中国医科大学学报

中国医科大学学报
  • 中文核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
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中国医科大学学报 ›› 2017, Vol. 46 ›› Issue (12): 1133-1137.doi: 10.12007/j.issn.0258-4646.2017.12.016

• 综述 • 上一篇    下一篇

补体系统与IgA肾病

朱林波, 郑建楠, 刘林林   

  1. 中国医科大学附属第一医院肾内科, 沈阳 110001
  • 收稿日期:2017-04-14 出版日期:2017-12-30 发布日期:2017-12-08
  • 通讯作者: 刘林林 E-mail:catherine-ll@126.com
  • 作者简介:朱林波(1990-),男,硕士研究生.
  • 基金资助:
    国家自然科学基金(81500525);辽宁省自然科学基金(2014021046)

Complement System and Immunoglobulin A Nephropathy

ZHU Linbo, ZHENG Jiannan, LIU Linlin   

  1. Department of Nephrology, The First Hospital, China Medical University, Shenyang 110001, China
  • Received:2017-04-14 Online:2017-12-30 Published:2017-12-08

摘要: IgA肾病被认为是一种免疫介导的炎症性疾病,但其发病及进展机制尚未完全明确。目前认为IgA肾病的可能机制为糖基化缺陷的IgA1增多,与抗聚糖抗体结合为免疫复合物,沉积于肾小球系膜区,进而激活补体途径,导致免疫炎症反应。补体激活的替代途径、凝集素途径、补体成分以及补体调节蛋白在IgA肾病的发病及进展过程中发挥重要作用。肾组织、尿液、血清中补体成分及其调节因子的检测可望作为IgA肾病病情活动及判断预后的标志物。全基因组关联分析等新技术手段的应用有助于深入研究IgA肾病中补体系统的作用及机制,使其成为IgA肾病新的治疗靶点。

关键词: IgA肾病, 补体系统激活

Abstract: Although immunoglobulin A (IgA) nephropathy (IgAN) is considered as an immune-mediated inflammatory disease,the pathogenesis and mechanisms associated with its progression have not been completely understood. To date,the potential pathogenesis of IgAN is thought to be a possible increase of galactose-deficient IgA1,followed by binding to antiglycan antibodies to form immune complexes,which are deposited in the glomerular mesangium and lead to the activation of complement pathways and initiation of immune-mediated inflammation. Activation of alternative and lectin complement pathways,complement components,and complement regulatory proteins play important roles in the pathogenesis and progression of IgAN. Complement components and complement regulatory factors in the renal tissue,urine,and serum samples are considered to be useful predictive biomarkers to evaluate the activation of the complement system and determine the prognosis of IgAN. The application of novel techniques such as the genome-wide association study would promote further research to determine the role and mechanisms of action of the complement system,whereby it could be used as a new therapeutic target for the management of IgAN.

Key words: immunoglobulin A nephropathy, complement systems activation

中图分类号: 

  • R692.3
[1] WYATT RJ,JULIAN BA. IgA nephropathy[J]. N Engl J Med,2013,368(25):2402-2414. DOI:10.1056/NEJMra1206793.
[2] MAGISTRONI R,D AGATI VD,APPEL GB,et al. New developments in the genetics,pathogenesis,and therapy of IgA nephropathy[J]. Kidney Int,2015,88(5):974-989. DOI:10.1038/ki.2015.252.
[3] AL HUSSAIN T,HUSSEIN MH,AL MANA H,et al. Pathophysiology of IgA nephropathy[J]. Adv Anat Pathol,2017,24(1):56-62.
[4] LEE HJ,CHOI SY,JEONG KH,et al. Association of C1q deposition with renal outcomes in IgA nephropathy[J]. Clin Nephrol,2013,80(2):98-104. DOI:10.5414/CN107854.
[5] NASRI H,MORTAZAVI M,GHORBANI A,et al. Oxford-MEST classification in IgA nephropathy patients:a report from Iran[J]. J Nephropathol,2012,1(1):31-42. DOI:10.5812/jnp.7.
[6] ROBERTS IS,COOK HT,TROYANOV S,et al. The Oxford classification of IgA nephropathy:pathology definitions,correlations,and reproducibility[J]. Kidney Int,2009,76(5):546-556. DOI:10.1038/ki.2009.168.
[7] SUZUKI H,OHSAWA I,KODAMA F,et al. Fluctuation of serum C3 levels reflects disease activity and metabolic background in patients with IgA nephropathy[J]. J Nephrol,2013,26(4):708-715. DOI:10.5301/jn.5000278.
[8] LIU L,ZHANG Y,DUAN X,et al. C3a,C5a renal expression and their receptors are correlated to severity of IgA nephropathy[J]. J Clin Immunol,2014,34(2):224-232. DOI:10.1007/s10875-013-9970-6.
[9] HIEMSTRA PS,GORTER A,STUURMAN ME,et al. Activation of the alternative pathway of complement by human serum IgA[J]. Eur J Immunol,1987,17(3):321-326.
[10] SCHMITT R,STAHL AL,OLIN AI,et al. The combined role of galactose-deficient IgA1 and streptococcal IgA-binding M protein in inducing IL-6 and C3 secretion from human mesangial cells:implications for IgA nephropathy[J]. J Immunol,2014,193(1):317-326. DOI:10.4049/jimmunol.1302249.
[11] LIU LL,LIU N,CHEN Y,et al. Glomerular mannose-binding lectin deposition is a useful prognostic predictor in immunoglobulin A nephropathy[J]. Clin Exp Immunol,2013,174(1):152-160. DOI:10.1111/cei.12154.
[12] ROOS A,RASTALDI MP,CALVARESI N,et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease[J]. J Am Soc Nephrol,2006,17(6):1724-1734. DOI:10.1111/cei.12154.
[13] 刘林林, 刘楠, 王娟, 等. 肾小球C4d沉积为IgA肾病的预后因子[J]. 中国医科大学学报, 2017, 46(1):23-27. DOI:10.12007/j. issn.0258-4646.2017.01.005.
[14] ESPINOSA M,ORTEGA R,SANCHEZ M,et al. Association of C4d deposition with clinical outcomes in IgA nephropathy[J]. Clin J Am Soc Nephrol,2014,9(5):897-904. DOI:10.2215/CJN.09710913.
[15] LIU LL,JIANG Y,WANG LN,et al. Urinary mannose-binding lectin is a biomarker for predicting the progression of immunoglobulin (Ig) A nephropathy[J]. Clin Exp Immunol,2012,169(2):148-155. DOI:10.2215/CJN.09710913.
[16] 祝爽爽,李永强,周树露,等. 血清中IgA/C3比值在IgA肾病诊断预测中的价值及其与IgA肾病临床及病理联系[J]. 南方医科大学学报,2015,35(12):1683-1688. DOI:10.3969/j.issn.1673-4254.2015.12.04.
[17] NAKAGAWA H,SUZUKI S,HANEDA M,et al. Significance of glomerular deposition of C3c and C3d in IgA nephropathy[J]. Am J Nephrol,2000,20(2):122-128.
[18] ZHU B,ZHU CF,LIN Y,et al. Clinical characteristics of IgA nephropathy associated with low complement 4 levels[J]. Ren Fail,2015,37(3):424-432. DOI:10.3109/0886022X.2014.994408.
[19] SOGABE A,UTO H,KANMURA S,et al. Correlation of serum levels of complement C4a desArg with pathologically estimated severity of glomerular lesions and mesangial hypercellularity scores in patients with IgA nephropathy[J]. Int J Mol Med,2013,32(2):307-314. DOI:10.3892/ijmm.2013.1390.
[20] ONDA K,OHI H,TAMANO M,et al. Hypercomplementemia in adult patients with IgA nephropathy[J]. J Clin Lab Anal,2007,21(2):77-84. DOI:10.1002/jcla.20154.
[21] ONDA K,OHSAWA I,OHI H,et al. Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function[J]. BMC Nephrol,2011,12:64. DOI:10.1186/1471-2369-12-64.
[22] LIU M,CHEN Y,ZHOU J,et al. Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy[J]. PLoS One,2015,10(6):e126812. DOI:10.1371/journal.pone.0126812.
[23] KIRYLUK K,NOVAK J. The genetics and immunobiology of IgA nephropathy[J]. J Clin Invest,2014,124(6):2325-2332. DOI:10.1172/JCI74475.
[24] GHARAVI AG,KIRYLUK K,CHOI M,et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy[J]. Nat Genet,2011,43(4):321-327. DOI:10.1038/ng.787.
[25] TORTAJADA A,YEBENES H,ABARRATEGUI-GARRIDO C,et al. C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation[J]. J Clin Invest,2013,123(6):2434-2446. DOI:10.1172/JCI68280.
[26] ZHU L,ZHAI YL,WANG FM,et al. Variants in complement factor H and complement factor H-related protein genes,CFHR3 and CFHR1,affect complement activation in IgA nephropathy[J]. J Am Soc Nephrol,2015,26(5):1195-1204. DOI:10.1681/ASN.2014010096.
[27] MEDJERAL-THOMAS NR, LOMAX-BROWNE HJ, BECKWITH H, et al. Circulating complement factor H-related proteins 1 and 5 correlate with disease activity in IgA nephropathy[J]. Kidney Int, 2017, 92(4):942-952. DOI:10.1016/j.kint.2017.03.043.
[28] TORTAJADA A, GUTIERREZ E, GOICOECHEA DE JORGE E, et al. Elevated factor H-related protein 1 and factor H pathogenic variants decrease complement regulation in IgA nephropathy[J]. Kidney Int, 2017, 92(4):953-963. DOI:10.1016/j.kint.2017.03.041.
[1] 刘林林,刘楠,王娟,朱林波,姚丽,徐天华,王力宁. 肾小球C4d 沉积为IgA 肾病的预后因子[J]. 中国医科大学学报, 2017, 46(1): 23-27.
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