Gordon L K, Eggena M, Targan S R, Braun J
Department of Ophthalmology, University of California, Los Angeles, California 90095, USA.
Clin Immunol. 2000 Jan;94(1):42-50. doi: 10.1006/clim.1999.4805.
pANCA is a marker antibody expressed in most patients with ulcerative colitis, and its cognate antigen is potentially an immunologic target in this disease. This study evaluates whether pANCA detects an autoantigen that is expressed in the colonic mucosa. Immunohistochemistry of colon specimens with human pANCA monoclonal antibodies (Fab 5-2 and 5-3) revealed a minor population of immunoreactive mucosal cells bearing a cytoplasmic vesicle antigen. By distribution, morphology, and tryptase expression, these were identified as mast cells. Immunofluorescent analysis revealed similar immunoreactivity of mouse mast cell lines and human KU812. Western analysis of mouse mast cell lines revealed immunoreactive proteins, and these were distinct from previously proposed pANCA antigens (histone H1, HMG 1 and 2, and neutrophil vesicle antigens). Cognate antigen for Fab 5-2 and 5-3 was also expressed in other tissue mast cells, cerebellar neurons, and pancreatic islet cells. These findings identify a novel cytoplasmic autoantigen(s) associated with UC by its presence in colonic mucosa and recognition by a disease-associated marker antibody.
核周型抗中性粒细胞胞浆抗体（pANCA）是大多数溃疡性结肠炎患者体内表达的一种标记性抗体，其同源抗原可能是该疾病的一个免疫靶点。本研究评估pANCA是否能检测出在结肠黏膜中表达的自身抗原。用人pANCA单克隆抗体（Fab 5-2和5-3）对结肠标本进行免疫组织化学分析，发现少数免疫反应性黏膜细胞带有细胞质囊泡抗原。通过分布、形态和类胰蛋白酶表达，这些细胞被鉴定为肥大细胞。免疫荧光分析显示小鼠肥大细胞系和人KU812有类似的免疫反应性。对小鼠肥大细胞系进行蛋白质印迹分析，发现了免疫反应性蛋白，且这些蛋白与先前提出的pANCA抗原（组蛋白H1、高迁移率族蛋白1和2以及中性粒细胞囊泡抗原）不同。Fab 5-2和5-3的同源抗原在其他组织肥大细胞、小脑神经元和胰岛细胞中也有表达。这些发现通过其在结肠黏膜中的存在以及被疾病相关标记抗体识别，确定了一种与溃疡性结肠炎相关的新型细胞质自身抗原。
