Clinical relevance of membrane attack complex deposition in children with IgA nephropathy and Henoch-Schönlein purpura



IgA nephropathy (IgAN) and Henoch-Schönlein purpura are common glomerular disorders in children sharing the same histopathologic pattern of IgA deposits within the mesangium, even if their physiopathology may be different. Repeated exposure to pathogens induces the production of abnormal IgA1. The immune complex deposition in the renal mesangium in IgAN or potentially in small vessels in Henoch-Schönlein purpura induces complement activation via the alternative and lectin pathways. Recent studies suggest that levels of membrane attack complex (MAC) in the urine might be a useful indicator of renal injury. Because of the emerging availability of therapies that selectively block complement activation, the aim of the present study is to investigate whether MAC immunostaining might be a useful marker of IgA-mediated renal injury.


We conducted immunohistochemistry analysis of the MAC on renal biopsies from 67 pediatric patients with IgAN and Henoch-Schönlein purpura. We classified their renal biopsies according to the Oxford classification, retrieved symptoms, biological parameters, treatment, and follow-up.


We found MAC expression was significantly related to impaired renal function and patients whose clinical course required therapy. MAC deposits tend to be more abundant in patients with decreased glomerular filtration rate (p = 0.02), patients with proteinuria > 0.750 g/day/1.73 m2, and with nephrotic syndrome. No correlation with histological alterations was observed.


We conclude that MAC deposition could be a useful additional indicator of renal injury in patients with IgAN and Henoch-Schönlein purpura, independent of other indicators.

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  1. 1.

    Berger J, Hinglais N (1968) Intercapillary deposits of IgA-IgG. J Urol Nephrol 74:694–695

  2. 2.

    Barratt J, Feehally J (2005) IgA nephropathy. J Am Soc Nephrol 16:2088–2097

  3. 3.

    Wyatt RJ, Julian BA (2013) IgA nephropathy. N Engl J Med 368:2402–2414

  4. 4.

    Roos A, Rastaldi MP, Calvaresi N, Oortwijn BD, Schlagwein N, van Gijlswijk-Janssen DJ, Stahl GL, Matsushita M, Fujita T, van Kooten C, Daha MR (2006) Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol 17:1724–1734

  5. 5.

    Hisano S, Matsushita M, Fujita T, Iwasaki H (2005) Activation of the lectin complement pathway in Henoch-Schönlein purpura nephritis. Am J Kidney Dis 45:295–302

  6. 6.

    Medjeral-Thomas NR, Lomax-Browne HJ, Beckwith H, Willicombe M, McLean AG, Brookes P, Pusey CD, Falchi M, Cook HT, Pickering MC (2017) Circulating complement factor H-related proteins 1 and 5 correlate with disease activity in IgA nephropathy. Kidney Int 92:942–952

  7. 7.

    Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, Van Egmond M (2017) New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura). Autoimmun Rev 16:1246–1253

  8. 8.

    Onda K, Ohsawa I, Ohi H, Tamano M, Mano S, Wakabayashi M, Toki A, Horikoshi S, Fujita T, Tomino Y (2011) Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function. BMC Nephrol 12:64–72

  9. 9.

    Rosenblad T, Rebetz J, Johansson M, Békássy Z, Sartz L, Karpman D (2014) Eculizumab treatment for rescue of renal function in IgA nephropathy. Pediatr Nephrol 29:2225–2228

  10. 10.

    Herzog AL, Wanner C, Amann K, Lopau K (2017) First treatment of relapsing rapidly progressive IgA nephropathy with eculizumab after living kidney donation: a case report. Transplant Proc 49:1574–1577

  11. 11.

    Rizk DV, Maillard N, Julian BA, Knoppova B, Green TJ, Novak J, Wyatt RJ (2019) The emerging role of complement proteins as a target for therapy of IgA nephropathy. Front Immunol 10:504

  12. 12.

    Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin N Am 34:571–590

  13. 13.

    Radhakrishnan J, Cattran DC (2012) The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. Kidney Int :840–856

  14. 14.

    Hisano S, Joh K, Katafuchi R, Shimizu A, Hashiguchi N, Kawamura T, Matsuo S, IgA Nephropathy Study Group in Japan (2017) Reproducibility for pathological prognostics parameters of the Oxford classification of IgA nephropathy : a Japanese cohort study of the ministry of health, labor and welfare. Clin Exp Nephrol 21:92–96

  15. 15.

    Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, Cattran DC, Coppo R, D’Agati V, D’Amico G, Emancipator S, Emma F, Feehally J, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H (2009) The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int 76:546–556

  16. 16.

    Le W, Zeng CH, Liu Z, Liu D, Yang Q, Lin RX, Xia ZK, Fan ZM, Zhu G, Wu Y, Xu H, Zhai Y, Ding Y, Yang X, Liang S, Chen H, Xu F, Huang Q, Shen H, Wang J, Fogo AB, Liu ZH (2012) Validation of the Oxford classification of IgA nephropathy for pediatric patients from China. BMC Nephrol 13:158–164

  17. 17.

    Lv J, Shi S, Xu D, Zhang H, Troyanov S, Cattran DC, Wang H (2013) Evaluation of the Oxford classification of IgA nephropathy: a systematic review and meta-analysis. Am J Kidney Dis 62:891–899

  18. 18.

    Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Hashimura Y, Kaito H, Sako M, Iijima K, Yoshikawa N (2012) Validity of the Oxford classification of IgA nephropathy in children. Pediatr Nephrol 27:783–792

  19. 19.

    Coppo R, Lofaro D, Camilla RR, Bellur S, Cattran D, Cook HT, Roberts IS, Peruzzi L, Amore A, Emma F, Fuiano L, Berg U, Topaloglu R, Bilginer Y, Gesualdo L, Polci R, Mizerska-Wasiak M, Caliskan Y, Lundberg S, Cancarini G, Geddes C, Wetzels J, Wiecek A, Durlik M, Cusinato S, Rollino C, Maggio M, Praga M, Smerud HK, Tesar V, Maixnerova D, Barratt J, Papalia T, Bonofiglio R, Mazzucco G, Giannakakis C, Soderberg M, Orhan D, Di Palma AM, Maldyk J, Ozluk Y, Sudelin B, Tardanico R, Kipgen D, Steenbergen E, Karkoszka H, Perkowska-Ptasinska A, Ferrario F, Gutierrez E, Honsova E (2017) Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort. Pediatr Nephrol 32:193–194

  20. 20.

    Haas M, Verhave JC, Liu ZH, Liu ZH, Alpers CE, Barratt J, Becker JU, Cattran D, Cook HT, Coppo R, Feehally J, Pani A, Perkowska-Ptasinska A, Roberts IS, Soares MF, Trimarchi H, Wang S, Yuzawa Y, Zhang H, Troyanov S, Katafuchi R (2017) A multicenter study of the predictive value of crescents in IgA nephropathy. J Am Soc Nephrol 28:691–701

  21. 21.

    Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Coppo R, Troyanov S, Camilla R, Hogg RJ, Cattran DC, Cook HT, Feehally J, Roberts IS, Amore A, Alpers CE, Barratt J, Berthoux F, Bonsib S, Bruijn JA, D’ Agati V, D’ Amico G, Emancipator SN, Emma F, Ferrario F, Fervenza FC, Florquin S, Fogo AB, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H (2010) The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int 77:921–927

  22. 22.

    Edström Halling S, Söderberg MP, Berg UB (2012) Predictors of outcome in paediatric IgA nephropathy with regard to clinical and histopathological variables (Oxford classification). Nephrol Dial Transplant 27:715–722

  23. 23.

    Xu K, Zhang L, Ding J, Wang S, Su B, Xiao H, Wang F, Zhong X, Li Y (2018) Value of the Oxford classification of IgA nephropathy in children with Henoch-Schönlein purpura nephritis. J Nephrol 31:279–286

  24. 24.

    Rauterberg EW, Lieberknecht HM, Wingen AM, Ritz E (1987) Complement membrane attack (MAC) in idiopathic IgA-glomerulonephritis. Kidney Int 31:820–829

  25. 25.

    Miyamoto H, Yoshioka K, Takemura T, Akano N, Maki S (1988) Immunohistochemical study of the membrane attack complex of complement in IgA nephropathy. Virchows Arch A Pathol Anat Histopathol 413:77–86

  26. 26.

    Podack ER, Müller-Eberhard HJ (1980) SC5b-9 complex of complement: formation of the dimeric membrane attack complex by removal of S-protein. J Immunol 124:1779–1783

  27. 27.

    Bhakdi S, Tranum-Jensen J, Klump O (1980) The terminal membrane C5b-9 complex of human complement. Evidence for the existence of multiple protease-resistant polypeptides that form the trans-membrane complement channel. J Immunol 124:2451–2457

  28. 28.

    Eguchi K, Tomino Y, Yagame M, Miyazaki M, Takiura F, Miura M, Suga T, Endoh M, Nomoto Y, Sakai H (1987) Double immunofluorescence studies of IgA and poly C9 (MAC) in glomeruli from patients with IgA nephropathy. Tokai J Exp Clin Med 12:331–335

  29. 29.

    Koskela M, Ylinen E, Ukonmaanaho EM, Autio-Harmainen H, Heikkilä P, Lohi J, Jauhola O, Ronkainen J, Jahnukainen T, Nuutinen M (2017) The ISKDC classification and a new semiquantitative classification for predicting outcomes of Henoch-Schonlein purpura nephritis. Pediatr Nephrol 32:1201–1209

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The authors thank Dr. Luc Laurier Oligny for his constructive criticisms.

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Correspondence to Natalie Patey.

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Dumont, C., Mérouani, A., Ducruet, T. et al. Clinical relevance of membrane attack complex deposition in children with IgA nephropathy and Henoch-Schönlein purpura. Pediatr Nephrol (2020).

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  • Membrane attack complex
  • IgA nephropathy
  • Henoch-Schönlein purpura
  • Pediatric