Detection of antigen in bronchial epithelium and macrophages in acute Kawasaki disease by use of synthetic antibody
Detection of antigen in bronchial epithelium and macrophages in acute Kawasaki disease by use of synthetic antibody
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DOI：
10.1086/422648
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发表时间：
2004-08-15
影响因子：
6.4
通讯作者：
Crawford, SE
中科院分区：
文献类型：
--
作者：
Rowley, AH;Baker, SC;Crawford, SE
背景川崎是发达国家儿童最常见的获得性心脏病。病因不明，但可能是一种普遍存在的感染因子。免疫球蛋白A浆细胞浸润急性KD炎症组织，产生寡克隆抗原驱动抗体。为了鉴定KD发病机制中的重要抗原，体外制备了KD寡克隆抗体，并通过免疫组化实验对急性KD患者和对照组的组织进行了检测，还检测了与人类炎症蛋白的反应性。通过使用合成抗体A，在13例急性KD患者中的10例中观察到与近端支气管上皮细胞质抗原的特异性结合，而在9例对照受试者中观察到0例（P = .001）。巨噬细胞亚群在所有17例急性KD患者的至少1个炎症组织中呈阳性。在12支急性KD冠状动脉瘤中有9支检测到抗原，而在10支对照冠状动脉中没有检测到抗原（P <0.001）。该抗原不是免疫球蛋白或任何40种常见的炎性蛋白。我们报告的第一个演示的KD相关抗原的组织靶向的疾病。我们的研究结果与KD是由一种以前未鉴定的呼吸道感染因子引起的、对血管组织具有嗜性的理论是一致的。
Background. Kawasaki disease (KD) is the most common acquired cardiac disease in children in developed nations. The etiology is unknown, but a ubiquitous infectious agent appears to be likely. Immunoglobulin A plasma cells infiltrate inflamed tissues in acute KD, producing oligoclonal, antigen-driven antibodies.Methods. To identify antigens important in the pathogenesis of KD, oligoclonal KD antibodies were prepared in vitro and tested by immunohistochemistry experiments on tissues from patients with acute KD and from control subjects and were also tested for reactivity with human inflammatory proteins.Results. By use of synthetic antibody A, specific binding to a cytoplasmic antigen in proximal bronchial epithelium was observed in 10 of 13 patients with acute KD but in 0 of 9 control subjects (P = .001). A subset of macrophages was positive in at least 1 inflamed tissue from all 17 patients with acute KD. Antigen was detected in 9 of 12 acute KD coronary artery aneurysms but in 0 of 10 control coronary arteries (P < .001). The antigen is not immunoglobulin or any of 40 common inflammatory proteins.Conclusions. We report the first demonstration of a KD-associated antigen in the tissues targeted by the disease. Our findings are consistent with the theory that KD is caused by a previously unidentified respiratory infectious agent with tropism for vascular tissue.