An update on the pathogenesis and treatment of IgA nephropathy

Kidney International

Volumn 81, Issue 9, 2012, Pages 833-843

  Boyd, Joanna K ^a,b   Cheung, Chee K ^a,b   Molyneux, Karen ^a,b   Feehally, John ^a,b   Barratt, Jonathan ^a,b  

^a LEICESTER GENERAL HOSPITAL   (United Kingdom)

^b UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

IgA; IgA deposition; IgA nephropathy; immune complexes

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; AZATHIOPRINE; BUDESONIDE; CORTICOSTEROID; CYCLOPHOSPHAMIDE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; FISH OIL; IMMUNOGLOBULIN A; IMMUNOGLOBULIN A1; IMMUNOGLOBULIN G; IMMUNOSUPPRESSIVE AGENT; METHYLPREDNISOLONE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; NEFECON R; PREDNISONE; RAPAMYCIN; UNCLASSIFIED DRUG;

ANTIGEN ANTIBODY COMPLEX; B LYMPHOCYTE; BLOOD PRESSURE; CHRONIC KIDNEY DISEASE; CYTOPENIA; DISEASE COURSE; DRUG MEGADOSE; GASTROINTESTINAL SYMPTOM; GLYCOSYLATION; HIGH RISK PATIENT; HUMAN; HUMAN TISSUE; IMMUNE COMPLEX DEPOSITION; IMMUNOGLOBULIN A NEPHROPATHY; INTERSTITIAL NEPHRITIS; KIDNEY BIOPSY; LIVER TOXICITY; PATHOGENESIS; PRIORITY JOURNAL; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; TONSILLECTOMY;

EID: 84859783352     PISSN: 00852538     EISSN: 15231755     Source Type: Journal    
DOI: 10.1038/ki.2011.501     Document Type: Review

References (110)

1. Berger J, Hinglais N. Les depots intercapillaries d'IgA-IgG. J Urol Nephrol 1968; 74: 694-695.
2. 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: 969-973. (Pubitemid 34205796)
3. Moldoveanu Z, Wyatt RJ, Lee JY et al. Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels. Kidney Int 2007; 71: 1148-1154. (Pubitemid 46809135)
4. Allen AC, Bailey EM, Buck KS et al. O-glycosylation of mesangial IgA1 in IgA nephropathy. J Am Soc Nephrol 1999; 10: 506.
5. Allen AC, Harper SJ, Feehally J. Galactosylation of N-and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy. Clin Exp Immunol 1995; 100: 470-474.
6. Hiki Y, Kokubo T, Iwase H et al. Underglycosylation of IgA1 hinge plays a certain role for its glomerular deposition in IgA nephropathy. J Am Soc Nephrol 1999; 10: 760-769. (Pubitemid 29149526)
7. Tarelli E, Smith AC, Hendry BM et al. Human serum IgA1 is substituted with up to six O-glycans as shown by matrix assisted laser desorption ionisation time-of-flight mass spectrometry. Carbohydr Res 2004; 339: 2329-2335. (Pubitemid 39165126)
8. Suzuki H, Moldoveanu Z, Hall S et al. IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J Clin Invest 2008; 118: 629-639. (Pubitemid 351206552)
9. Inoue T, Sugiyama H, Kikumoto Y et al. Downregulation of the beta1, 3-galactosyltransferase gene in tonsillar B lymphocytes and aberrant lectin bindings to tonsillar IgA as a pathogenesis of IgA nephropathy. Contrib Nephrol 2007; 157: 120-124.
10. Li GS, Zhang H, Lv JC et al. Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy. Kidney Int 2007; 71: 448-453.
11. Yamada K, Kobayashi N, Ikeda T et al. Down-regulation of core 1 {beta}1,3-galactosyltransferase and Cosmc by Th2 cytokine alters O-glycosylation of IgA1. Nephrol Dial Transplant 2010; 25: 3890-3897.
12. Royle L, Roos A, Harvey DJ et al. Secretory IgA N-and O-glycans provide a link between the innate and adaptive immune systems. J Biol Chem 2003; 278: 20140-20153. (Pubitemid 36799209)
13. Smith AC, Molyneux K, Feehally J et al. O-glycosylation of serum IgA1 antibodies against mucosal and systemic antigens in IgA nephropathy. J Am Soc Nephrol 2006; 17: 3520-3528. (Pubitemid 44865295)
14. Smith AC, de Wolff JF, Molyneux K et al. O-glycosylation of serum IgD in IgA nephropathy. J Am Soc Nephrol 2006; 17: 1192-1199.
15. Gharavi AG, Moldoveanu Z, Wyatt RJ et al. Aberrant IgA1 glycosylation is inherited in familial and sporadic IgA nephropathy. J Am Soc Nephrol 2008; 19: 1008-1014.
16. Hastings MC, Moldoveanu Z, Julian BA et al. Galactose-deficient IgA1 in african americans with IgA nephropathy: serum levels and heritability. Clin J Am Soc Nephrol 2010; 5: 2069-2074.
17. Lin X, Ding J, Zhu L et al. Aberrant galactosylation of IgA1 is involved in the genetic susceptibility of Chinese patients with IgA nephropathy. Nephrol Dial Transplant 2009; 24: 3372-3375.
18. Novak J, Julian BA, Tomana M et al. IgA glycosylation and IgA immune complexes in the pathogenesis of IgA nephropathy. Semin Nephrol 2008; 28: 78-87.
19. Kokubo T, Hiki Y, Iwase H et al. Evidence for involvement of IgA1 hinge glycopeptide in the IgA1-IgA1 interaction in IgA nephropathy. J Am Soc Nephrol 1997; 8: 915-919.
20. Suzuki H, Fan R, Zhang Z et al. Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 2009; 119: 1668-1677.
21. Tomana M, Matousovic K, Julian BA et al. Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG. Kidney Int 1997; 52: 509-516. (Pubitemid 27359597)
22. Feehally J, Farrall M, Boland A et al. HLA has strongest association with IgA nephropathy in genome-wide analysis. J Am Soc Nephrol 2010; 21: 1791-1797.
23. Gharavi AG, Kiryluk K, Choi M et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet 2011; 43: 321-327.
24. Coppo R, Camilla R, Alfarano A et al. Upregulation of the immunoproteasome in peripheral blood mononuclear cells of patients with IgA nephropathy. Kidney Int 2009; 75: 536-541.
25. Launay P, Grossetete B, Arcos-Fajardo M et al. Fcalpha 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. (Pubitemid 30390361)
26. Van Der Boog PJ, De Fijter JW, Van Kooten C et al. Complexes of IgA with FcalphaRI/CD89 are not specific for primary IgA nephropathy. Kidney Int 2003; 63: 514-521. (Pubitemid 36126797)
27. Vuong MT, Hahn-Zoric M, Lundberg S et al. Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy. Kidney Int 2010; 78: 1281-1287.
28. Macpherson AJ, McCoy KD, Johansen FE et al. The immune geography of IgA induction and function. Mucosal Immunol 2008; 1: 11-22.
29. Pakkanen SH, Kantele JM, Moldoveanu Z et al. Expression of homing receptors on IgA1 and IgA2 plasmablasts in blood reflects differential distribution of IgA1 and IgA2 in various body fluids. Clin Vaccine Immunol 2010; 17: 393-401.
30. Conley ME, Cooper MD, Michael AF. Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus. J Clin Invest 1980; 66: 1432-1436. (Pubitemid 11205607)
31. Layward L, Allen AC, Hattersley JM et al. Low antibody affinity restricted to the IgA isotype in IgA nephropathy. Clin Exp Immunol 1994; 95: 35-41. (Pubitemid 24207100)
32. Harper SJ, Pringle JH, Wicks AC et al. Expression of J chain mRNA in duodenal IgA plasma cells in IgA nephropathy. Kidney Int 1994; 45: 836-844. (Pubitemid 24094497)
33. Harper SJ, Allen AC, Pringle JH et al. Increased dimeric IgA producing B cells in the bone marrow in IgA nephropathy determined by in situ hybridisation for J chain mRNA. J Clin Pathol 1996; 49: 38-42. (Pubitemid 26037051)
34. Buren M, Yamashita M, Suzuki Y et al. Altered expression of lymphocyte homing chemokines in the pathogenesis of IgA nephropathy. Contrib Nephrol 2007; 157: 50-55.
35. Batra A, Smith AC, Feehally J et al. T-cell homing receptor expression in IgA nephropathy. Nephrol Dial Transplant 2007; 22: 2540-2548. (Pubitemid 47365518)
36. Kennel-De March A, Bene MC, Hurault de Ligny B et al. Enhanced expression of CD31 and CD54 on tonsillar high endothelial venules in IgA nephropathy. Clin Immunol Immunopathol 1997; 84: 158-165. (Pubitemid 27353467)
37. Akira S. Mammalian Toll-like receptors. Curr Opin Immunol 2003; 15: 5-11. (Pubitemid 35454185)
38. Suzuki H, Suzuki Y, Narita I et al. Toll-like receptor 9 affects severity of IgA nephropathy. J Am Soc Nephrol 2008; 19: 2384-2395.
39. Park HJ, Hahn WH, Suh JS et al. Association between Toll-like receptor 10 (TLR10) gene polymorphisms and childhood IgA nephropathy. Eur J Pediatr 2011; 170: 503-509.
40. Qin W, Zhong X, Fan JM et al. External suppression causes the low expression of the Cosmc gene in IgA nephropathy. Nephrol Dial Transplant 2008; 23: 1608-1614. (Pubitemid 351767729)
41. Blaas SH, Stieber-Gunckel M, Falk W et al. CpG-oligodeoxynucleotides stimulate immunoglobulin A secretion in intestinal mucosal B cells. Clin Exp Immunol 2009; 155: 534-540.
42. Coppo R, Camilla R, Amore A et al. Toll-like receptor 4 expression is increased in circulating mononuclear cells of patients with immunoglobulin A nephropathy. Clin Exp Immunol 2010; 159: 73-81.
43. Coppo R, Amore A, Gianoglio B et al. Serum IgA and macromolecular IgA reacting with mesangial matrix components. Contrib Nephrol 1993; 104: 162-171.
44. 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. (Pubitemid 28482152)
45. Cattran DC, Coppo R, Cook HT et al. The Oxford Classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 2009; 76: 534-545.
46. Novak J, Tomana M, Matousovic K et al. IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells. Kidney Int 2005; 67: 504-513. (Pubitemid 40139842)
47. Novak J, Vu HL, Novak L et al. Interactions of human mesangial cells with IgA and IgA-containing immune complexes. Kidney Int 2002; 62: 465-475. (Pubitemid 34779757)
48. 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: 417-425. (Pubitemid 32835038)
49. Lai KN, Leung JC, Chan LY et al. Podocyte injury induced by mesangialderived cytokines in IgA nephropathy. Nephrol Dial Transplant 2009; 24: 62-72.
50. El Karoui K, Hill GS, Karras A et al. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies. Kidney Int 2011; 79: 643-654.
51. Hill GS, Karoui KE, Karras A et al. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies. Kidney Int 2011; 79: 635-642.
52. Chan LY, Leung JC, Tsang AW et al. Activation of tubular epithelial cells by mesangial-derived TNF-alpha: glomerulotubular communication in IgA nephropathy. Kidney Int 2005; 67: 602-612. (Pubitemid 40139851)
53. Matousovic K, Novak J, Yanagihara T et al. IgA-containing immune complexes in the urine of IgA nephropathy patients. Nephrol Dial Transplant 2006; 21: 2478-2484. (Pubitemid 44644520)
54. Bisceglia L, Cerullo G, Forabosco P et al. Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci. Am J Hum Genet 2006; 79: 1130-1134. (Pubitemid 44853485)
55. Gharavi AG, Yan Y, Scolari F et al. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nat Genet 2000; 26: 354-357.
56. Paterson AD, Liu XQ, Wang K et al. Genome-wide linkage scan of a large family with IgA nephropathy localizes a novel susceptibility locus to chromosome 2q36. J Am Soc Nephrol 2007; 18: 2408-2415. (Pubitemid 47203857)
57. Schena FP. Immunoglobulin a nephropathy with mild renal lesions: a call in the forest for physicians and nephrologists. Am J Med 2001; 110: 499-500.
58. Scholl U, Wastl U, Risler T et al. The 'point of no return' and the rate of progression in the natural history of IgA nephritis. Clin Nephrol 1999; 52: 285-292. (Pubitemid 29524960)
59. Appel GB, Waldman M. The IgA nephropathy treatment dilemma. Kidney Int 2006; 69: 1939-1944. (Pubitemid 43924256)
60. Barratt J, Feehally J. Treatment of IgA nephropathy. Kidney Int 2006; 69: 1934-1938. (Pubitemid 43924255)
61. Szeto CC, Lai FM, To KF et al. The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am J Med 2001; 110: 434-437.
62. Reich HN, Troyanov S, Scholey JW et al. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 2007; 18: 3177-3183. (Pubitemid 350223978)
63. Praga M, Gutierrez E, Gonzalez E et al. Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol 2003; 14: 1578-1583. (Pubitemid 36687059)
64. Li PK, Leung CB, Chow KM et al. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis 2006; 47: 751-760.
65. Coppo R, Peruzzi L, Amore A et al. IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria. J Am Soc Nephrol 2007; 18: 1880-1888. (Pubitemid 46870324)
66. Russo D, Minutolo R, Pisani A et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis 2001; 38: 18-25. (Pubitemid 32611753)
67. Mann JF, Schmieder RE, McQueen M et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008; 372: 547-553.
68. Tang SC, Lin M, Tam S et al. Aliskiren combined with losartan in immunoglobulin A nephropathy: an open-labeled pilot study. Nephrol Dial Transplant 2011; doi:10.1093/ndt/gfr349 (e-pub ahead of print).
69. Coppo R, Feehally J, Glassock RJ. IgA nephropathy at two score and one. Kidney Int 2010; 77: 181-186.
70. Grande JP, Donadio Jr JV. Dietary fish oil supplementation in IgA nephropathy: a therapy in search of a mechanism? [editorial]. Nutrition 1998; 14: 240-242.
71. Donadio Jr JV, Bergstralh EJ, Offord KP et al. A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group [see comments]. N Engl J Med 1994; 331: 1194-1199. (Pubitemid 24331337)
72. Donadio Jr JV, Grande JP, Bergstralh EJ 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 1999; 10: 1772-1777. (Pubitemid 29364676)
73. Hogg RJ, Lee J, Nardelli N et al. 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.
74. Strippoli GF, Manno C, Schena FP. An 'evidence-based' survey of therapeutic options for IgA nephropathy: assessment and criticism. Am J Kidney Dis 2003; 41: 1129-1139. (Pubitemid 36637967)
75. Coppo R. Can a dysregulated mucosal immune system in IgA nephropathy be controlled by tonsillectomy? Nephrol Dial Transplant 2010; 25: 2395-2397.
76. Hotta O, Miyazaki M, Furuta T et al. Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy. Am J Kidney Dis 2001; 38: 736-743.
77. Xie Y, Nishi S, Ueno M et al. The efficacy of tonsillectomy on long-term renal survival in patients with IgA nephropathy. Kidney Int 2003; 63: 1861-1867. (Pubitemid 36513334)
78. Rasche FM, Schwarz A, Keller F. Tonsillectomy does not prevent a progressive course in IgA nephropathy. Clin Nephrol 1999; 51: 147-152. (Pubitemid 29116416)
79. Piccoli A, Codognotto M, Tabbi MG et al. Influence of tonsillectomy on the progression of mesangioproliferative glomerulonephritis. Nephrol Dial Transplant 2010; 25: 2583-2589.
80. Komatsu H, Fujimoto S, Hara S et al. Effect of tonsillectomy plus steroid pulse therapy on clinical remission of IgA nephropathy: a controlled study. Clin J Am Soc Nephrol 2008; 3: 1301-1307.
81. Wang Y, Chen J, Chen Y et al. A meta-analysis of the clinical remission rate and long-term efficacy of tonsillectomy in patients with IgA nephropathy. Nephrol Dial Transplant 2011; 26: 1923-1931.
82. Pozzi C, Andrulli S, Del Vecchio L et al. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol 2004; 15: 157-163. (Pubitemid 38020707)
83. Manno C, Torres DD, Rossini M et al. Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transplant 2009; 24: 3694-3701.
84. Lv J, Zhang H, Chen Y et al. Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis 2009; 53: 26-32.
85. Eitner F, Floege J. Glomerular disease: ACEIs with or without corticosteroids in IgA nephropathy? Nat Rev Nephrol 2010; 6: 252-254.
86. Zhou YH, Tang LG, Guo SL et al. Steroids in the treatment of IgA nephropathy to the improvement of renal survival: a systematic review and meta-analysis. PLoS One 2011; 6: e18788.
87. Lai KN, Lai FM, Ho CP et al. Corticosteroid therapy in IgA nephropathy with nephrotic syndrome: a long-term controlled trial. Clin Nephrol 1986; 26: 174-180. (Pubitemid 16025306)
88. Pozzi C, Andrulli S, Pani A et al. Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy. J Am Soc Nephrol 2010; 21: 1783-1790.
89. Ballardie FW, Roberts IS. Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol 2002; 13: 142-148. (Pubitemid 34042021)
90. Frisch G, Lin J, Rosenstock J et al. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant 2005; 20: 2139-2145. (Pubitemid 41510089)
91. Maes BD, Oyen R, Claes K et al. Mycophenolate mofetil in IgA nephropathy: results of a 3-year prospective placebo-controlled randomized study. Kidney Int 2004; 65: 1842-1849. (Pubitemid 38591034)
92. Xu G, Tu W, Jiang D et al. Mycophenolate mofetil treatment for IgA nephropathy: a meta-analysis. Am J Nephrol 2008; 29: 362-367.
93. Tang SC, Tang AW, Wong SS et al. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int 2010; 77: 543-549.
94. Cruzado JM, Poveda R, Ibernon M et al. Low-dose sirolimus combined with angiotensin-converting enzyme inhibitor and statin stabilizes renal function and reduces glomerular proliferation in poor prognosis IgA nephropathy. Nephrol Dial Transplant 2011; 26: 3596-3602.
95. Krebs S, Omer B, Omer TN et al. Wormwood (Artemisia absinthium) for poorly responsive early-stage IgA nephropathy: a pilot uncontrolled trial. Am J Kidney Dis 2010; 56: 1095-1099.
96. Tumlin JA, Hennigar RA. Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy. Semin Nephrol 2004; 24: 256-268. (Pubitemid 38685994)
97. Ponticelli C, Traversi L, Feliciani A et al. Kidney transplantation in patients with IgA mesangial glomerulonephritis. Kidney Int 2001; 60: 1948-1954. (Pubitemid 33000001)
98. Ponticelli C, Glassock RJ. Posttransplant recurrence of primary glomerulonephritis. Clin J Am Soc Nephrol 2010; 5: 2363-2372.
99. Chandrakantan A, Ratanapanichkich P, Said M et al. Recurrent IgA nephropathy after renal transplantation despite immunosuppressive regimens with mycophenolate mofetil. Nephrol Dial Transplant 2005; 20: 1214-1221. (Pubitemid 40862113)
100. Chailimpamontree W, Dmitrienko S, Li G et al. Probability, predictors, and prognosis of posttransplantation glomerulonephritis. J Am Soc Nephrol 2009; 20: 843-851.
101. Berthoux F, El Deeb S, Mariat C et al. Antithymocyte globulin (ATG) induction therapy and disease recurrence in renal transplant recipients with primary IgA nephropathy. Transplantation 2008; 85: 1505-1507.
102. Clayton P, McDonald S, Chadban S. Steroids and recurrent IgA nephropathy after kidney transplantation. Am J Transplant 2011; 11: 1645-1649.
103. Courtney AE, McNamee PT, Nelson WE et al. Does angiotensin blockade influence graft outcome in renal transplant recipients with IgA nephropathy? Nephrol Dial Transplant 2006; 21: 3550-3554. (Pubitemid 44817108)
104. Eitner F, Ackermann D, Hilgers RD et al. Supportive versus immunosuppressive therapy of progressive IgA nephropathy (STOP) IgAN trial: rationale and study protocol. J Nephrol 2008; 21: 284-289.
105. Smerud HK, Barany P, Lindstrom K et al. New treatment of IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria. Nephrol Dial Transplant 2011; 26: 3237-3242.
106. Dunne A, Marshall NA, Mills KH. TLR based therapeutics. Curr Opin Pharmacol 2011; 11: 404-411.
107. Guiducci C, Gong M, Xu Z et al. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 2010; 465: 937-941.
108. Kyburz D, Brentano F, Gay S. Mode of action of hydroxychloroquine in RA-evidence of an inhibitory effect on Toll-like receptor signaling. Nat Clin Pract Rheumatol 2006; 2: 458-459. (Pubitemid 44340417)
109. Ziegler HK, Unanue ER. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci USA 1982; 79: 175-178. (Pubitemid 12181509)
110. Reid S, Cawthon PM, Craig JC et al. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev 2011; (3): CD003962.