Besson Caroline, Raphaël Martine
Unité 550 Génétique humaine des maladies infectieuses, Faculté Necker, 156, rue de Vaugirard, 75015 Paris.
Ann Med Interne (Paris). 2003 Dec;154(8):523-8.
The incidence of lymphomas is high among HIV infected patients. These lymphomas are non-Hodgkin's lymphoma (NHL) in 70% of cases and Hodgkin's disease (HD) in 30% of cases. Their localization is often extra-nodal with early dissemination. B-cell high grade NHL predominates. The most frequent histological types are diffuse large B-cell lymphoma (30 to 40%) and Burkitt's lymphoma (40 to 50%). Other histological types are low-grade B-cell lymphoma, polymorphic B cell lymphoma and primary effusion lymphoma. Three main factors are predominant in HIV-related lymphomagenesis: cellular immunodeficiency, oncogene viruses (Epstein-Barr and HHV8) and molecular lesions. HIV-related cellular immunodeficiency leads to the increase of EBV infected B-cells and to the diminution of antitumor immunity. Clonal EBV genome is found in lymphoma cells in 30 to 70% of cases of HIV-related NHL. It expresses oncogenic proteins including LMP-1 which behaves like an activated CD40. It induces the expression of intra-cellular genes which stimulate cell growth and inhibit apoptosis. Cytogenetic and molecular lesions are not specific to HIV-related NHL or to histological subtypes. A better knowledge of these mechanisms should lead to the development of specific targeted treatments (antiviral, cytotoxic anti-EBV lymphocytes, cell cycle regulators).
淋巴瘤在HIV感染患者中的发病率很高。这些淋巴瘤70%为非霍奇金淋巴瘤（NHL），30%为霍奇金病（HD）。其定位通常在结外，且早期就会扩散。B细胞高级别NHL占主导。最常见的组织学类型是弥漫性大B细胞淋巴瘤（30%至40%）和伯基特淋巴瘤（40%至50%）。其他组织学类型包括低级别B细胞淋巴瘤、多形性B细胞淋巴瘤和原发性渗出性淋巴瘤。在与HIV相关的淋巴瘤发生过程中，三个主要因素起主导作用：细胞免疫缺陷、致癌病毒（爱泼斯坦-巴尔病毒和HHV8）和分子病变。与HIV相关的细胞免疫缺陷导致EBV感染的B细胞增加，抗肿瘤免疫力降低。在30%至70%的与HIV相关的NHL病例的淋巴瘤细胞中发现克隆性EBV基因组。它表达致癌蛋白，包括表现得像活化CD40的LMP-1。它诱导刺激细胞生长和抑制细胞凋亡的细胞内基因的表达。细胞遗传学和分子病变并非与HIV相关的NHL或组织学亚型所特有。对这些机制的更好了解应能促成特异性靶向治疗（抗病毒、细胞毒性抗EBV淋巴细胞、细胞周期调节剂）的开发。
