Snook J A, Chapman R W, Fleming K, Jewell D P
Department of Gastroenterology, John Radcliffe Hospital, Oxford, UK.
Clin Exp Immunol. 1989 Apr;76(1):30-3.
We have previously described circulating autoantibodies to a portal tract antigen in patients with primary sclerosing cholangitis. In this study the antigen has been shown by double-labelling studies to be specifically located in the nuclei of tissue neutrophils. Using isolated peripheral blood neutrophils and an immunoperoxidase technique, anti-neutrophil nuclear antibody (ANNA) was found in the serum of 84% of patients with primary sclerosing cholangitis (PSC: n = 32) with a median titre of 1/1000 and a peak titre of 1/500,000. ANNA was also detected in 86% of patients with inflammatory bowel disease alone (IBD: n = 76) with a median titre of 1/10 and a peak titre of 1/10,000. In contrast, only 12% of controls had ANNA, and in none was the titre greater than 1/10. In PSC the ANNA titre correlated with the serum aspartate transaminase concentration, suggesting that it is related to disease activity. In IBD the titre of ANNA was significantly higher in patients with recently active disease. There was no significant difference between the titres seen in ulcerative colitis and Crohn's disease. ANNA was not associated with neutropaenia. The results provide further evidence of involvement of autoimmune mechanisms in inflammatory bowel disease and primary sclerosing cholangitis.
我们之前曾描述过原发性硬化性胆管炎患者体内存在针对门管区抗原的循环自身抗体。在本研究中,通过双重标记研究表明该抗原特异性定位于组织中性粒细胞的细胞核中。使用分离的外周血中性粒细胞和免疫过氧化物酶技术,在84%的原发性硬化性胆管炎(PSC:n = 32)患者血清中发现了抗中性粒细胞核抗体(ANNA),中位滴度为1/1000,峰值滴度为1/500,000。在仅患有炎症性肠病(IBD:n = 76)的患者中,86%也检测到了ANNA,中位滴度为1/10,峰值滴度为1/10,000。相比之下,只有12%的对照者有ANNA,且无一例滴度大于1/10。在PSC中,ANNA滴度与血清天冬氨酸转氨酶浓度相关,表明其与疾病活动有关。在IBD中,近期疾病活动的患者ANNA滴度明显更高。溃疡性结肠炎和克罗恩病患者的滴度之间没有显著差异。ANNA与中性粒细胞减少无关。这些结果为自身免疫机制参与炎症性肠病和原发性硬化性胆管炎提供了进一步的证据。