Skip to main content
SpringerLink
Log in

Complement and glomerulonephritis — an update

  • Invited Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The complement (C) system in man and its relationship to disease has been the subject of intensive research. In this review, we update the information concerning the nature of the various C components, and present some of the similarities between structure and function of the C components and their respective genes. The clinical problems which are encountered in individuals with acquired C abnormalities and with a genetically determined deficiency of a single component provide helpful clues to understanding the affected patients and the possible functional importance of the particular deficient component. The steady progress in identifying both normal variants of C components and the gene defects which produce C deficiencies offers the prospect of correlating structure of the C components with possible pathogenic roles in disease. Genetically determined C abnormalities are more commonly recognized during childhood. An appreciation of the basic aspects of the C system is a helpful tool for the pediatric nephrologist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Müller-Eberhard HJ (1988) Molecular organization and function of the complement system. Annu Rev Biochem 57: 321–347

    Google Scholar 

  2. Campbell RD, Alex Law SK (1988) Structure, organization, and regulation of the complement genes. Annu Rev Immunol 6: 161–195

    Google Scholar 

  3. Erdei A, Fust G, Gergely J (1991) The role of C3 in the immune response. Immunol Today 12: 332–337

    Google Scholar 

  4. Finco O, Li S, Cuccia M, Rosen FS, Carroll MC (1992) Structural differences between the two human complement C4 isotypes affect the humoral immune response. J Exp Med 175: 537–543

    Google Scholar 

  5. Ross SC, Densen P (1984) Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in immune deficiency. Medicine (Baltimore) 63: 243–273

    Google Scholar 

  6. Figueroa JE, Densen P (1991) Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 4: 359–395

    Google Scholar 

  7. Morgan BP, Walport MJ (1991) Complement deficiency and disease. Immunol Today 12: 301–306

    Google Scholar 

  8. Kinoshita T (1991) Biology of complement: the overture. Immunol Today 12: 291–295

    Google Scholar 

  9. Law SKA, Dodds AW, Porter RR (1984) A comparison of the properties of the two classes. C4A and C4B, of the human complement component C4. EMBO J 3: 1819–1823

    Google Scholar 

  10. Isenman DE, Young JR (1984) The molecular basis for the difference in immune hemolysis activity of the Chido and Rodgers isotype of human complement component C4. J Immunol 132: 3019–3027

    Google Scholar 

  11. Jahn I, Uring-Lambert B, Arnold D, Clemenceau S, Hauptmann G (1990) C2 referece typing report. Complement Inflamm 7: 175–182

    Google Scholar 

  12. Rittner C, Stradmann-Bellinghausen B (1990) C3 reference typing report and nomenclature revision. Complement Inflamm 7: 230–233

    Google Scholar 

  13. Mauff G, Brenden M, Braun-Stilwell M, Doxiadia G, Giles CM, Hauptmann G, Rittner C, Schneider PM, Stradmann-Bellinghausen B, Uring-Lambert B (1990) C4 reference typing reports. Complement Inflamm 7: 193–212

    Google Scholar 

  14. Hobart MH, vazGuedes MA, Lachmann PJ (1981) Polymorphism of human C5. Ann Hum Genet 45: 1–4

    Google Scholar 

  15. Tokunaga K, Jin F, Mauff G, Nishimukai H, Simeoni E, Suzuki K, Weber W (1990) Co reference typing report. Complement Inflamm 7: 234–239

    Google Scholar 

  16. Hobart MJ (1990) C7 reference typing and nomenclature recommendations1. Complement Inflamm 7: 240–242

    Google Scholar 

  17. Rogde S, Mevag B, Teisberg P, Gedde-Dahl T Jr, Tedesco F, Olaisen B (1985) Genetic polymorphism of complement component C8. Hum Genet 70: 211–216

    Google Scholar 

  18. Alper CA, Marcus D, Raum D, Petersen BH, Spira TJ (1983) Genetic polymorphism in C8β-chain: evidence for two unlinked genetic loci for the eighth component of human complement. J Clin Invest 72: 1526–1531

    Google Scholar 

  19. Nakmura S, Nishimukai H, Sawaguchi A, Zhou M (1990) Factor I reference typing report. Complement Inflamm 7: 248–251

    Google Scholar 

  20. Geserick G, Abbal M, Brenden M, Braun-Stilwell M, Mauff G, Schroder H, Siemens I (1990) Factor B reference typing report. Complement Inflamm 7: 183–189

    Google Scholar 

  21. Rogde S, Mevag B, Olaisen B, Geede-Dahl T Jr, Teisberg P (1984) Structural genes for complement factor C8 (C8) on chromosome 1 (abstract). Cytogenet Cell Genet 37: 571

    Google Scholar 

  22. Rittner C, Hargesheimer W, Mollenhauer E (1984) Population and formal genetics of the human C81 (alpha-gamma) polymorphism. Hum Genet 67: 166–169

    Google Scholar 

  23. Kaufman KM, Snider JV, Spurr NK, Schwartz CE, Sodetz JM (1989) Chromosomal assignment of genes encoding the alpha, beta and gamma subunits of human complement protein C8. Identification of a close physical linkage between the alpha and beta loci. Genomics 5: 475–480

    Google Scholar 

  24. Porter RR (1983) Complement polymorphism, the major histocompatibility complex and associated disease: a speculation. Med Biol 1: 161–168

    Google Scholar 

  25. Wurzner R, Orren A, Lachmann PJ (1992) Inherited deficiencies of the terminal components of human complement. Immunodetic Rev 3: 123–147

    Google Scholar 

  26. McLean RH, Wyatt RJ, Julian BA (1984) Complement phenotypes in glomerulonephritis: increased frequency of homozygous null C4 phenotypes in IgA nephropathy and Henoch-Schönlein purpura. Kidney Int 26: 855–860

    Google Scholar 

  27. Ault BH, Stapleton FB, Rivas ML, Waldo FB, Roy S III, McLean RH, Bin J, Wyatt RJ (1990) Association of Henoch-Schönlein purpura glomerulonephritis with C4B deficiency. J Pediatr 117: 753–755

    Google Scholar 

  28. Wyatt RJ, Julian BA, Woodford SY, Wang C, Roberts J, Thompson JS, Christenson MJ, McLean RH (1991) C4A deficiency and poor prognosis in patients with IgA nephropathy. Clin Nephrol 36: 1–5

    Google Scholar 

  29. Welch TR, Beischerl L, Balakrishnan K, et al (1986) Major histocompatibility-complex extended haplotypes in membranoproliferative glomerulonephritis. N Engl J Med 314: 1476–1481

    Google Scholar 

  30. Rowe PC, McLean RH, Wood RA, Leggiadro RJ, Winkelstein JA (1989) Association of homozygous C4B deficiency with bacterial meningitis. J Infect Dis 160: 448–451

    Google Scholar 

  31. Bishof NA, Welch TR, Beischel LS (1990) C4B deficiency: a risk factor for bactermia with encapsulated organisms. J Infect Dis 162: 248–250

    Google Scholar 

  32. Cates KL, Densen P, Lockman JC, Levine RP (1992) C4B deticiency is not associated with meningitis or bacteremia with encapsulated bacteria. J Infect Dis 165: 942–944

    Google Scholar 

  33. Dawkins RL, Christenson FT, Kay PH, Garlepp MJ, McCluskey J, Hollingsworth PH, Zilko PJ (1983) Disease associations with complotypes, supratypes and haplotypes. Immunol Rev 70: 5–22

    Google Scholar 

  34. Batchelor JR, McMichael AJ (1987) Progress in understanding HLA and disease associations. Br Med Bull 43: 156–183

    Google Scholar 

  35. Howard PF, Hochberg MC, Bias WB, et al (1986) Relationship between C null genes. HLA-D region antigens and genetic susceptibility to systemic lupus erythematosus in Caucasian and Black Americans. Am J Med 81: 187–193

    Google Scholar 

  36. Fielder AHL, Walport MJ, Batchelor JR, et al (1983) Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility. BMJ 286: 425–428

    Google Scholar 

  37. Hauptmann G, Trappeiner G, Schifferli JA (1988) Inherited deficiency of the fourth component of human complement. Immunodefic Rev 1: 3–22

    Google Scholar 

  38. Batchelor JR, Fielder AH, Walport MJ (1987) Family study of the major histocompatibility complex in HLA DR3 negative patients with systemic lupus erythematosus. Clin Exp Immunol 70: 364–371

    Google Scholar 

  39. Schifferli JA, Ng YC, Peters DK (1986) The role of complement and its receptor in the elimination of immune complexes. N Engl J Med 315: 488–495

    Google Scholar 

  40. Thompson RA, Winterborn MH (1981) Hypocomplementaemia due to a genetic deficiency of BH globulin. Clin Exp Immunol 467: 110–119

    Google Scholar 

  41. Wyatt RJ, Julian BA, Weinstein A, Rothfield NF, McLean RH (1982) Partial H (β1H) deficiency and glomerulonephritis in two families. J Clin Immunol 2: 110–117

    Google Scholar 

  42. Frank MM (1987) Complement in the pathophysiology of human disease. N Engl J Med 316: 1525–1530

    Google Scholar 

  43. West CD, Northway JD, Davis NC (1964) Serum levels of beta-1-C globulin, a complement component, in the nephritides, lipoid nephrosis and other conditions. J Clin Invest 43: 1507–1517

    Google Scholar 

  44. Gewerz H, Pickering RJ, Mergenhagen SE, Good RA (1968) The complement profile in acute glomerulonephritis, systemic lupus erythematosus and hypocomplementemic chromic glomerulonephritis. Int Arch Allergy Appl Immunol 34: 556

    Google Scholar 

  45. Schur PH, Sandsen J (1968) Immunologic factors and clinical activity in systemic lupus erythematosus. N Engl J Med 278: 533

    Google Scholar 

  46. Kohler PF, Bensel R ten (1969) Serial complement component alterations in acute glomerulonephritis and systemic lupus erythematosus. Clin Exp Immunol 4: 191

    Google Scholar 

  47. McLean RH, Michael AF (1973) Alternate pathway components properdin and C3 proactivator in human glomerulonephritis. J Clin Invest 52: 634

    Google Scholar 

  48. Pickering RJ, Michael AF, Herdman RJ, Good RA, Gewurz H (1971) The complement system in chronic glomerulonephritis: three newly associated aberrations. J Pediatr 78: 30–43

    Google Scholar 

  49. Cork LC, Morris JM, Olson JL, Krakowka S, Swift AJ, Winkelstein JA (1991) Membranoproliferative glomerulonephritis in dogs with a genetically determined deficiency of the third component of complement. Clin Immunol Immunopathol 60: 455–470

    Google Scholar 

  50. Couser WG, Ochi RF, Baker PJ, Schulze M, Campbell C, Johnson RJ (1991) Co depletion reduces proteinuria in experimental nephropathy induced by a nonglomerular antigen. J Am Soc Nephrol 2: 894–901

    Google Scholar 

  51. Paul L, Skanes VM, Mayden J, Levine RP (1988) C4-mediated inhibition of immune precipitation and differences in inhibitory action of genetic variants, C4A3 and C4B1. Complement 5: 110–119

    Google Scholar 

  52. Lagueruela CC, Buettner TL, Cole BR, Kissan JM, Robson AM (1990) HLA extended haplotypes in steroid-sensitive nephrotic syndrome of childhood. Kidney Int 38: 145–150

    Google Scholar 

  53. Ricker DM, Hebert LA, Rohde R, Sedmak DD, Lewis EJ, Clough JD and The Lupus Nephritis Collaborative Study Group (1991) Serum C3 levels are diagnostically more sensitive and specific for systemic lupus erythematosus activity than are serum C4 levels. Am J Kidney Dis 18: 678–685

    Google Scholar 

  54. Nitsche JF, Tucker SE III, Sugimoto S (1981) Rocket immunoelectrophoresis of C4 and C4d. A simple sensitive method for detecting complement activation in plasma. Am J Clin Pathol 76: 679–684

    Google Scholar 

  55. Wyatt RJ, Forristal J, West CD, et al (1988) Complement profiles in acute post-streptococcal glomerulonephritis. Pediatr Nephrol 2: 219–223

    Google Scholar 

  56. Strife CF, McDonald BM, Ruley EJ, et al (1976) Shunt nephritis: the nature of the serum cryoglobulins and their relation to the complement profile. J Pediatr 88: 403–413

    Google Scholar 

  57. Varade WS, Forristal J, West CD (1990) Patterns of complement activation in idiopathic membranoproliferative glomerulonephritis types I, II, and III. Am J Kidney Dis 16: 196–206

    Google Scholar 

  58. Coleman TH, Forristal J, Kosaka T, et al (1983) Inherited complement component deficiencies in membranoproliferative glomerulonephritis. Kidney Int 24: 681–690

    Google Scholar 

  59. Matsell DG, Roy III S, Tamerius JD, Morrow PR, Kolb WP, Wyatt RJ (1991) Plasma terminal complement complexes in acute poststreptococcal glomerulonephritis. Am J Kidney Dis 17: 311–316

    Google Scholar 

  60. Michael AF, McLean RH, Roy LP, Westberg NG, Hoyer JR, Fish AJ, Vernier RL (1973) Immunologic aspects of the nephrotic syndrome. Kidney Int 3: 105–115

    Google Scholar 

  61. Wyatt RJ, Jones D, Stapleton FB, Roy S III, Odom TW, McLean RH (1985) Recurrent hemolytic uremic syndrome with the hypomorphic fast allele of the third component of complement. J Pediatr 107: 564–565

    Google Scholar 

  62. Bogdanovic R, Cvoric A, Nikolic V, Sindjic M (1988) Recurrent haemolytic uraemic syndrome with hypocomplementaemiana case report. Pediatr Nephrol 2: 236–238

    Google Scholar 

  63. Roodhooft AM, McLean RH, Elst E, Van Acker KJ (1990) Recurrent haemolytic uraemic syndrome and acquired hypomorphic variant of the third component of complement. Pediatr Nephrol 4: 597–599

    Google Scholar 

  64. Orren A, Potter PC, Cooper RC, Toit E du (1987) Deficiency of the sixth component of complement and susceptibility toNeisseria meningitidis infections: studies in 10 families and five isonared cases. Immunology 62: 249–253

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Nephrology, Johns Hopkins University, School of Medicine, Baltimore, USA

    Robert H. McLean

Authors
  1. Robert H. McLean
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

McLean, R.H. Complement and glomerulonephritis — an update. Pediatr Nephrol 7, 226–232 (1993). https://doi.org/10.1007/BF00864413

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00864413

Key words

Search

Navigation