IgA Nephropathy. Facts, uncertainties, and potential causal therapy approaches
Authors:
Karel Matoušovic 1; Jiří Městecký 2; Karel Vondrák 3; Jiří Dušek 3; Eliška Chvátalová 4; Jaromír Háček 5; Milada Horynová 6; Alena Kašperová 6; Pavel Rossmann 7; Ivan Šterzl 8; Milan Raška 6
Authors place of work:
Interní klinika 2. LF UK a FNM, Praha
1; Department of Microbiology and Medicine, University of Alabama at Birmingham AL, USA a Ústav imunologie a mikrobiologie 1. LF UK, Praha
2; Pediatrická klinika 2. LF UK a FNM, Praha
3; 2. LF UK, Praha
4; Ústav patologie a molekulární medicíny 2. LF UK a FNM, Praha
5; Ústav imunologie LF UP, Olomouc
6; Mikrobiologický ústav Akademie věd České republiky, Praha
7; Endokrinologický ústav, Praha
8
Published in the journal:
Čas. Lék. čes. 2015; 154: 168-173
Category:
Review Article
Summary
IgA nephropathy is currently the most frequently investigated glomerulonephritis. The disease is defined by the presence of dominant or co-dominant deposits of IgA1 in the glomerular mesangium. Circulating immune complexes are most likely the source of the deposited IgA1. However, it is also possible that the aggregates of structurally altered IgA1 or enhanced binding to IgA receptors expressed on mesangial cells lead to deposition. The cause of the formation of immune complexes responsible for IgA nephropathy lies in the incomplete O-linked oligosaccharide side chains, which, due to the deficiency of corresponding glycosyltransferases, lack terminal galactose residues leading to the exposure of N-acetylgalactosamine. Naturally occurring antibodies of the IgG or IgA1 isotype bind to this sugar antigen. In the clinical course, we differentiate between the early stage usually characterized by hematuria, and a variable late stage characterized either by a clinical remission, by persistence of hematuria, or by increasing proteinuria and blood pressure and decreasing renal function in one third of the patients. In the early stage, it is difficult to predict the prognosis of IgA nephropathy, either on the basis of clinical presentation and morphological findings, or according to the level of galactose-deficient IgA1 in the circulation. The reliable criteria of serious prognosis emerge only in the later stages of the disease and include proteinuria, hypertension, and histologically apparent tubular atrophy and interstitial sclerosis. The dominant trend in the treatment of IgA nephropathy is the emphasis on administration of ACE inhibitors/sartans, which are introduced into the treatment at the time of microalbuminuria. If proteinuria does not decrease below 1 g/24 h, treatment with prednisone is justifiable. New findings concerning the molecular/cellular mechanism involved in the pathogenesis of IgA nephropathy suggest the possible therapeutical interference with the generation of nephritogenic immune complexes by a selective blocking of the IgA1 molecules with altered glycan structures using monovalent reagents.
Keywords:
IgA nephropathy – immunoglobulin A – O-glycosylation – immune complexes – therapy
Zdroje
1. Brod J. Acute diffuse glomerulonephritis. Am J Med 1949; 7: 317–335.
2. Rossmann P, Brod J. Klinický průběh chronické glomerulonefritidy se zřetelem k mikroskopickému obrazu v biopsii ledviny. Čas Lék čes 1968; 107: 959–964.
3. Kinkaid-Smith P, Mathew TH, Becker EC. Glomerulonephritis. morphology, natural history and treatment. New York: John Willey and Sons 1973.
4. Kerjaschki D. Molecular pathogenesis of membranous nephropathy. Kidney Int 1992; 41: 1090–1105.
5. Kerjaschki D. Pathomechanisms and molecular basis of membranous glomerulopathy. Lancet 2004; 364: 1194–1196.
6. Davies DJ, et al. Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology?. Brit Med J (Clinical Research ed.) 1982; 285: 606.
7. van der Woude FJ, et al. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener’s granulomatosis. Lancet 1985; 2: 425–529.
8. Glassock RJ. The pathogenesis of IgA nephropathy. Curr Opin Nephrol Hypertens 2011; 20: 153–160.
9. Donadio JV, Grande JP. IgA nephropathy. N Engl J Med 2002; 347: 738–748.
10. Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med 2013; 368: 2402–2414.
11. Berger J, Hinglais N. Les depôts intercapillaires d’IgA-IgG. J Urol Nephrol 1968; 74: 694–695.
12. Suzuki K, et al. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int 2003; 63: 2286–2294.
13. Monteiro RC. Role of IgA and IgA Fc receptors in inflammation. J Clin Immunol 2010; 30: 1–9.
14. Coppo R, et al. IgA1 and IgA2 immune complexes in primary IgA nephropathy and Henoch-Schönlein nephritis. Clin Exp Immunol 1984; 57: 583–590.
15. Tomana M, et al. Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG. Kidney Int 1997; 52: 509–516.
16. Tomana M, et al. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies. J Clin Invest 1999; 104: 73–81.
17. Mestecky J, et al. Defective galactosylation and clearance of IgA1 molecules as a possible etiopathogenic factor in IgA nephropathy. Contrib Nephrol 1993; 104: 172–182.
18. Mestecky J, et al. IgA nephropathy: molecular mechanisms of the disease. Annu Rev Pathol 2013; 8: 217–240.
19. Allen AC, et al. Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy. Clin Exp Immunol 1995; 100: 470–474.
20. Barratt J, et al. Immunopathogenesis of IgAN. Semin Immunopathol 2007; 29: 427–443.
21. Matoušovic K, et al. IgA nefropatie. Význam glykozylace imunoglobulinu A pro patogenezi a její klinický obraz. Čas Lék čes 2002; 141: 729–734.
22. Raska M, et al. Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells. J Mol Biol 2007; 369: 69–78.
23. Suzuki H, et al. Cytokines alter IgA1 O-glycosylation by dysregulating C1GalT1 and ST6GalNAc-II enzymes. J Biol Chem 2014; 289: 5330–5339.
24. Stuchlova Horynova M, et al. N-Acetylgalactosaminide α2,6-sialyltransferase II is a candidate enzyme for sialylation of galactose-deficient IgA1, the key autoantigen in IgA nephropathy. Nephrol Dial Transplant 2015; 30: 234–238.
25. Novak J, et al. IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells. Kidney Int 2005; 67: 504–513.
26. Julian BA, et al. Familial IgA nephropathy. Evidence of an inherited mechanism of disease. N Engl J Med 1985; 312: 202–208.
27. Julian BA, et al. IgA nephropathy: a clinical overview. Contrib Nephrol 2007; 157: 19–26.
28. Kiryluk K, et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 2014; 46: 1187–1196.
29. Feltis JT, et al. Active and chronic phases of Berger‘s disease (IgA nephropathy). Am J Kidney Dis 1984; 3: 349–356.
30. Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis 1997; 29: 829–842.
31. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society. In Coppo R et al. The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int 2010; 77: 921–927.
32. Bohle A, et al. The pathogenesis of chronic renal failure. Pathol Res Pract 1989; 185: 421–440.
33. Matoušovic K, Rossmann P. Primary glomerulonephritis. Morphological and Clinical Aspects of Diagnosis and prognosis. Praha: Academia 1994.
34. Tumlin JA. Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide. Nephrol Dial Transplant 2003; 18: 1321–1329.
35. Wallace E, et al. Immune profile of IgA-dominant diffuse proliferative glomerulonephritis. Clin Kidney J 2014; 7: 479–483.
36. KDIGO Clinical Practice Guidline for Glomerulonephriis. Kidney Int 2012; Suppl 2: 139–274.
37. Nolin L, Courteau M. Management of IgA nephropathy. Evidence-based recommendations. Kidney Int 1999; 55(Suppl 70): S56–S62.
38. Bedogna V. Effects of ACE inhibition in normotensive patients with chronic glomerular disease and normal renal function. Kidney Int 1990; 38: 101–117.
39. Hogg RJ, Southwest Pediatric Nephrology Study Group. Clinical trial to evaluate omega-3 fatty acids and alternate day prednisone in patients with IgA nephropathy: report from the Southwest Pediatric Nephrology Study Group. Clin J Am Soc Nephrol 2006; 1: 467–474.
40. Donadio JV, et al. The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group. J Am Soc Nephrol 2001; 12: 791–799.
41. Hamers-Casterman C, et al. Naturally occurring antibodies devoid of light chains. Nature 1993; 363: 446–448.
42. Rahbarizadeh F, et al. Nanobody: an old concept and new vehicle for immunotargeting. Immunol Invest 2011; 40: 299–338.
43. Kasperova A, et al. Preventing of formation of IgA1- Containing Immune Complexes in IgA 1 Nephropathy, J Am Soc Nephrol 2013; 23: 490A.
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Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental HygienistČlánok vyšiel v časopise
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