Mason L J, Timothy L M, Isenberg D A, Kalsi J K
Center for Rheumatology/Bloomsbury Rheumatology Unit, Department of Medicine, University College London, United Kingdom.
J Immunol. 1999 May 1;162(9):5099-105.
An experimental model of systemic lupus erythematosus has recently been described in normal animals. We sought to confirm and extend this model, which involved immunization of normal rabbits and mice with a peptide of Sm B/B', PPPGMRPP. This peptide is an early target of the immune response in anti-Sm-positive patients with lupus. The peptide was used in a multiple Ag peptide format, with multiple copies of PPPGMRPP bound to an inert lysine backbone. New Zealand White rabbits and A/J and C57BL/10ScSn mouse strains were immunized with PPPGMRPP-MAP. Pepscan assays were used to determine the epitope spreading of the anti-PPPGMRPP-MAP response to other octamers of SmB/B' following immunization. We obtained high titer anti-PPPGMRPP-MAP IgG responses in the New Zealand White rabbits and A/J mice. The rabbits immunized with PPPGMRPP-MAP showed varying degrees of epitope spreading, while the A/J mice showed no spreading. We observed no autoantibodies to dsDNA or other anti-nuclear autoantibodies in our animals by ELISA or immunofluorescence, although anti-nuclear autoantibodies were found by Western blotting in some of the rabbits. No evidence of clinical disease was seen in our normal animals. These data underline the difficulties often associated with the reproduction of animal models in different laboratories.
最近在正常动物中描述了一种系统性红斑狼疮的实验模型。我们试图证实并扩展该模型，该模型涉及用Sm B/B'的肽PPPGMRPP对正常兔和小鼠进行免疫。这种肽是抗Sm阳性狼疮患者免疫反应的早期靶点。该肽以多抗原肽的形式使用，多个PPPGMRPP拷贝与惰性赖氨酸主链结合。用PPPGMRPP-MAP对新西兰白兔以及A/J和C57BL/10ScSn小鼠品系进行免疫。免疫后，使用肽扫描分析来确定抗PPPGMRPP-MAP反应对SmB/B'的其他八聚体的表位扩展情况。我们在新西兰白兔和A/J小鼠中获得了高滴度的抗PPPGMRPP-MAP IgG反应。用PPPGMRPP-MAP免疫的兔子表现出不同程度的表位扩展，而A/J小鼠则未表现出表位扩展。通过ELISA或免疫荧光法，我们在动物中未观察到针对双链DNA的自身抗体或其他抗核自身抗体，尽管在一些兔子中通过蛋白质印迹法发现了抗核自身抗体。在我们的正常动物中未观察到临床疾病的迹象。这些数据强调了不同实验室在复制动物模型时经常遇到的困难。
