马疫锥虫动基体DNA诱导抗dsDNA抗体产生条件与致病性的研究

Different immunization methods affect the production and pathogenicity of anti-dsDNA antibodies induced by kinetoplast DNA derived from trypanosoma equiperdum

目的研究不同免疫途径对马疫锥虫动基体DNA(kDNA)诱导正常小鼠产生抗双链DNA(dsDNA)抗体及其致病性的影响。方法将马疫锥虫kDNA与不完全弗氏佐剂乳化混合,通过皮下、腹腔、肌肉及静脉等途径注射入正常BALB/C小鼠。8周后,检测小鼠血清抗dsDNA抗体亚型及滴度、血尿素氮(BUN)、血肌酐(Scr)、补体C3、24h尿蛋白浓度、肾小球免疫复合物沉积强度、肾组织病变活动指数等,并分析肾组织病理学特征。结果上述各组小鼠产生IgG型抗dsDNA抗体量及肾损害程度依次为:皮下组>腹腔组>肌肉组>静脉组(P<0.05);IgG型抗dsDNA抗体与肾组织病变活动指数呈正相关。结论不同免疫途径对马疫锥虫kDNA诱导抗dsDNA抗体产生有明显不同影响,其导致的狼疮样肾脏损害与该抗体亚型有关。

Objective To study the effect of different immunization methods on the production and pathogenicity of anti-dsDNA antibodies induced by kinetoplast DNA （kDNA） derived from trypanosoma e quiperdum （TE） on normal mice. Methods The emulsive mixture of TE kDNA and incomplete Freund＇s adjuvant （IFA） was injected into normal BALB/c mice subcutaneously, intraperitoneally, intramuscularly or intravenously. These mice were immunized once every five days. Their sera titer of anti-dsDNA antibodies, BUN, Scr, C3, 24 h urine concentration, deposit intensity of renal immune-complex （IC） and renal histological active index （AI） were detected at the eighth week. The pathological characteristics of these mice＇s renal tissues were observed under ordinary optical and electron microscopes. Results The productive abilities of IgG suhtype of anti-dsDNA antibodies and renal damages of these four groups were in the following order： subcutaneous group〉 intraperitoneal group 〉 intramuscular group〉intravenous group. The lgG subtype of anti-dsDNA antibodies had positive but non-linear correlation with renal histological AI, while the IgM subtype had no significant relationship with it. Conclusion The anti-dsDNA antibodies can be induced by TE kDNA with different immunization methods. The IgG subtype of anti-dsDNA antibodies results in characteristic renal lesions that are similar to human lupus nephritis.