃炎,在清理工人中。对于 CMV 也存在类似的情况,即相对于 ARS 患者,[相对]较低的患病率以及 CMV 状态与慢性胃炎、关节炎和支气管炎的发病率之间的“关联”,在清理工人和非暴露于 IR 的对照组中。此外,无论 CMV 状态如何,每种疾病的发病率之间都有明显的区别,无论这个人是否在 1986 年受到过暴露。由于切尔诺贝利患者慢性淋巴细胞白血病 (CLL) 的发病率较高,我们还进行了研究,以确定这些转化细胞产生的免疫球蛋白 (Igs)与已知的抗病毒和抗微生物 Ig 是否具有同源性。对 1986 年未暴露和暴露于 CLL 患者的细胞中的 Ig 重链可变 (IgHV) 基因进行聚合酶链反应 (PCR) 分析,发现一些 IgHV 基因与针对感染因子的 Ig 具有显著同源性。然而,在暴露于 IR 和未暴露于 IR 的 CLL 患者的序列之间未发现差异。基于这里的发现,我们得出结论,宿主中某些病毒感染(即 CMV 和/或 HCV)的过去/持续存在会改变(加重)某些躯体(即非肿瘤)疾病的临床过程并促进恶性肿瘤(即 CLL)的发生,并且这些结果中的每一个都可以通过宿主过去暴露于 IR 来调节。

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