Abstracts
Résumé
La néphropathie à immunoglobulines A (IgA) ou maladie de Berger est la plus fréquente des glomérulonéphrites primitives et une des premières causes d’insuffisance rénale terminale. Elle se caractérise par des dépôts mésangiaux de complexes d’IgA1 polymériques. Alors que l’épidémiologie et l’évolution clinique sont bien établies, les causes et mécanismes de cette affection restent inconnus. Les études biochimiques et moléculaires chez les patients ont montré une augmentation des concentrations sériques d’IgA polymériques et anormalement glycosylées. Ces modifications quantitatives et structurales des IgA jouent un rôle clé dans la genèse de la maladie en induisant des anomalies fonctionnelles des différents récepteurs des IgA: le RFcα (CD89) exprimé par les cellules sanguines circulantes et le récepteur de la transferrine (CD71) présent sur les cellules mésangiales. Les IgA anormales induisent la libération de CD89 soluble qui participe à la formation des complexes circulants contenant des IgA. Ces complexes se déposent secondairement dans le mésangium probablement par la fixation à un second récepteur, le CD71, surexprimé sur les cellules mésangiales des patients.
Summary
Immunoglobulin A (IgA) nephropathy or Berger’s disease is the most common form of primary glomerulonephritis in the world and one of the first cause of end-stage renal failure. IgA nephropathy is characterized by the accumulation in mesangial areas of immune complexes containing polymeric IgA1. While epidemiology and clinical studies of IgA nephropathy are well established, the mechanism(s) underlying disease development is poorly understood. The pathogenesis of this disease involves the deposition of polymeric and undergalactosylated IgA1 in the mesangium. Quantitative and structural changes of IgA1 play a key role in the development of the disease due to functional abnormalities of two IgA receptors: The FcαR (CD89) expressed by blood myeloid cells and the transferrin receptor (CD71) on mesangial cells. Abnormal IgA induce the release of soluble CD89 which is responsible for the formation of circulating IgA complexes. These complexes may be trapped by CD71 that is overexpressed on mesangial cells in IgA nephropathy patients allowing pathogenic IgA complex formation.
Appendices
Références
- 1. Galla JH. IgA nephropathy. Kidney Int 1995; 47: 377-87.
- 2. Simon P, Ramee MP, Autuly V, et al. Epidemiology of primary glomerular diseases in a French region. Variations according to period andage. Kidney Int 1994; 46: 1192-8.
- 3. Berger J, Hinglais N. Les dépôts intercapillaires d’IgA-IgG. J Urol Néphrol 1968; 74: 694-5.
- 4. Aucouturier P, Monteiro RC, Noel LH, Preud’homme JL, Lesavre P. Glomerular and serum immunoglobulin G subclasses in IgA nephropathy. Clin Immunol Immunopathol 1989; 51: 338-47.
- 5. Meadow SR, Scott DG. Berger disease: Henoch-Schonlein syndrome without the rash. J Pediatr 1985; 106: 27-32.
- 6. Berger J, Yaneva H, Nabarra B, Barbanel C. Recurrence of mesangial deposition of IgA after renal transplantation. Kidney Int 1975; 7: 232-41.
- 7. Ponticelli C, Traversi L, Feliciani A, et al. Kidney transplantation in patients with IgA mesangial glomerulonephritis. Kidney Int 2001; 60: 1948-54.
- 8. Berger J. Glomérulonéphrites idiopathiques à dépôts mésangiaux d’IgA. In: Hamburger J, Crosnier J, Grünfeld JP, eds. Néphrologie. Paris: Flammarion/Médicine-Sciences, 1979: 541-8.
- 9. Valentijn RM, Radl J, Haaijman JJ, et al. Circulating and mesangial secretory component-binding IgA-1 in primary IgA nephropathy. Kidney Int 1984; 26: 760-6.
- 10. Monteiro RC, Halbwachs-Mecarelli L, Roque-Barreira MC, et al. Charge and size of mesangial IgA in IgA nephropathy. Kidney Int 1985; 28: 666-71.
- 11. Rifai A, Small PA Jr, Teague PO, Ayoub EM. Experimental IgA nephropathy. J Exp Med 1979; 150: 1161-73.
- 12. van den Wall Bake AW, Bruijn JA, Accavitti MA, et al. Shared idiotypes in mesangial deposits in IgA nephropathy are not disease-specific. Kidney Int 1993; 44: 65-74.
- 13. de Fijter JW, Eijgenraam JW, Braam CA, et al. Deficient IgA1 immune response to nasal cholera toxin subunit B in primary IgA nephropathy. Kidney Int 1996; 50: 952-61.
- 14. Barratt J, Bailey EM, Buck KS, et al. Exaggerated systemic antibody response to mucosal Helicobacter pylori infection in IgA nephropathy. Am J Kidney Dis 1999; 33: 1049-57.
- 15. Layward L, Allen AC, Harper SJ, Hattersley JM, Feehally J. Increased and prolonged production of specific polymeric IgA after systemic immunization with tetanus toxoid in IgA nephropathy. Clin Exp Immunol 1992; 88: 394-8.
- 16. Feehally J. IgA nephropathy: a disorder of IgA production? Q J Med 1997; 90: 387-90.
- 17. Allen AC, Bailey EM, Brenchley PE, et al. Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation: observations in three patients. Kidney Int 2001; 60: 969-73.
- 18. Allen AC, Willis FR, Beattie TJ, Feehally J. Abnormal IgA glycosylation in Henoch-Schonlein purpura restricted to patients with clinical nephritis. Nephrol Dial Transplant 1998; 13: 930-4.
- 19. Sano T, Hiki Y, Kokubo T, et al. Enzymatically deglycosylated human IgA1 molecules accumulate and induce inflammatory cell reaction in rat glomeruli. Nephrol Dial Transplant 2002; 17: 50-6.
- 20. Greer MR, Barratt J, Harper SJ, Allen AC, Feehally J. The nucleotide sequence of the IgA1 hinge region in IgA nephropathy. Nephrol Dial Transplant 1998; 13: 1980-3.
- 21. Hiki Y, Tanaka A, Kokubo T, et al. Analyses of IgA1 hinge glycopeptides in IgA nephropathy by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Am Soc Nephrol 1998; 9: 577-82.
- 22. Allen AC, Topham PS, Harper SJ, Feehally J. Leucocyte beta 1,3 galactosyltransferase activity in IgA nephropathy. Nephrol Dial Transplant 1997; 12: 701-6.
- 23. 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: 2048-54.
- 24. Tomana M, Novak J, Julian BA, Matousovic 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.
- 25. Novak J, Julian BA, Tomana M, Mestecky J. Progress in molecular and genetic studies of IgA nephropathy. J Clin Immunol 2001; 21: 310-27.
- 26. Monteiro RC, van de Winkel JGJ. IgA Fc receptors. Annu Rev Immunol 2003; 21: 177-204.
- 27. Grossetete B, Launay P, Lehuen A, et al. Down-regulation of Fcα receptors on blood cells of IgA nephropathy patients: evidence for a negative regulatory role of serum IgA. Kidney Int 1998; 53: 1321-35.
- 28. Launay P, Grossetete B, Arcos-Fajardo M, et al. Fcα receptor (CD89) mediates the development of immunoglobulin A (IgA) nephropathy (Berger’s disease). Evidence for pathogenic soluble receptor-IgA complexes in patients and CD89 transgenic mice. J Exp Med 2000; 191: 1999-2009.
- 29. Muso E, Yoshida E, Takeuchi E, et al. Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice. Kidney Int 1996; 50: 1946-57.
- 30. Zheng F, Kundu GC, Zhang Z, et al. Uteroglobin is essential in preventing immunoglobulin A nephropathy in mice. Nat Med 1999; 5: 1018-25.
- 31. Silvain C, Patry C, Launay P, Lehuen A, Monteiro R. Altered expression of monocyte IgA Fc receptors is associated with defective endocytosis in patients with alcoholic cirrhosis. J Immunol 1995; 155: 1606-18.
- 32. Grossetête B, Viard JP, Lehuen A, Bach JF, Monteiro R. Impaired Fca receptor expression is linked to increased immunoglobulin A levels and disease progression in HIV-1-infected patients. AIDS 1995; 9: 229-34.
- 33. Montenegro V, Chiamolera M, Launay P, Gonçalves CR, Monteiro RC. Impaired expression of IgA Fc receptors (CD89) by blood phagocytic cells in ankylosing spondylitis. J Rheumatol 2000; 27: 411-7.
- 34. Westerhuis R, Van Zandbergen G, Verhagen NA, et al. Human mesangial cells in culture and in kidney sections fail to express Fc α receptor (CD89). J Am Soc Nephrol 1999; 10: 770-8.
- 35. Barratt J, Greer MR, Pawluczyk IZ, et al. Identification of a novel Fcα receptor expressed by human mesangial cells. Kidney Int 2000; 57: 1936-48.
- 36. Shibuya A, Sakamoto N, Shimizu Y, et al. Fc α/μ receptor mediates endocytosis of IgM-coated microbes. Nat Immunol 2000; 1: 441-6.
- 37. McDonald KJ, Cameron AJ, Allen JM, Jardine AG. Expression of Fc α/μ receptor by human mesangial cells: a candidate receptor for immune complex deposition in IgA nephropathy. Biochem Biophys Res Commun 2002; 290: 438-42.
- 38. Moura IC, Centelles MN, Arcos-Fajardo M, et al. Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy. J Exp Med 2001; 194: 417-25.
- 39. Haddad E, Moura IC, Arcos-Fajardo M, et al. Enhanced expression of the CD71 mesangial IgA1 receptor in Berger’s disease and Henoch-Schönlein nephritis: association between CD71 expression and IgA deposits. J Am Soc Nephrol 2003; 14: 327-37.
- 40. Chen A, Chen WP, Sheu LF, Lin CY. Pathogenesis of IgA nephropathy: in vitro activation of human mesangial cells by IgA immune complex leads to cytokine secretion. J Pathol 1994; 173: 119-26.
- 41. Van den Dobbelsteen ME, van der Woude FJ, Schroeijers WE, et al. Binding of dimeric and polymeric IgA to rat renal mesangial cells enhances the release of interleukin 6. Kidney Int 1994; 46: 512-9.
- 42. Duque N, Gomez-Guerrero C, Egido J. Interaction of IgA with Fcα receptors of human mesangial cells activates transcription factor nuclear factor-κB and induces expression and synthesis of monocyte chemoattractant protein-1, IL-8, and IFN-inducible protein 10. J Immunol 1997; 159: 3474-82.
- 43. Schena F, Cerullo G, Rossini M, et al. Increased risk of end-stage renal disease in familial IgA nephropathy. J Am Soc Nephrol 2002; 13: 453-60.
- 44. Hsu S, Ramirez S, Winn M, Bonventre J, Owen W. Evidence for genetic factors in the development and progression of IgA nephropathy. Kidney Int 2000; 57: 1818-35.
- 45. Ghavari A, Scolari F, Schena F, et al. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nat Genet 2000; 26: 354-7.