Table of Contents Author Guidelines Submit a Manuscript
Clinical and Developmental Immunology
Volume 2011, Article ID 470803, 7 pages
http://dx.doi.org/10.1155/2011/470803
Review Article

Aberrantly Glycosylated IgA1 as a Factor in the Pathogenesis of IgA Nephropathy

1Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
2Department of Pediatrics, Juntendo University School of Medicine, Tokyo 113-8431, Japan
3Molecular Pathology, Biomolecular and Integrated Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki 305-8575, Japan

Received 13 October 2010; Revised 3 December 2010; Accepted 6 January 2011

Academic Editor: Jiri Mestecky

Copyright © 2011 Mototsugu Tanaka et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Berger and N. Hinglais, “Les depots intercapillaires d’IgA-IgG,” Journal d'Urologie et de Nephrology, vol. 74, no. 9, pp. 694–695, 1968 (French). View at Google Scholar
  2. G. D'Amico, “The commonest glomerulonephritis in the world: IgA nephropathy,” Quarterly Journal of Medicine, vol. 64, no. 245, pp. 709–727, 1987. View at Google Scholar · View at Scopus
  3. J. H. Galla, “Iga nephropathy,” Kidney International, vol. 47, no. 2, pp. 377–387, 1995. View at Google Scholar · View at Scopus
  4. G. D'Amico, G. Colasanti, and G. Colasanti, “Long-term follow-up of IgA mesangial nephropathy: clinico-histological study in 374 patients,” Seminars in Nephrology, vol. 7, no. 4, pp. 355–358, 1987. View at Google Scholar · View at Scopus
  5. M. G. Radford, J. V. Donadio, E. J. Bergstralh, and J. P. Grande, “Predicting renal outcome in IgA nephropathy,” Journal of the American Society of Nephrology, vol. 8, no. 2, pp. 199–207, 1997. View at Google Scholar · View at Scopus
  6. L. S. Ibels and A. Z. Gyory, “IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature,” Medicine, vol. 73, no. 2, pp. 79–102, 1994. View at Google Scholar · View at Scopus
  7. R. J. Hogg, F. G. Silva, R. J. Wyatt, J. S. Reisch, J. C. Argyle, and D. A. Savino, “Prognostic indicators in children with IgA nephropathy—report of the Southwest Pediatric Nephrology study group,” Pediatric Nephrology, vol. 8, no. 1, pp. 15–20, 1994. View at Google Scholar · View at Scopus
  8. J. C. Jennette, S. D. Wall, and A. S. Wilkman, “Low incidence of IgA nephropathy in Blacks,” Kidney International, vol. 28, no. 6, pp. 944–950, 1985. View at Google Scholar · View at Scopus
  9. Y. K. Seedat, B. C. Nathoo, K. B. Parag, I. P. Naiker, and R. Ramsaroop, “IgA nephropathy in blacks and Indians of Natal,” Nephron, vol. 50, no. 2, pp. 137–141, 1988. View at Google Scholar · View at Scopus
  10. J. V. Donadio and J. P. Grande, “IgA nephropathy,” New England Journal of Medicine, vol. 347, no. 10, pp. 738–748, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. A. C. Allen, E. M. Bailey, P. E. C. Brenchley, K. S. Buck, J. Barratt, and J. Feehally, “Mesangial Iga1 in IgA nephropathy exhibits aberrant O-glycosylation: observations in three patients,” Kidney International, vol. 60, no. 3, pp. 969–973, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. Y. Hiki, H. Odani, and H. Odani, “Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA nephropathy,” Kidney International, vol. 59, no. 3, pp. 1077–1085, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. J. Novak, M. Tomana, and M. Tomana, “IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells,” Kidney International, vol. 67, no. 2, pp. 504–513, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. I. Narita and F. Gejyo, “Pathogenetic significance of aberrant glycosylation of IgA1 in IgA nephropathy,” Clinical and Experimental Nephrology, vol. 12, no. 5, pp. 332–338, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. A. C. Allen, F. R. Willis, T. J. Beattie, and J. Feehally, “Abnormal IgA glycosylation in Henoch-Schonlein purpura restricted to patients with clinical nephritis,” Nephrology Dialysis Transplantation, vol. 13, no. 4, pp. 930–934, 1998. View at Publisher · View at Google Scholar · View at Scopus
  16. R. J. Levinsky and T. M. Barratt, “IgA immune complexes in Henoch-Schonlein purpura,” Lancet, vol. 2, no. 8152, pp. 1100–1103, 1979. View at Google Scholar · View at Scopus
  17. M. Raska, Z. Moldoveanu, and Z. Moldoveanu, “Identification and characterization of CMP-NeuAc:GalNAc-IgA1 α2,6-sialyltransferase in IgA1-producing cells,” Journal of Molecular Biology, vol. 369, no. 1, pp. 69–78, 2007. View at Publisher · View at Google Scholar · View at PubMed
  18. A. Smith, K. Molyneux, J. Feehally, and J. Barratt, “Is sialylation of IgA the agent provocateur of IgA nephropathy?” Nephrology Dialysis Transplantation, vol. 23, no. 7, pp. 2176–2178, 2008. View at Publisher · View at Google Scholar · View at PubMed
  19. J. H. Galla, “Iga nephropathy,” Kidney International, vol. 47, no. 2, pp. 377–387, 1995. View at Google Scholar
  20. L. Layward, A. C. Allen, J. M. Hattersley, S. J. Harper, and J. Feehally, “Elevation of IgA in IgA nephropathy is localized in the serum and not saliva and is restricted to the IgA1 subclass,” Nephrology Dialysis Transplantation, vol. 8, no. 1, pp. 25–28, 1993. View at Google Scholar
  21. A. H. M. Van Der Helm-Van Mil, A. C. Smith, S. Pouria, E. Tarelli, N. J. Brunskill, and H. C. J. Eikenboom, “Immunoglobulin A multiple myeloma presenting with Henoch-Schönlein purpura associated with reduced sialylation of IgA1,” British Journal of Haematology, vol. 122, no. 6, pp. 915–917, 2003. View at Publisher · View at Google Scholar
  22. A. M. Zickerman, A. C. Allen, and A. C. Allen, “IgA myeloma presenting as Henoch-Schönlein purpura with nephritis,” American Journal of Kidney Diseases, vol. 36, no. 3, p. E19, 2000. View at Google Scholar
  23. H. Iwasaki, Y. Zhang, and Y. Zhang, “Initiation of O-glycan synthesis in IgA1 hinge region is determined by a single enzyme, UDP-N-acetyl-α-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 2,” Journal of Biological Chemistry, vol. 278, no. 8, pp. 5613–5621, 2003. View at Publisher · View at Google Scholar · View at PubMed
  24. T. Ju, K. Brewer, A. D. Souza, R. D. Cummings, and W. M. Canfield, “Cloning and expression of human core 1 β1,3-galactosyltransferase,” Journal of Biological Chemistry, vol. 277, no. 1, pp. 178–186, 2002. View at Publisher · View at Google Scholar · View at PubMed
  25. T. Ju and R. D. Cummings, “A unique molecular chaperone cosmc required for activity of the mammalian core 1 β-galactosyltransferase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 26, pp. 16613–16618, 2002. View at Publisher · View at Google Scholar · View at PubMed
  26. T. Ju and R. D. Cummings, “Protein glycosylation: chaperone mutation in Tn syndrome,” Nature., vol. 437, no. 7063, p. 1252, 2005. View at Google Scholar
  27. H. Suzuki, Z. Moldoveanu, and Z. Moldoveanu, “IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1,” Journal of Clinical Investigation, vol. 118, no. 2, pp. 629–639, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. L. Zhu, W. Tang, and W. Tang, “Interaction between variants of two glycosyltransferase genes in IgA nephropathy,” Kidney International, vol. 76, no. 2, pp. 190–198, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. A. G. Gharavi, Y. Yan, and Y. Yan, “IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23,” Nature Genetics, vol. 26, no. 3, pp. 354–357, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. A. D. Paterson, X. Q. Liu, and X. Q. Liu, “Genome-wide linkage scan of a large family with IgA nephropathy localizes a novel susceptibility locus to chromosome 2q36,” Journal of the American Society of Nephrology, vol. 18, no. 8, pp. 2408–2415, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. A. G. Gharavi, Z. Moldoveanu, and Z. Moldoveanu, “Aberrant IgA1 glycosylation is inherited in familial and sporadic IgA nephropathy,” Journal of the American Society of Nephrology, vol. 19, no. 5, pp. 1008–1014, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. M. Tomana, K. Matousovic, B. A. Julian, J. Radl, K. Konecny, and J. Mestecky, “Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG,” Kidney International, vol. 52, no. 2, pp. 509–516, 1997. View at Google Scholar · View at Scopus
  33. M. Tomana, J. Novak, B. A. Julian, K. Matousovic, K. Konecny, and J. Mestecky, “Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies,” Journal of Clinical Investigation, vol. 104, no. 1, pp. 73–81, 1999. View at Google Scholar · View at Scopus
  34. J. Mestecky, O. H. Hashim, and M. Tomana, “Alterations in the IgA carbohydrate chains influence the cellular distribution of IgA1,” Contributions to nephrology, vol. 111, pp. 66–71, 1995. View at Google Scholar · View at Scopus
  35. C. Ruef, K. Budde, J. Lacy, W. Northemann, M. Baumann, R. B. Sterzel, and D. L. Coleman, “Interleukin 6 is an autocrine growth factor for mesangial cells,” Kidney International, vol. 38, no. 2, pp. 249–257, 1990. View at Google Scholar · View at Scopus
  36. Y. Taniguchi, N. Yorioka, H. Oda, and M. Yamakido, “Platelet-derived growth factor, interleukin (IL)-1β, IL-6, IL-6R and tumor necrosis factor-α in IgA nephropathy. An immunohistochemical study,” Nephron, vol. 74, no. 4, pp. 652–660, 1996. View at Google Scholar · View at Scopus
  37. J. P. Grande, “Role of transforming growth factor-β in tissue injury and repair,” Proceedings of the Society for Experimental Biology and Medicine, vol. 214, no. 1, pp. 27–40, 1997. View at Google Scholar · View at Scopus
  38. K. Yoshioka, T. Takemura, K. Murakami, M. Okada, S. Hino, H. Miyamoto, and S. Maki, “Transforming growth factor-β protein and mRNA in glomeruli in normal and diseased human kidneys,” Laboratory Investigation, vol. 68, no. 2, pp. 154–163, 1993. View at Google Scholar
  39. Y. Taniguchi, N. Yorioka, T. Masaki, Y. Asakimori, K. Yamashita, and M. Yamakido, “Localization of transforming growth factors β1 and β2 and epidermal growth factor in IgA nephropathy,” Scandinavian Journal of Urology and Nephrology, vol. 33, no. 4, pp. 243–247, 1999. View at Publisher · View at Google Scholar · View at Scopus
  40. Z. I. Niemir, H. Stein, I. L. Noronha, C. Kruger, K. Andrassy, E. Ritz, and R. Walherr, “PDGF and TGF-β contribute to the natural course of human IgA glomerulonephritis,” Kidney International, vol. 48, no. 5, pp. 1530–1541, 1995. View at Google Scholar · View at Scopus
  41. H. Suzuki, R. Fan, and R. Fan, “Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity,” Journal of Clinical Investigation, vol. 119, no. 6, pp. 1668–1677, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. Z. Moldoveanu, R. J. Wyatt, and R. J. Wyatt, “Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels,” Kidney International, vol. 71, no. 11, pp. 1148–1154, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. M. C. Hastings, Z. Moldoveanu, and Z. Moldoveanu, “Galactose-deficient IgA1 in African Americans with IgA nephropathy: serum levels and heritability,” Clinical Journal of the American Society of Nephrology, vol. 5, no. 11, pp. 2069–2074, 2010. View at Publisher · View at Google Scholar · View at PubMed
  44. C. Pozzi, P. Bolasco, G. Fogazzi, S. Andrulli, P. Altieri, C. Ponticelli, and F. Locatelli, “Corticosteroids in IgA nephropathy: a randomised controlled trial,” Lancet, vol. 353, no. 9156, pp. 883–887, 1999. View at Publisher · View at Google Scholar · View at Scopus
  45. C. Pozzi, S. Andrulli, and S. Andrulli, “Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial,” Journal of the American Society of Nephrology, vol. 15, no. 1, pp. 157–163, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. M. Praga, E. Gutiérrez, E. González, E. Morales, and E. Hernandez, “Treatment of IgA nephropathy with ace inhibitors: a randomized and controlled trial,” Journal of the American Society of Nephrology, vol. 14, no. 6, pp. 1578–1583, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Manno, D. D. Torres, M. Rossini, F. Pesce, and F. P. Schena, “Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy,” Nephrology Dialysis Transplantation, vol. 24, no. 12, pp. 3694–3701, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. J. Lv, H. Zhang, Y. Chen, G. Li, L. Jiang, A. K. Singh, and H. Wang, “Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial,” American Journal of Kidney Diseases, vol. 53, no. 1, pp. 26–32, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. F. Eitner and J. Floege, “Glomerular disease: ACEIs with or without corticosteroids in IgA nephropathy?” Nature Reviews Nephrology, vol. 6, no. 5, pp. 252–254, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. C. Pozzi, S. Andrulli, and S. Andrulli, “Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy,” Journal of the American Society of Nephrology, vol. 21, no. 10, pp. 1783–1790, 2010. View at Publisher · View at Google Scholar · View at PubMed
  51. S. C. W. Tang, A. W. C. Tang, S. S. H. Wong, J. C. K. Leung, Y. W. Ho, and K. N. Lai, “Long-term study of mycophenolate mofetil treatment in IgA nephropathy,” Kidney International, vol. 77, no. 6, pp. 543–549, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. N. Yoshikawa, H. Ito, and H. Ito, “A controlled trial of combined therapy for newly diagnosed severe childhood IgA nephropathy,” Journal of the American Society of Nephrology, vol. 10, no. 1, pp. 101–109, 1999. View at Google Scholar
  53. N. Yoshikawa, M. Honda, K. Iijima, M. Awazu, S. Hattori, K. Nakanishi, and H. Ito, “Steroid treatment for severe childhood IgA nephropathy: a randomized, controlled trial,” Clinical journal of the American Society of Nephrology, vol. 1, no. 3, pp. 511–517, 2006. View at Publisher · View at Google Scholar · View at PubMed
  54. B. D. Maes, R. Oyen, and R. Oyen, “Mycophenolate mofetil in IgA nephropathy: results of a 3-year prospective placebo-controlled randomized study,” Kidney International, vol. 65, no. 5, pp. 1842–1849, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. G. Frisch, J. Lin, and J. Lin, “Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial,” Nephrology Dialysis Transplantation, vol. 20, no. 10, pp. 2139–2145, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. M. Koselj, T. Rott, A. Kandus, A. Vizjak, and M. Malovrh, “Donor-transmitted IgA nephropathy: long-term follow-up of kidney donors and recipients,” Transplantation Proceedings, vol. 29, no. 8 A, pp. 3406–3407, 1997. View at Publisher · View at Google Scholar · View at Scopus
  57. F. G. Silva, P. Chander, C. L. Pirani, and M. A. Hardy, “Disappearance of glomerular mesangial IgA deposits after renal allograft transplantation.,” Transplantation, vol. 33, no. 2, pp. 241–246, 1982. View at Google Scholar · View at Scopus
  58. J. Novak, H. L. Vu, L. Novak, B. A. Julian, J. Mestecky, and M. Tomana, “Interactions of human mesangial cells with IgA and IgA-containing immune complexes,” Kidney International, vol. 62, no. 2, pp. 465–475, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. I. C. Moura, M. Arcos-Fajardo, and M. Arcos-Fajardo, “Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy,” Journal of the American Society of Nephrology, vol. 15, no. 3, pp. 622–634, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. M. E. Lamm, S. N. Emancipator, J. K. Robinson, M. Yamashita, H. Fujioka, J. Qiu, and A. G. Plaut, “Microbial IgA protease removes IgA immune complexes from mouse glomeruli in vivo: potential therapy for IgA nephropathy,” American Journal of Pathology, vol. 172, no. 1, pp. 31–36, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. M. Tanaka, G. Seki, and G. Seki, “Resolution of Henoch-Schönlein purpura nephritis after acquired IgA deficiency,” Pediatric Nephrology, vol. 25, no. 11, pp. 2355–2358, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. International Study of Kidney Disease in Children, “Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis,” Kidney International, vol. 13, no. 2, pp. 159–165, 1978. View at Google Scholar
  63. K. Schärer, R. Krmar, U. Querfeld, H. Ruder, R. Waldherr, and F. Schaefer, “Clinical outcome of Schonlein-Henoch purpura nephritis in children,” Pediatric Nephrology, vol. 13, no. 9, pp. 816–823, 1999. View at Publisher · View at Google Scholar · View at Scopus