Department of Pathology, University of Arizona, Tucson, Arizona.
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
AIDS. 2020 Nov 15;34(14):2025-2035. doi: 10.1097/QAD.0000000000002653.
The increased risk for persons living with HIV to develop diffuse large B-cell lymphoma (DLBCL) even in the post-antiretroviral therapy eras suggests a role beyond immunosuppression in lymphoma development. However, the mechanisms leading to lymphoma in the HIV setting are not fully understood. HIV is known to induce activation-induced cytidine deaminase (AID) levels in nonneoplastic B cells in vitro and chronic AID expression may play an important role in lymphomagenesis. Although AID expression is observed in B-cell lymphoma, studies in HIV-associated DLBCL are limited.
In this study, we conducted a retrospective review of DLBCL tissues from patients with and without HIV infection to compare expression of AID and B-cell receptors potentially involved in HIV and B-cell interaction.
We evaluated DLBCL formalin-fixed paraffin-embedded tissues from 72 HIV-seropositive and 58 HIV-seronegative patients for AID, DC-SIGN, and CD40 protein expression. BCL2 and MYC, two well established prognostically significant oncoproteins in DLBCL, were also assessed at the protein and mRNA levels. Subset analysis was performed according to DLBCL subtype and EBV status.
Of note, AID expression was more frequent in HIV-associated DLBCL compared with non-HIV-associated DLBCL regardless of cell-of-origin subtype, and also displayed significantly less BCL2 expression. Despite no direct correlation with AID expression, the HIV-DLBCL tissues also exhibited high levels of the DC-SIGN receptor.
Collectively, these findings support a potential role for AID in the pathogenesis of HIV-associated lymphomas and suggest the need of further investigations into the involvement of the DC-SIGN receptor-signaling pathway.
即使在抗逆转录病毒治疗时代之后，艾滋病毒感染者发生弥漫性大 B 细胞淋巴瘤（DLBCL）的风险增加，这表明在淋巴瘤发展中存在免疫抑制以外的作用。然而，导致 HIV 环境中发生淋巴瘤的机制尚未完全阐明。已知 HIV 在体外可诱导非肿瘤性 B 细胞中的激活诱导胞苷脱氨酶（AID）水平，慢性 AID 表达可能在淋巴瘤发生中发挥重要作用。尽管在 B 细胞淋巴瘤中观察到 AID 表达，但在 HIV 相关 DLBCL 中的研究有限。
在这项研究中，我们对来自 HIV 感染和未感染患者的 DLBCL 组织进行了回顾性分析，以比较潜在参与 HIV 和 B 细胞相互作用的 AID 和 B 细胞受体的表达。
我们评估了 72 例 HIV 血清阳性和 58 例 HIV 血清阴性患者的 DLBCL 福尔马林固定石蜡包埋组织中的 AID、DC-SIGN 和 CD40 蛋白表达。还在蛋白和 mRNA 水平上评估了 DLBCL 中两个已确立的预后意义重大的癌蛋白 BCL2 和 MYC。根据 DLBCL 亚型和 EBV 状态进行了亚组分析。
值得注意的是，与非 HIV 相关的 DLBCL 相比，AID 在 HIV 相关的 DLBCL 中表达更为频繁，而与细胞起源亚型无关，并且也显示出明显较少的 BCL2 表达。尽管与 AID 表达没有直接相关性，但 HIV-DLBCL 组织也表现出高水平的 DC-SIGN 受体。
总的来说，这些发现支持 AID 在 HIV 相关淋巴瘤发病机制中的潜在作用，并表明需要进一步研究 DC-SIGN 受体信号通路的参与。
