Xu Xudong, Zhao Minghui, Zhang Youkang, Guo Xiaohui, Wang Haiyan
Department of Nephrology, The First Hospital, Peking University, Beijing 100034, China.
Zhonghua Nei Ke Za Zhi. 2002 Jun;41(6):404-7.
To study the clinicopathological manifestations and target antigens of propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA) positive vasculitis.
Four hospitalized patients with PTU-induced ANCA positive vasculitis in recent two years were studied. Target antigens and antibody titers were investigated with ELISA using seven highly purified known ANCA antigens as solid phase ligands. The known antigens included proteinase 3 (PR3), myeloperoxidase (MPO), human leukocyte elastase (HLE), lactoferrin (LF), cathepsinG (CG), bactericidal/permeability-increasing protein (BPI) and azurocidin (AZU).
Four patients with Grave's disease, 2 female and 2 male with a mean age of 30 (11 approximately 57) years who had been treated with PTU for 7 approximately 60 months suffered from ANCA positive vasculitis. All the 4 patients had renal, lung, skin, joint, muscle and hematological involvement. Sera from all the 4 patients were ANCA positive and recognized MPO, LF and CG. Sera from 3 patients recognized HLE and AZU and 2 recognized PR3. None of the sera recognized BPI. The majority of the autoantibodies had high titers >/= 1:25 600. All the sera from 30 patients with Grave's disease and PTU treatment but without vasculitis were ANCA negative. All the 4 patients had pauci- immune glomerular lesions in renal biopsy; 2 had crescentic glomerulonephritis and the remaining 2 had minor glomerular abnormalities. All the 4 patients responded to withdrawal of propylthiouracil; 3 patients were treated with immunosuppressive agents. All the patients achieved clinical remission. However, one patient with crescentic glomerulonephritis was dialysis dependent. After withdrawal of PTU and administration of immunosuppressants, ANCA titres declined, but did not turn to negative in 1-6 months in most of the patients.
PTU can induce ANCA positive vasculitis. The autoantibodies were polyclonal and recognized multiple target antigens of neutrophil cytoplasm. Early withdrawal of PTU and administration of immunosuppressive agents might improve the prognosis.
研究丙硫氧嘧啶（PTU）诱导的抗中性粒细胞胞浆抗体（ANCA）阳性血管炎的临床病理表现及靶抗原。
对近两年来4例住院的PTU诱导的ANCA阳性血管炎患者进行研究。以7种高度纯化的已知ANCA抗原作为固相配体，采用酶联免疫吸附测定（ELISA）法检测靶抗原及抗体滴度。已知抗原包括蛋白酶3（PR3）、髓过氧化物酶（MPO）、人白细胞弹性蛋白酶（HLE）、乳铁蛋白（LF）、组织蛋白酶G（CG）、杀菌/通透性增加蛋白（BPI）和天青杀素（AZU）。
4例格雷夫斯病患者，2例女性，2例男性，平均年龄30（11～57）岁，接受PTU治疗7～60个月，发生ANCA阳性血管炎。4例患者均有肾脏、肺、皮肤、关节、肌肉及血液系统受累。4例患者血清ANCA均为阳性，且均识别MPO、LF和CG。3例患者血清识别HLE和AZU，2例识别PR3。无一例血清识别BPI。大多数自身抗体滴度较高，≥1:25 600。30例接受PTU治疗但无血管炎的格雷夫斯病患者血清ANCA均为阴性。4例患者肾活检均有寡免疫性肾小球病变；2例为新月体性肾小球肾炎，其余2例有轻微肾小球异常。4例患者停用丙硫氧嘧啶后均有反应；3例患者接受免疫抑制剂治疗。所有患者均达到临床缓解。然而，1例新月体性肾小球肾炎患者依赖透析。停用PTU并给予免疫抑制剂后，ANCA滴度下降，但大多数患者在1～6个月内未转阴。
PTU可诱导ANCA阳性血管炎。自身抗体为多克隆性，识别中性粒细胞胞浆的多种靶抗原。早期停用PTU并给予免疫抑制剂可能改善预后。
