Asada Masanori, Nishio Akiyoshi, Uchida Kazushige, Kido Masahiro, Ueno Satoru, Uza Norimitsu, Kiriya Keiichi, Inoue Satoko, Kitamura Hiroshi, Ohashi Shinya, Tamaki Hiroyuki, Fukui Toshiro, Matsuura Minoru, Kawasaki Kimio, Nishi Toshiki, Watanabe Norihiko, Nakase Hiroshi, Chiba Tsutomu, Okazaki Kazuichi
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Pancreas. 2006 Jul;33(1):20-6. doi: 10.1097/01.mpa.0000226881.48204.fd.
Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis of the disease remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not in about 10%. We undertook this study to determine whether additional autoantibodies are present in the serum level of AIP patients.
We recruited 26 patients with AIP for the study. For comparison, we also recruited 53 patients with various pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic cDNA library using patients' sera. Positive clones were analyzed by DNA sequencing and were constructed into a pGEX-4T-1 expression vector. The recombinant proteins were used as antigens in enzyme-linked immunosorbent assay to screen the subjects' sera for autoantibodies.
We cloned a cDNA encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%) by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay, respectively. However, none of control subjects was positive for anti-PSTI antibodies.
These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease.
尽管自身免疫性胰腺炎(AIP)最近已被确认为慢性胰腺炎的一种新的疾病实体,但该疾病的临床诊断仍存在争议。大多数AIP患者可检测到抗碳酸酐酶II和乳铁蛋白的自身抗体,但约10%的患者检测不到。我们进行这项研究以确定AIP患者血清中是否存在其他自身抗体。
我们招募了26例AIP患者进行研究。为作比较,我们还招募了53例患有各种胰腺疾病的患者和12名健康受试者。我们用患者血清对人胰腺cDNA文库进行免疫筛选。对阳性克隆进行DNA测序分析,并构建到pGEX-4T-1表达载体中。重组蛋白用作酶联免疫吸附测定中的抗原,以筛选受试者血清中的自身抗体。
我们克隆了一个编码胰腺分泌性胰蛋白酶抑制剂(PSTI)的cDNA。在26例AIP患者中,通过蛋白质印迹法检测到抗PSTI自身抗体呈阳性的有11例(42.3%),通过酶联免疫吸附测定呈阳性的有8例(30.8%)。然而,对照组受试者中抗PSTI抗体均为阴性。
这些发现表明PSTI可能与AIP的发病机制有关,抗PSTI自身抗体可作为该疾病有用的诊断标志物。