Skip to main content
NCBI home page
Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2007 Mar 26;21(2):77–84. doi: 10.1002/jcla.20154

Hypercomplementemia in adult patients with IgA nephropathy

Kisara Onda 1, Hiroyuki Ohi 1, Mariko Tamano 1, Isao Ohsawa 1, Michiro Wakabayashi 1, Satoshi Horikoshi 1, Teizo Fujita 2, Yasuhiko Tomino 1,✉
PMCID: PMC6649110  PMID: 17385664

Abstract

IgA nephropathy (IgAN) is the most common form of chronic glomerulonephritis. Although glomerular deposition of complement components is well known, the evidence of serological complement activation in IgAN is inconclusive. We hypothesized that serum levels of complement components and regulatory proteins in patients with IgAN are correlated with its pathogenesis. In the present study we measured complement components in 50 patients with IgAN and 50 healthy volunteers. C5, C1 inhibitor, factor B, C4 binding protein, factor H, and factor I were measured with the use of single radial immunodiffusion. Mannose‐binding lectin (MBL) and properdin (P) were measured by enzyme‐linked immunosorbent assay (ELISA). The correlations among complements in the sera of patients with clinical gradings for IgAN (i.e., the good prognosis group, relatively good prognosis group, relatively poor prognosis group, and poor prognosis group) were evaluated. CH50, C4, factor B, P, factor I, and factor H were significantly higher in IgAN patients than in healthy controls. There were significant correlations between C5 and C4 binding protein, between C3 and C5, or between C4 and factor B in patients with IgAN. In the poor prognosis group, C4 binding protein was significantly higher than in the other groups of IgAN patients. hypercomplementemia occurs in IgAN and is associated with an increase in complement regulatory protein (CRP). C4 binding protein analyses can be used to predict disease prognosis. J. Clin. Lab. Anal. 21:77–84, 2007. © 2007 Wiley‐Liss, Inc.

Keywords: complement, complement regulatory protein, IgA nephropathy, C4 binding protein, factor H

REFERENCES

  • 1. Shirai T, Tomino Y, Sato M, Yoshiki T, Itoh T. IgA nephropathy: clinicopathology and immunopathology. Contrib Nephrol 1978;9:88. [DOI] [PubMed] [Google Scholar]
  • 2. Burkholder PM, Zimmermans SW, Moorthy AV. A clinicopathologic study of natural history of mesangial IgA nephropathy In: Japan Medical Research Foundation, editor. Glomerulonephritis. Tokyo: University of Tokyo Press; 1979. p 143. [Google Scholar]
  • 3. Sakai O, Kitajima T, Kawamura K, Ueda Y. Clinicopathological studies on IgA glomerulonephritis In: Glomerulonephritis. Tokyo: University of Tokyo Press; 1979. p 167. [Google Scholar]
  • 4. Endo M, Ohi H, Ohsawa I, Fujita T, Matsushita M, Fujita T. Glomerular deposition of mannose‐binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy. Nephrol Dial Transplant 1998;13:1984–1990. [DOI] [PubMed] [Google Scholar]
  • 5. Endo M, Ohi H, Satomura A, Hidaka M, Ohsawa I, Fujita T, Kanmatsuse K, Matsushita M, Fujita T. Regulation of in situ complement activation via the lectin pathway in patients with IgA nephropathy. Clin Nephrol 2001;3:55:185–191. [PubMed] [Google Scholar]
  • 6. Matsuda M, Shikata K, Wada J, Sugimoto H, Shikata Y, Kawasaki T, Makino H. Deposition of mannan binding protein and mannan binding protein‐mediated complement activation in the glomeruli of patients with IgA nephropathy. Nephron 1998;80:408–413. [DOI] [PubMed] [Google Scholar]
  • 7. Gotze O, Muller‐Eberbard H.J. The C3‐activation system: an alternative pathway of complement activation. J Exp Med 1971;1:134:90S–108S. [PubMed] [Google Scholar]
  • 8. Russell MW, Kilian M, Lamm ME. Biological activity of IgA In: Ogra PL, Hestecky J, Lamm ME, Strober W, Bienenstock J, McGhee JR, editors. Mucosal immunology. San Diego: Academic Press; 1999. p 225. [Google Scholar]
  • 9. Hiemstra PS, Biewenga J, Gorter A, et al. Activation of complement by human serum IgA, secretory IgA and IgA1 fragments. Mol Immunol 1988;25:527–533. [DOI] [PubMed] [Google Scholar]
  • 10. Janoff EN, Fasching C, Orenstein JM, Rubins JB, Opstad NL, Dalmasso AP. Killing of Streptococcus pneumoniae by capsular polysaccharide‐specific polymeric IgA, complement, and phagocytes. J Clin Invest 1999;104:1139–1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Schaapherder AF, Gooszen HG, teBulte MT, Daha MR. Human complement activation via the alternative pathway on porcine endothelium initiated by IgA antibodies. Transplantation 1995;60:287–291. [DOI] [PubMed] [Google Scholar]
  • 12. Roos A, Bouwman LH, Gulswijk‐Janssen DJ, Faber‐Krol MC, Stahl GL, Daha MR. Human IgA activates the complement system via the mannan‐binding lectin pathway. J Immunol 2001;167:2861–2868. [DOI] [PubMed] [Google Scholar]
  • 13. d'Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med 1987;64:709–727. [PubMed] [Google Scholar]
  • 14. Johnston PA, Brown JS, Braumholtz DA, Davison AM. Clinicopathological correlations and long‐term follow‐up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulonephritis Registry. Q J Med 1992;84:619–627. [PubMed] [Google Scholar]
  • 15. van der Boog PJ, De Fijter JW, Bruijn JA, Van Es LA. Recurrence of IgA nephropathy after renal transplantation. Ann Med Intern (Paris) 1999;150:137–142. [PubMed] [Google Scholar]
  • 16. Baenziger J, Kornfeld S. Structure of the carbohydrate units of IgA1 immunoglobulin. II. Structure of the O‐glycosidically linked oligosaccharide units. J Biol Chem 1974;249:7270–7281. [PubMed] [Google Scholar]
  • 17. Mattu TS, Pleass RJ, Willis AC, et al. The glycosylation and structure of human serum IgA1, Fab, and Fc regions and the role of N‐glycosylation on Fc alpha receptor interactions. J Biol Chem 1998;273:2260–2272. [DOI] [PubMed] [Google Scholar]
  • 18. Andre PM, Le Pogamp P, Chevet D. Impairment of jacalin binding to serum IgA in IgA nephropathy. J Clin Lab Anal 1990;4:115–119. [DOI] [PubMed] [Google Scholar]
  • 19. Allen AC, Harper SJ, Feehally J. Galactosylation of N‐linked and O‐linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy. Clin Exp Immunol 1995;100:470–474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Hiki Y, Iwase H, Saitoh M, et al. Reactivity of glomerular and serum IgA1 to jacalin in IgA nephropathy. Nephron 1996;72:429–435. [DOI] [PubMed] [Google Scholar]
  • 21. Tomana M, Matousovic K, Julian BA, Radl J, Konecny K, Mestecky J. Galactose‐deficient IgA1 in sera of IgA nephropathy patients is present in complex with IgG. Kidney Int 1997;52:509–516. [DOI] [PubMed] [Google Scholar]
  • 22. Kokubo T, Hiki Y, Iwase H, et al. Protective role of IgA1 glycans against IgA1 self aggregation and adhesion to extracellular matrix proteins. J Am Soc Nephrol 1998;9:2048–2054. [DOI] [PubMed] [Google Scholar]
  • 23. Tomana M, Novak J, Julian BA, Matousovic K, Konechy K, Mestecky J. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose‐deficient hinge region and antiglycan antibodies. J Clin Invest 1999;104:73–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Egido J, Sancho J, Rivera F, Hernando L. The role of IgA and IgG immune complexes in IgA nephropathy. Nephron 1984;36:52–59. [DOI] [PubMed] [Google Scholar]
  • 25. Delacroix DL, Elkom KB, Geubel AP, Hodgson HF, Dive C, Vaerman JP. Changes in size, subclass, and metabolic properties of serum immunoglobulin A in liver disease and in other diseases with high serum immunoglobulin A. J Clin Invest 1983;71:358–367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Peterman JH, Julian BA, Kirk KA, Jackson S. Selective elevation of monomeric IgA1 in IgA nephropathy patients with normal renal function. Am J Kidney Dis 1991;18:313–319. [DOI] [PubMed] [Google Scholar]
  • 27. van den Wall Bake AW, Daha MR, van der Ark A, Hiemstra PS, Radl J, van Es LA. Serum levels and in vitro production of IgA subclasses in patients with primary IgA nephropathy. Clin Exp Immunol 1988;74:115–120. [PMC free article] [PubMed] [Google Scholar]
  • 28. Coppo R, Basolo B, Martina G, et al. Circulating immune complexes containing IgA, IgG and IgM in patients with primary IgA nephropathy and with Henoch‐Schonlein nephritis. Correlation with clinical and histologic signs of activity. Clin Nephrol 1982;18:230–239. [PubMed] [Google Scholar]
  • 29. Czerkinsky C, Koopman WJ, Jackson S, et al. Circulating immune complexes and immunoglobulin A rheumatoid factor in patients with mesangial immunoglobulin A nephropathies. J Clin Invest 1986;77:1931–1938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Schena FP, Pastore A, Ludovico N, Sinico RA, Benuzzi S, Montinaro V. Increased serum levels of IgA1‐IgG immune complexes and anti‐F (ab′) 2 antibodies in patients with primary IgA nephropathy. Clin Exp Immnol 1989;77:15–20. [PMC free article] [PubMed] [Google Scholar]
  • 31. Kanatsu K, Doi T, Sekita K, Yoshida H, Nagai H, Hamashima Y. A comparative immunologic study of IgA nephropathy. Am J Kidney Dis 1983;2:618–625. [DOI] [PubMed] [Google Scholar]
  • 32. Tomino Y, Sakai H. Clinical guidelines for immunoglobulin A (IgA) nephropathy in Japan, second version. Clinical and Experimental Nephrology 2003;7:93–97. [DOI] [PubMed] [Google Scholar]
  • 33. Dubaniewicz A, Sztaba‐Kania M, Hoppe A. Analysis of some immunological parameters in pulmonary tuberculosis. Pol Merkuriusz Lek 2004;16:123–127. [PubMed] [Google Scholar]
  • 34. Lachmann PJ, Hughes‐Jones NC. Initiation of complement activation. Springer Semin Immunopathol 1984;7:143–162. [DOI] [PubMed] [Google Scholar]
  • 35. Pangburn MK, Muller‐Eberhard HJ. Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement. J Exp Med 1980;152:1102–1114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Pangburn MK, Morrison DC, Schreiber RD, Muller‐Eberhard HJ. Activation of the alternative complement pathway: recognition of surface structures on activators by bound C3b. J Immunol 1980;124:977–982. [PubMed] [Google Scholar]
  • 37. Mak LW, Lachmann PJ, Majewski J. The activation of the C3b feedback cycle with human complement components. I. Through the classical pathway. Clin Exp Immunol 1977;30:200–210. [PMC free article] [PubMed] [Google Scholar]
  • 38. Miyazaki R, Kuroda M, Akiyama T, Otani I, Tofuku Y, Takeda R. Glomerular deposition and serum levels of complement control proteins in patients with IgA nephropathy. Clin Nephrol 1984;21:335–340. [PubMed] [Google Scholar]
  • 39. Sagripanti A, Cozza V, Baicchi U, Camici M, Cupisti A, Barsotti G. Increased thrombin generation in patients with chronic renal failure. Int J Clin Lab Res 1997;27:72–75. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Laboratory Analysis are provided here courtesy of Wiley

RESOURCES