THE PATHOGENETICAL ROLE OF VIRUS INFECTION AND ACTIVATION OF ONCOGENES.

为探讨病毒感染和原癌基因激活在胶原病发病过程中的作用，用免疫印迹法检测了66例SLE患者血清中EB病毒基因组阳性Raji和P3HR-1细胞及不同分化阶段髓系细胞的抗体。SLE患者血清中含有抗Raji细胞表型为66K、70K、90K、140K和160K的抗体，分别鉴定为c-myc蛋白和EB病毒核抗原(EBNA)亚型1、2、3和4型。抗EBNA-2和EBNA-3抗体的出现频率和抗体数量均显著高于60例正常对照血清。此外，从SLE患者的血清中还发现了针对K-562、KG-1和HL-60细胞上MR为60K的抗原的抗体，这些抗体也是已知的c-myc产物。用TPA或维生素D3诱导HL-60细胞向巨噬细胞分化后，SLE血清可检测到分化后的HL-60细胞上的55K和39K抗原，而60K抗原则检测不到或检测不到。应用抗myc特异性和fos特异性多肽的多克隆抗体与这些抗原反应，包括交叉实验。这些研究结果证实，SLE患者血清中含有针对c-myc、c-fos的抗体，并可能含有c-jun/AP-1原癌基因产物。此外，SLE患者外周血中EBNA阳性B细胞的频率是正常人B细胞的3倍。提示EB病毒感染后多个癌基因的激活可能在SLE的发病过程中起重要作用。

In order to clarify the role of virus infection and subsequent activation of protooncogenes on the triggering process of collagen disease,, the sera from 66 patients with SLE were analyzed by the immunoblotting method to detect antibodies to the antigens on the EB virus genome positive Raji and P3HR-1 cells, as well as on the cultured myeloid cell lines of various stages of differentiation. The sera from SLE patients were found to contain the antibodies to the antigens with Mr of 66K, 70K, 90K, 140K and 160K daltons on Raji cells which were identified as c-myc protein and EB virus nuclear antigen (EBNA) subtypes 1, 2, 3 and 4, respectively. The frequency and amount of antibodies against EBNA-2 and -3 were significantly higher than in 60 control normal sera. Further, the sera from SLE patient were found to have the antibodies to the antigens with Mr of 60K on K-562, KG-1 and HL-60 cells, which are also known to be c-myc product. After an incubation of HL-60 cells with TPA or vitamin D3 to induce their macrophage differentiation, the SLE sera became to detect the 55K and 39K antigens on the differentiated HL-60 cells, while the 60K antigen turned to undetectable or only faintly detected. Polyclonal antibodies to myc-specific and fos-specific peptides were applied to react with these antigens including cross experiments. The results of these studies confirmed that the sera from SLE patients contain antibodies to c-myc, c-fos and possibly c-Jun/AP-1 protooncogen products. In addition, SLE patients were found to show EBNA positive B cells at 3 times higher frequencies than that of B cells from normal subjects. It was suggested that EB virus infection with subsequent activation of several oncogenes may have an important pathogenetical role on the triggering process of SLE.