摘要
目的 研究丙基硫氧嘧啶 (PTU)引起的抗中性粒细胞胞质抗体 (ANCA)阳性小血管炎的临床病理表现及其靶抗原。方法 对我院近年诊治的 4例PTU引起的ANCA阳性小血管炎患者进行临床病理分析。以纯化的 7种已知的ANCA靶抗原蛋白酶 3(PR3)、髓过氧化物酶 (MPO)、人白细胞弹力蛋白酶 (HLE)、乳铁蛋白 (LF)、组蛋白酶G(CG)、杀菌 /通透性增高蛋白 (BPI)和天青杀素 (AZU)为固相抗原 ,采用ELISA法检测患者血清的靶抗原及治疗前后抗体滴度的变化。结果 4例病人中男女各 2例 ,平均年龄 30 (11～ 5 7)岁 ,服PTU时间 7～ 6 0个月。 4例均有肾脏、肺脏、皮肤、关节肌肉和血液系统等受累 ,均为p ANCA阳性 ,患者血清均识别MPO、LF和CG ;3例识别HLE、AZU ,2例识别PR3;无1例识别BPI。多数抗体滴度高 ,可大于 1∶2 5 6 0 0 ;而服PTU无小血管炎临床表现的甲状腺功能亢进(甲亢 )病人的 30份血清均为阴性。肾活检 2例为新月体性肾炎 ,2例为轻微病变 ,免疫荧光检查均为阴性。 4例患者均立即停用PTU ,3例应用免疫抑制剂 ,1例行血浆置换。 4例小血管炎的临床症状均得以缓解 ,但 1例晚期新月体肾炎患者发展为慢性肾衰竭而依赖透析。停药和治疗后各种抗体滴度均有所下降 ,但多未能短期阴转。结论 PTU可引起ANCA阳性小血管炎 。
Objective To study the clinicopathological manifestations and target antigens of propylthiouracil (PTU) induced antineutrophil cytoplasmic antibody (ANCA) positive vasculitis. Methods 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). Results Four patients with Grave′s disease, 2 female and 2 male with a mean age of 30 (11～57) years who had been treated with PTU for 7～60 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 dependedent. 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. Conclusions 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.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2002年第6期404-407,共4页
Chinese Journal of Internal Medicine
