Immune Activation: Contribution to AIDS-Associated Non-Hodgkin Lymphoma.
Immune Activation: Contribution to AIDS-Associated Non-Hodgkin Lymphoma.
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DOI：
10.1615/forumimmundisther.2016014177
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Martinez-Maza, Otoniel
中科院分区：
文献类型：
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作者：
Epeldegui, Marta;Martinez-Maza, Otoniel
HIV 感染与患非霍奇金淋巴瘤 (NHL) 的风险大大升高相关，尽管这种风险有所降低，但在高度活跃的抗逆转录病毒治疗 (HAART) 时代，这种风险仍然很高。在 HIV 感染者中，由于与 HIV 病毒体、B 细胞刺激性细胞因子、病毒（EBV、HPV、HCV）的接触以及高水平的抗原刺激，导致 B 细胞慢性激活，并且在那些继续发展为 AIDS-NHL 的人中，这种激活水平甚至更高。多项研究的证据表明，在艾滋病-非霍奇金淋巴瘤之前以及在发展为非霍奇金淋巴瘤的免疫功能正常的人中，几种 B 细胞刺激性细胞因子和生物标志物的血清水平升高。循环 B 细胞的表型变化也出现在 AIDS-NHL 之前，包括 AICDA 以及与激活的 B 细胞相关的细胞表面分子和 miRNA 的表达。 HAART 仅使接受治疗的 HIV+ 患者的免疫系统部分正常化，因为他们仍然显示出持续炎症和免疫激活的明确证据，甚至是那些完全抑制 HIV 病毒血症的患者。总之，这提供了充足的证据来支持 B 细胞的慢性激活导致 B 细胞淋巴瘤发生的观点。
HIV infection is associated with a greatly elevated risk for the development of non-Hodgkin lymphoma (NHL), which while diminished, remains elevated in the highly active antiretroviral therapy (HAART) era. Chronic B cell activation, driven by contact with HIV virions, B cell-stimulatory cytokines, viruses (EBV, HPV, HCV), and by high levels of antigenic stimulation occurs in HIV infected persons, and it is seen at even higher levels in those who go on to develop AIDS-NHL. Evidence from multiple studies indicates that elevated serum levels of several B cell-stimulatory cytokines and biomarkers are seen preceding AIDS-NHL, as well as in immunocompetent persons that develop NHL. Phenotypic changes in circulating B cells also are seen preceding AIDS-NHL, including the expression of AICDA, and of cell-surface molecules and miRNA that are associated with activated B cells. HAART only partially normalizes the immune system of treated HIV+ persons as they still show clear evidence for ongoing inflammation and immune activation in, even those who show complete suppression of HIV viremia. Together, this provides ample evidence to support the notion that chronic activation of B cells contributes to the genesis of B cell lymphomas.