Das K M, Vecchi M, Squillante L, Dasgupta A, Henke M, Clapp N
Department of Medicine, UMDNJ Robert Wood Johnson Medical School, New Brunswick 08903.
Gut. 1992 Jan;33(1):48-54. doi: 10.1136/gut.33.1.48.
Saguinus oedipus, Callithrix jacchus, and Saguinus fuscicollis are three species of New World monkeys which develop a form of colitis that is similar to human ulcerative colitis. Only S oedipus, however, develop colon cancer. We examined intestinal tissues from these animals for the presence of an antigen cross reacting to the Mr 40,000 human colonic epithelial protein that acts as an autoantigen in ulcerative colitis. Using an anti-Mr 40,000 monoclonal antibody (7E12H12, IgM isotype), by an immunoperoxidase assay we showed that all colon specimens from S oedipus reacted with 7E12H12; however, the colonic tissue from C jacchus and S fuscicollis did not. In immunotransblot analysis eluted IgG antibody bound to human ulcerative colitis colon (CCA-IgG) reacted with Mr 40,000 protein(s) present in the extracts of colon from S oedipus animals and humans. Small intestinal tissue reacted neither with 7E12H12 nor with CCA-IgG. In S oedipus, the Mr 40,000 protein was localised exclusively to colonic epithelial cells. Preincubation of seven S oedipus colon specimens with eight of 10 sera from animals with acute or chronic colitis and 0 of four sera from animals without colitis almost completely inhibited the binding of 7E12H12 to the colonic epithelium. Four of these 10 sera inhibited the binding of 7E12H12 to the autologous colon. These results show the presence of circulating autoantibodies in S oedipus with colitis against an epitope(s) on Mr 40,000 protein shared by human and S oedipus colon.
普通棉耳狨、白喉卷尾猴和褐颈卷尾猴是三种新大陆猴,它们会患上一种与人类溃疡性结肠炎相似的结肠炎。然而,只有普通棉耳狨会患结肠癌。我们检查了这些动物的肠道组织,以寻找与分子量为40000的人类结肠上皮蛋白发生交叉反应的抗原,该蛋白在溃疡性结肠炎中作为自身抗原。使用抗分子量40000单克隆抗体(7E12H12,IgM同型),通过免疫过氧化物酶测定,我们发现普通棉耳狨的所有结肠标本都与7E12H12发生反应;然而,白喉卷尾猴和褐颈卷尾猴的结肠组织则没有。在免疫印迹分析中,与人类溃疡性结肠炎结肠结合的洗脱IgG抗体(CCA-IgG)与普通棉耳狨和人类结肠提取物中存在的分子量40000蛋白发生反应。小肠组织既不与7E12H12反应,也不与CCA-IgG反应。在普通棉耳狨中,分子量40000蛋白仅定位于结肠上皮细胞。用来自患有急性或慢性结肠炎动物的10份血清中的8份对7份普通棉耳狨结肠标本进行预孵育,而来自无结肠炎动物的4份血清中0份能几乎完全抑制7E12H12与结肠上皮的结合。这10份血清中有4份抑制了7E12H12与自身结肠的结合。这些结果表明,患有结肠炎的普通棉耳狨体内存在针对人类和普通棉耳狨结肠共有的分子量40000蛋白上的一个或多个表位的循环自身抗体。