Ma W, Ozaki S, Sobajima J, Uesugi H, Murakami M, Tanaka M, Kozuki M, Hashimoto H, Fujita Y, Kawabata D, Osakada F, Shirakawa H, Yoshida M, Hayami M, Nakao K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Autoimmunity. 2000 Dec;32(4):281-91. doi: 10.3109/08916930008994102.
Anti-neutrophil cytoplasmic antibodies (ANCA) have been widely studied and recognized to be clinically very important for some human diseases including systemic rheumatic diseases. We analyzed ANCA response and their target antigens in MRL/Mp-lpr/lpr (MRL-lpr) mice, an animal model of systemic rheumatic disease. P-ANCA was detected in 57% of the mice. Antibodies to the known P-ANCA target antigens at the same age were examined. Among these, antibodies to high mobility group (HMG) proteins HMG1 and HMG2 were detected in 57% of the mice, 75% of which were also positive for P-ANCA. These anti-HMG1/HMG2 activities were absorbed by preincubation with a mixture of HMG1 and HMG2. In contrast, antibodies to myeloperoxidase and cathepsin G were detected in 14% and 7%, respectively, but these activities were not inhibited by preincubation with corresponding antigens. In addition, the titers of P-ANCA and anti-HMG1/HMG2 antibodies in MRL-lpr mice were significantly correlated with each other. Thus, HMG1 and HMG2 were considered to be significant target antigens of P-ANCA in MRL-lpr mice.
抗中性粒细胞胞浆抗体（ANCA）已得到广泛研究，并被认为在包括系统性风湿性疾病在内的一些人类疾病中具有重要临床意义。我们分析了MRL/Mp-lpr/lpr（MRL-lpr）小鼠（一种系统性风湿性疾病动物模型）中的ANCA反应及其靶抗原。57%的小鼠检测到P-ANCA。检测了相同年龄小鼠针对已知P-ANCA靶抗原的抗体。其中，57%的小鼠检测到针对高迁移率族（HMG）蛋白HMG1和HMG2的抗体，其中75%的小鼠P-ANCA也呈阳性。这些抗HMG1/HMG2活性通过与HMG1和HMG2的混合物预孵育而被吸收。相比之下，分别有14%和7%的小鼠检测到针对髓过氧化物酶和组织蛋白酶G的抗体，但这些活性不受与相应抗原预孵育的抑制。此外，MRL-lpr小鼠中P-ANCA和抗HMG1/HMG2抗体的滴度彼此显著相关。因此，HMG1和HMG2被认为是MRL-lpr小鼠中P-ANCA的重要靶抗原。
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