独特型多肽主动免疫对自发性自身免疫小鼠肾脏的保护作用

Immunization with a peptide derived from an Id^(LN) F1+ autoantibody delays the development of lupus nephritis in the murine model

目的 :既往的动物研究发现一组致病性的自身抗体IdLNF1 ,其表达与 (SWR×NZB)F1 (SNF1 )的狼疮性肾炎 (LN)发病有关。特异性T细胞参与了对这种抗体的识别和介导作用。来自于某一IdLNF1重链可变区的独特型多肽片段 62 73(aa62 73)也具有体外刺激这种特异性T细胞增生的作用。如果给予动物aa62 73免疫治疗 ,有可能改变SNF1的LN发病进程。 方法 :我们对尚未患LN的SNF1 ,MRL/ +,NZB/NZW小鼠进行aa62 73注射免疫。用来自于抗疟抗体重链可变区的多肽片段Mal作对照。并观察不同种系和不同年龄SNF1经治小鼠肾脏病理的改变。 结果 :治疗组小鼠 2 4周时肾脏病理损害明显低于对照组。于 1 4周起SNF1治疗组的肾脏损害也明显低于对照。 结论 :来自于自身抗体的独特型多肽片段对自发性自身免疫病小鼠的肾脏具有保护作用 。

Objective:ID LN F1,a pathogenic subset of antibodies was identified by previous work.And its expression has been shown to correlated with renal disease in the (SWRxNZB)F1(SNF1)murine model of lupus nephritis.T cell has acted a part identifying and transmitting ID LN F1.,A peptide corresponding to aa62 73 of the heavy chain of ID LN F1+autoantibody 540 was found contain a triple basic amino acid modified BX(X)BXB that has been found in numerous lupus antibodies,and was shown to stimulate syngeneic T cells from nephritic SNF1 mice.This suggested that autoreactive T cells which were stimulated by this idiotype,could be involved in the pathogenetic process in SNF1 nephritis.We hypothesized that immunization with this peptide should therefore modulate the process of the murine lupus nephritis. Methodology:The pre nephritic SNF1,(NZWxNZB)F1(W/B),and MRL/+ mouse was immunized with injecting aa62 73 in Freunds adjuvant beginning at 8 weeks of age.Controled mice received a peptide of the heavy chain derived from the anti malaria antibody.The renal histological lesions were analyzed in both groups of mice. Results:At the age of 24 weeks,the percentage of segmental and diffuse glomerular proliferation was significantly increased in controled mice,which was markedly improved by injecting with aa62 73.Furthermore,renal damage was significantly decreased in aa62 73 immunized SNF1 as early as 14 weeks. Conclusion:These suggested that a peptide derived from an ID LN F1+ autoantibody might have a renal protective effects for autoimmune mice model,and be possible to develop novel therapeutic strategies for SLE,especifically down regulated the pathogenic immune response.