抗磷脂酶A受体抗体与特发性膜性肾病.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,抗磷脂酶,A2,受体抗体,与特发性膜性肾病,秦卫松,南京军区南京总医院,全军肾脏病研究所 全军肾脏病重点实验室,研究背景,研究方法,结论,persistent or relapse of proteinuria despite resection of the tumor.,Glassock RJ.,Table Anti-PLA2R in Chinese patients with membranous nephropathy,SDS-PAGE(Non-reduced),经抗病毒治疗后患者尿蛋白部分缓解或完全缓解；,N Engl J Med,361:81,2 patients:complete remission of the proteinuria after tumor resection;,乙肝两对半检测显示大三阳和/或HBV-DNA阳性；,Anti-PLA2R in IMN and IMN with complete remission,Low titer of anti-PLA2R existed in 10 of remaining 11 negative IMN.,经抗病毒治疗后患者尿蛋白部分缓解或完全缓解；,Detection of anti-PLA2R in idiopathic MN,N Engl J Med ;361:11,The remaining 2 patients had persistent proteinuria without tumor resection.,Detection of anti-PLA2R in idiopathic MN,研究背景,Beck Jr LH,et al.N Engl J Med ;361:11,Western Blotting of Glomerular Proteins with Serum,from Patients with IMN.,2 patients:complete remission of the proteinuria after tumor resection;,经肾活检病理明确诊断为肾小球膜性病变，,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：60例,Glassock RJ.,经肾活检病理明确诊断为肾小球膜性病变，,免疫荧光以IgG、C3为主,C1q阴性；,V型狼疮性肾炎：20例,Table Anti-PLA2R in Chinese patients with membranous nephropathy,经抗病毒治疗后患者尿蛋白部分缓解或完全缓解；,Detection of anti-PLA2R in idiopathic MN,特发性膜性肾病治疗后缓解的病例：21例,Low titer of anti-PLA2R in negative idiopathic MN,Laurence H.,SDS-PAGE(Non-reduced),抗磷脂酶A2受体抗体与特发性膜性肾病,Glassock RJ.N Engl J Med,361:81,病例选择,特发性膜性肾病,：,60,例,肾活检时尿蛋白定量,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,：,21,例,病例选择,V,型狼疮性肾炎,：,20,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,，尿沉渣红细胞,100,万,/ml,。,乙肝相关膜性肾病,：,16,例,经肾活检病理明确诊断为肾小球膜性病变；,乙肝两对半检测显示大三阳和,/,或,HBV-DNA,阳性；,肾组织乙肝抗原染色阳性,(,其中,HBeAg,必须阳性,),；,经抗病毒治疗后患者尿蛋白部分缓解或完全缓解；,肾活检时尿蛋白定量,。,肿瘤相关膜性肾病,：,10,例,肾活检时尿蛋白定量,从肾小球提取蛋白抗原,SDS-PAGE(Non-reduced),转印至硝酸纤维素膜,与患者血清孵育（,1,：,25,）,一抗，二抗，显色,实验方法,研究结果,Detection of anti-PLA2R in idiopathic MN,Recognition of idiopathic MN serum with deglycosylated PLA2R,The prevalence of anti-PLA2R in idiopathic MN and secondary MN,n,Anti-PLA2R,%,Idiopathic MN,60,49,81.7%,Lupus MN,20,1,5.0%,HBV-MN,16,1,6.3%,Tumor-MN,10,3,30%,Table Anti-PLA2R 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 MN,Low titer of anti-PLA2R existed in 10 of remaining 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 activity,Anti-PLA2R in IMN and IMN with complete remission,81.7%,19.0%,结 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性肾病诊断和疗效判断的特异标志物。,致 谢,刘志红院士,David J.Salant,Laurence H.Beck,Jr.,陈朝红,曾彩虹,左科,IgG4 in a glomerulus of a patient with tumor-MN but without circulating anti-PLA2R antibodies.,Bright IgG4 in a glomerulus of a patient with tumor-MN and circulating anti-PLA2R antibodies.,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,