磷脂酶A2受体和血清抗PLA2R抗体均阴性特发性膜性肾病40例临床与病理特点分析
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摘要
目的探讨肾小球磷脂酶A2受体(PLA2R)和血清抗PLA2R抗体均阴性的特发性膜性肾病(IMN)的临床及病理特点。方法选取2015—2017年首都医科大学附属北京安贞医院肾内科经穿刺确诊的IMN,采用免疫组化法检测肾小球PLA2R,酶联免疫吸附法检测血清抗PLA2R抗体。将肾小球PLA2R和血清抗PLA2R抗体均阴性者纳入A组(40例)。应用个体匹配法从肾小球PLA2R及血清抗PLA2R抗体均阳性的IMN中随机选出与A组等数量且性别、年龄匹配的患者作为B组。收集两组的临床及实验室检查资料。分别用免疫组化法及间接免疫荧光法检测两组患者肾小球1型血小板反应蛋白7A域(THSD7A)和血清抗THSD7A抗体。结果 (1)与B组相比,A组24 h尿蛋白定量低,镜下血尿比例低,治疗缓解率高,两组比较差异有统计学意义(P<0.05)。(2) A组IgG4阳性率(45.0%)显著低于B组(85.0%)(P<0.01)。(3) A组肾小球THSD7A和血清抗THSD7A抗体阳性率分别为17.5%和7.5%。B组肾小球THSD7A及血抗THSD7A抗体均阴性。结论肾小球PLA2R及血清抗PLA2R抗体均阴性的IMN相对于均阳性的IMN 24 h尿蛋白定量少,治疗缓解率高;IMN肾小球THSD7A及血清抗THSD7A抗体阳性率低。
Objective To investigate the clinicopathological features of phospholipase A2 receptor(PLA2R) negative patents with idiopathic membranous nephropathy(IMN). Methods IMN patients diagnosed by renal biopsy were enrolled in this study. Glomerular PLA2 R deposition(GAg) and serum anti-PLA2 R antibodies(SAbs) were detected by immunohistochemical staining and enzyme linked immunosorbent assay, respectively. Patients were divided into two groups. Both GAg and SAbs were negative in patients of Group A. Patients of group B were selected from patients who were positive for GAg and SAbs and were matched with group A in gender and age. The clinical and laboratory data of the two groups were collected. Glomerular thrombospondin type-1 domaincontaining 7A(THSD7A) deposition and serum anti-THSD7 A antibody were also measured by immunohistochemical staining and indirect immunofluorescence in the two groups, respectively. Results(1) Compared with group B, patients in group A had lower levels of proteinuria, lower proportion of microscopic hematuria, higher remission rate(P<0.05). The positive rate of IgG4 in group A(45.0%) was significantly lower than that in group B(85.0%)(P<0.01).(2) The positive rate of glomerular THSD7 A deposition and serum anti-THSD7 A antibody of group A were 17.5% and 7.5%. Patients in group B showed negative THSD7 A tissue staining and antiTHSD7 A antibodies. Conclusion Compared with patients who were positive for GAg and SAbs, patients who were negative for GAg and SAbs exhibited lower levels of proteinuria and higher remission rate. The positive rate of glomerular THSD7 A deposition and serum anti-THSD7 A antibody was low in patients with IMN.
Objective To investigate the clinicopathological features of phospholipase A2 receptor(PLA2R) negative patents with idiopathic membranous nephropathy(IMN). Methods IMN patients diagnosed by renal biopsy were enrolled in this study. Glomerular PLA2 R deposition(GAg) and serum anti-PLA2 R antibodies(SAbs) were detected by immunohistochemical staining and enzyme linked immunosorbent assay, respectively. Patients were divided into two groups. Both GAg and SAbs were negative in patients of Group A. Patients of group B were selected from patients who were positive for GAg and SAbs and were matched with group A in gender and age. The clinical and laboratory data of the two groups were collected. Glomerular thrombospondin type-1 domaincontaining 7A(THSD7A) deposition and serum anti-THSD7 A antibody were also measured by immunohistochemical staining and indirect immunofluorescence in the two groups, respectively. Results(1) Compared with group B, patients in group A had lower levels of proteinuria, lower proportion of microscopic hematuria, higher remission rate(P<0.05). The positive rate of IgG4 in group A(45.0%) was significantly lower than that in group B(85.0%)(P<0.01).(2) The positive rate of glomerular THSD7 A deposition and serum anti-THSD7 A antibody of group A were 17.5% and 7.5%. Patients in group B showed negative THSD7 A tissue staining and antiTHSD7 A antibodies. Conclusion Compared with patients who were positive for GAg and SAbs, patients who were negative for GAg and SAbs exhibited lower levels of proteinuria and higher remission rate. The positive rate of glomerular THSD7 A deposition and serum anti-THSD7 A antibody was low in patients with IMN.
引文
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[13]Qin W,Beck LH Jr,Zeng C,et al.Anti-phospholipase A2 receptor antibody in membranous nephropathy[J].J Am Soc Nephrol,2011,22(6):1137-1143.
[14]R adice A,Pieruzzi F,Trezzi B,et al.Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor(PLA2R)in differentiating idiopathic membranous nephropathy(IMN)from secondary forms and other glomerular diseases[J].J Nephrol,2018,31(2):271-278.
[15]Oh YJ,Yang SH,Kim DK,et al.Autoantibodies against phospholipase A2 receptor in Korean patients with membranous nephropathy[J].PLoS One,2013,8(4):e62151.
[16]Filippone EJ.Idiopathic membranous nephropathy and IgG4:an interesting relationship[J].Clin Nephrol,2014,82(1):7-15.
[17]Iwakura T,Ohashi N,Kato A,et al.Prevalence of Enhanced Granular Expression of Thrombospondin Type-1 Domain-Containing 7A in the Glomeruli of Japanese Patients with Idiopathic Membranous Nephropathy[J].Plos One,2015,10(9):e0138841.
[18]Tomas NM,Beck LH Jr,Meyer-Schwesinger C,et al.Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy[J].N Engl J Med,2014,371(24):2277-2287.
[19]Wang J,Cui Z,Lu J,et al.Circulating Antibodies against Thrombospondin Type-I Domain-Containing 7A in Chinese Patients with Idiopathic Membranous Nephropathy[J].Clin J Am Soc Nephrol,2017,12(10):1642-1651.
[20]Hoxha E,Beck LH Jr,Wiech T,et al.An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 DomainContaining 7A-Specific Antibodies in Membranous Nephropathy[J].JAm Soc Nephrol,2017,28(2):520-531.
[21]Stahl PR,Hoxha E,Wiech T,et al.THSD7A expression in human cancer[J].Genes Chromosomes Cancer,2017,56(4):314-327.
[2]Beck LH Jr,Bonegio RG,Lambeau G,et al.M-type phospholipase A2receptor as target antigen in idiopathic membranous nephropathy[J].N Engl J Med,2009,361(1):11-21.
[3]Ruggenenti P,Debiec H,Ruggiero B,et al.Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy[J].J Am Soc Nephrol,2015,26(10):2545-2558.
[4]吕晓珍,詹思延.第四讲:病例对照研究[J].中国循证儿科杂志,2009,4(5):463-466.
[5]Ma YC.Modified Glomerular Filtration Rate Estimating Equation for Chinese Patients with Chronic Kidney Disease[J].J Ame Soc Nephrol,2006,17(10):2937-2944.
[6]Dong HR,Wang YY,Cheng XH,et al.Retrospective Study of Phospholipase A2 Receptor and IgG Subclasses in Glomerular Deposits in Chinese Patients with Membranous Nephropathy[J].Plos One,2016,11(5):e0156263.
[7]Sharma SG,Larsen CP.Tissue staining for THSD7A in glomeruli correlates with serum antibodies in primary membranous nephropathy:a clinicopathological study[J].Mod Pathol,2018,31(4):616-622.
[8]Kidney Disease:Improving Global Outcomes(KDIGO)Glomerulonephritis Work Group.KDIGO clinical practice guideline for glomerulonephritis[J].Kidney Int Suppl,2012,2:186-197.
[9]王茂斌,北京医师协会.临床医疗护理常规[M].北京:中国医药科技出版社,2012:1-368.
[10]Hoxha E,Knei?ler U,Stege G,et al.Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy[J].Kidney Int,2012,82(7):797-804.
[11]Qin HZ,Zhang MC,Le WB,et al.Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous Nephropathy[J].J Am Soc Nephrol,2016,27(10):3195-3203.
[12]Hihara K,Iyoda M,Tachibana S,et al.Anti-Phospholipase A2 Receptor(PLA2R)Antibody and Glomerular PLA2R Expression in Japanese Patients with Membranous Nephropathy[J].PLoS One,2016,11(6):e0158154.
[13]Qin W,Beck LH Jr,Zeng C,et al.Anti-phospholipase A2 receptor antibody in membranous nephropathy[J].J Am Soc Nephrol,2011,22(6):1137-1143.
[14]R adice A,Pieruzzi F,Trezzi B,et al.Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor(PLA2R)in differentiating idiopathic membranous nephropathy(IMN)from secondary forms and other glomerular diseases[J].J Nephrol,2018,31(2):271-278.
[15]Oh YJ,Yang SH,Kim DK,et al.Autoantibodies against phospholipase A2 receptor in Korean patients with membranous nephropathy[J].PLoS One,2013,8(4):e62151.
[16]Filippone EJ.Idiopathic membranous nephropathy and IgG4:an interesting relationship[J].Clin Nephrol,2014,82(1):7-15.
[17]Iwakura T,Ohashi N,Kato A,et al.Prevalence of Enhanced Granular Expression of Thrombospondin Type-1 Domain-Containing 7A in the Glomeruli of Japanese Patients with Idiopathic Membranous Nephropathy[J].Plos One,2015,10(9):e0138841.
[18]Tomas NM,Beck LH Jr,Meyer-Schwesinger C,et al.Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy[J].N Engl J Med,2014,371(24):2277-2287.
[19]Wang J,Cui Z,Lu J,et al.Circulating Antibodies against Thrombospondin Type-I Domain-Containing 7A in Chinese Patients with Idiopathic Membranous Nephropathy[J].Clin J Am Soc Nephrol,2017,12(10):1642-1651.
[20]Hoxha E,Beck LH Jr,Wiech T,et al.An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 DomainContaining 7A-Specific Antibodies in Membranous Nephropathy[J].JAm Soc Nephrol,2017,28(2):520-531.
[21]Stahl PR,Hoxha E,Wiech T,et al.THSD7A expression in human cancer[J].Genes Chromosomes Cancer,2017,56(4):314-327.
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