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1、抗磷脂酶抗磷脂酶A2受体抗体受体抗体与特发性膜性肾病与特发性膜性肾病秦卫松秦卫松南京军区南京总医院南京军区南京总医院全军肾脏病研究所全军肾脏病研究所 全军肾脏病重点实验室全军肾脏病重点实验室 研究背景研究背景 研究方法研究方法 结论结论研究背景研究背景Beck Jr LH, et al. N Engl J Med 2009; 361: 11Western Blotting of Glomerular Proteins with Serumfrom Patients with IMN.Glassock RJ. N Engl J Med,2009,361: 81病例选择病例选择特发性膜性肾病特发性
2、膜性肾病：60例例 肾活检时尿蛋白定量3.5g/24hr 经肾活检病理明确诊断为肾小球膜性病变， 光镜观察无内皮或系膜细胞增殖，无内皮下嗜复红物沉积， 免疫荧光以IgG、C3为主, C1q阴性； 自身抗体检测阴性，无乙肝、丙肝感染、肿瘤病史，无重金属、有机溶剂接触史；特发性膜性肾病治疗后缓解的病例特发性膜性肾病治疗后缓解的病例：21例例病例选择病例选择 V型狼疮性肾炎型狼疮性肾炎：20例例系统性红斑狼疮、狼疮性肾炎诊断明确；病理上以V型（膜性）病变为主，免疫荧光以颗粒状上皮侧沉积为主，无明显系膜或内皮细胞增殖；肾活检时尿蛋白定量3.5g/24hr，尿沉渣红细胞3.5g/24hr。 肿瘤相关膜性
3、肾病肿瘤相关膜性肾病：10例肾活检时尿蛋白定量3.5g/24hr从肾小球提取蛋白抗原从肾小球提取蛋白抗原SDS-PAGE (Non-reduced)转印至硝酸纤维素膜转印至硝酸纤维素膜与患者血清孵育（与患者血清孵育（1：25）一抗，二抗，显色一抗，二抗，显色实验方法实验方法研究结果研究结果 Detection of anti-PLA2R in idiopathic MNRecognition of idiopathic MN serum with deglycosylated Recognition of idiopathic MN serum with deglycosylated PLA2
4、RPLA2RThe prevalence of anti-PLA2R in idiopathic MN The prevalence of anti-PLA2R in idiopathic MN and secondary MNand secondary MNn nAnti-PLA2RAnti-PLA2R%Idiopathic MNIdiopathic MN6060494981.7%81.7%Lupus MNLupus MN20201 15.0%5.0%HBV-MNHBV-MN16161 16.3%6.3%Tumor-MNTumor-MN10103 330%30%Table Anti-PLA2
5、R in Chinese patients with membranous nephropathy There was an absence of immunologic disease activity at the time when their serum was sampled, despite proteinuria.Why remain 11 IMN patients negative?Low titer of anti-PLA2R in negative idiopathic MNLow titer of anti-PLA2R existed in 10 of remaining
6、 11 negative IMN.PC: a MN serum that was positive under standard conditions diluted to 1:1000. HC, Healthy control, serum from healthy adult (1:10). Association of anti-PLA2R with disease activityAnti-PLA2R in IMN and IMN with complete remission81.7%19.0%结结 论论PLA2R 是中国人特发性膜性肾病的重要靶抗原。抗PLA2R抗体可以作为特发性膜
7、性肾病诊断和疗效判断的特异标志物。致致 谢谢刘志红院士刘志红院士 David J. Salant Laurence H. Beck, Jr. 陈朝红陈朝红曾彩虹曾彩虹左科左科A. IgG4 in a glomerulus of a patient with tumor-MN but without circulating anti-PLA2R antibodies. B. Bright IgG4 in a glomerulus of a patient with tumor-MN and circulating anti-PLA2R antibodies. IgG4 deposition in
8、 glomeruli of tumor-MN. IgG4 deposition in glomeruli of tumor-MN.All three patients with Anti-PLA2R : persistent or relapse of proteinuria despite resection of the tumor. In those patients without anti-PLA2R: 2 patients: complete remission of the proteinuria after tumor resection; 3 patients died of cancer; The remaining 2 patients had persistent proteinuria without tumor resection.Follow-up of tumor-MN
抗磷脂酶A2受体抗体与特发性膜性肾病
