Hannig H, Buske C, Mätz-Rensing K, Hunsmann G, Hiddemann W, Bodemer W
German Primate Center, Department for Virology and Immunology, Göttingen.
Int J Cancer. 1998 Aug 31;77(5):734-40. doi: 10.1002/(sici)1097-0215(19980831)77:5<734::aid-ijc12>3.0.co;2-1.
Patients with HIV infection are at high risk for the development of high-grade B-non-Hodgkin's lymphoma (B-NHL). The aim of this study was identification of a predictive diagnostic marker for HIV-associated B-cell lymphomas, using simian-immunodeficiency-virus (SIV)-infected Rhesus monkeys as a well-established in vivo model of HIV-associated lymphomagenesis. We infected 26 monkeys (Macaca mulatta) with SIVmax and measured serum levels of sCD23 longitudinally until necropsy. Of the 26 monkeys, 9 developed high-grade B-NHL, which was preceded by lymphadenopathy (NHL+/LA+) (group 1). Among the 17 animals that remained without clinical evidence of lymphoma during the observation period, 8 developed LA (group 2) and 9 were NHL- and LA-negative (NHL-/LA-) (group 3). Elevation of sCD23 serum levels preceded B-cell lymphoma development, with a median of 44 U/ml in group 1 vs. 7 U/ml and 8 U/ml in groups 2 and 3 respectively, 32 weeks after infection. Differences in the serum level of sCD23 between group 1 vs. groups 2 and 3 became statistically significant 32 to 56 weeks after infection. At necropsy, serum levels of sCD23 were significantly higher in group 1 than in group 2 or group 3; 6/6 samples of SIV-associated B-NHL were positive for gene transcription of CD23 and its receptor CD21 as assessed by RT-PCR. The data point to a potential role of sCD23 as a predictive marker for the development of HIV-associated B-NHL. Moreover, the in vivo model of SIV-infected monkeys suggests the possibility of exactly analyzing the pathobiological role of sCD23 in the lymphomagenesis of SIV-associated B-NHL.
感染HIV的患者发生高级别B细胞非霍奇金淋巴瘤(B-NHL)的风险很高。本研究的目的是利用感染猿猴免疫缺陷病毒(SIV)的恒河猴作为HIV相关淋巴瘤发生的成熟体内模型,确定一种用于HIV相关B细胞淋巴瘤的预测性诊断标志物。我们用SIVmax感染了26只猴子(食蟹猴),并纵向测量血清sCD23水平直至尸检。在这26只猴子中,9只发生了高级别B-NHL,在发生淋巴瘤之前有淋巴结病(NHL+/LA+)(第1组)。在观察期内没有淋巴瘤临床证据的17只动物中,8只发生了淋巴结病(第2组),9只既没有淋巴瘤也没有淋巴结病(NHL-/LA-)(第3组)。sCD23血清水平升高先于B细胞淋巴瘤的发生,感染后32周,第1组的中位数为44 U/ml,第2组和第3组分别为7 U/ml和8 U/ml。第1组与第2组和第3组之间sCD23血清水平的差异在感染后32至56周具有统计学意义。尸检时,第1组的sCD23血清水平显著高于第2组或第3组;通过逆转录聚合酶链反应(RT-PCR)评估,6/6例SIV相关B-NHL样本的CD23及其受体CD21基因转录呈阳性。数据表明sCD23可能作为HIV相关B-NHL发生的预测标志物。此外,SIV感染猴子的体内模型提示了准确分析sCD23在SIV相关B-NHL淋巴瘤发生中的病理生物学作用的可能性。