Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Inflammation Research
Published in: Inflammation Research 10/2016

01-10-2016 | Review

Immunoglobulin A nephropathy: a pathophysiology view

Authors: Rafaela Cabral Gonçalves Fabiano, Sérgio Veloso Brant Pinheiro, Ana Cristina Simões e Silva

Published in: Inflammation Research | Issue 10/2016

Login to get access

Abstract

Background and aim

IgA nephropathy is one of the leading causes of primary glomerulonephritis worldwide and an important etiology of renal disease in young adults. IgA nephropathy is considered an immune complex-mediated disease.

Methods

This review article summarizes recent evidence on the pathophysiology of IgA nephropathy.

Results

Current studies indicate an ordered sequence of multi-hits as fundamental to disease occurrence. Altered glycan structures in the hinge region of the heavy chains of IgA1 molecules act as auto-antigens, potentially triggering the production of glycan-specific autoantibodies. Recognition of novel epitopes by IgA and IgG antibodies leads to the formation of immune complexes galactose deficient-IgA1/anti-glycan IgG or IgA. Immune complexes of IgA combined with FcαRI/CD89 have also been implicated in disease exacerbation. These nephritogenic immune complexes are formed in the circulation and deposited in renal mesangium. Deposited immune complexes ultimately induce glomerular injury, through the release of pro-inflammatory cytokines, secretion of chemokines and the resultant migration of macrophages into the kidney. The TfR1/CD71 receptor has a pivotal role in mesangial cells. New signaling intracellular mechanisms have also been described.

Conclusion

The knowledge of the whole pathophysiology of this disease could provide the rational bases for developing novel approaches for diagnosis, for monitoring disease activity, and for disease-specific treatment.
Literature
1.
Coppo R, Troyanov S, Bellur S, Cattran D, Cook HT, Feehally J, Roberts ISD, Morando L, Camilla R, Tesar V, Lunberg S, Gesualdo L, Emma F, Rollino C, Amore A, Praga M, Feriozzi S, Segoloni G, Pani A, Cancarini G, Durlik M, Moggia E, Mazzucco G, Giannakakis C, Honsova E, Sundelin BB, Di Palma AM, Ferrario F, Gutierrez E, Asunis AM, Barratt J, Tardanico R, Perkowska-Ptasinska A. Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments. Kidney Int. 2014;86(4):828–36.PubMedPubMedCentralCrossRef
2.
Mestecky J, Raska M, Julian BA, Gharavi AG, Renfrow MB, Moldoveanu Z, Novak L, Matousovic K, Novak J. IgA nephropathy: molecular mechanisms of the disease. Annu Rev Pathol. 2013;8:217–40.PubMedCrossRef
3.
4.
Wyatt RJ, Kritchevsky SB, Woodford SY, Miller PM, Roy S, Holland NH, Jackson E, Bishof NA. IgA nephropathy: long-term prognosis for pediatric patients. J Pediatr. 1995;127(6):913–9.PubMedCrossRef
5.
Gutiérrez E, Zamora I, Ballarín JA, Arce Y, Jiménez S, Quereda C, Olea T, Martínez-Ara J, Segarra A, Bernis C, García A, Goicoechea M, García de Vinuesa S, Rojas-Rivera J, Praga M. Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria. J Am Soc Nephrol. 2012;23(10):1753–60.PubMedPubMedCentralCrossRef
6.
Lv J, Shi S, Xu D, Zhang H, Troyanov S, Cattran DC, Wang H. Evaluation of the Oxford classification of IgA nephropathy: a systematic review and meta-analysis. Am J Kidney Dis. 2013;62(5):891–9.PubMedCrossRef
7.
Moriyama T, Tanaka K, Iwasaki C, Oshima Y, Ochi A, Kataoka H, Itabashi M, Takei T, Uchida K, Nitta K. Prognosis in IgA nephropathy: 30-year analysis of 1,012 patients at a single center in Japan. PLoS One. 2014;9(3):e91756.PubMedPubMedCentralCrossRef
8.
Le W, Zeng C-H, Liu Z, Liu D, Yang Q, Lin R-X, Xia Z-K, Fan Z-M, Zhu G, Wu Y, Xu H, Zhai Y, Ding Y, Yang X, Liang S, Chen H, Xu F, Huang Q, Shen H, Wang J, Fogo AB, Liu Z-H. Validation of the Oxford classification of IgA nephropathy for pediatric patients from China. BMC Nephrol. 2012;13(1):158.PubMedPubMedCentralCrossRef
9.
Edström Halling S, Söderberg MP, Berg UB. Predictors of outcome in paediatric IgA nephropathy with regard to clinical and histopathological variables (Oxford classification). Nephrol Dial Transplant. 2012;27(2):715–22.PubMedCrossRef
10.
Bartosik LP, Lajoie G, Sugar L, Cattran DC. Predicting progression in IgA nephropathy. Am J Kidney Dis. 2001;38(4):728–35.PubMedCrossRef
11.
Cattran DC, Coppo R, Cook HT, Feehally J, Roberts ISD, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, D’Agati V, D’Amico G, Emancipator S, Emma F, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene H-J, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Leung CB, Li L-S, Li PKT, Liu Z-H, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76(5):534–45.PubMedCrossRef
12.
Roberts ISD, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, Cattran DC, Coppo R, D’Agati V, D’Amico G, Emancipator S, Emma F, Feehally J, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene H-J, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li L-S, Li PKT, Liu Z-H, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76(5):546–56.PubMedCrossRef
13.
Vangelista A, Frascà GM, Mondini S, Bonomini V. Idiopathic IgA mesangial nephropathy: immunohistological features. Contrib Nephrol. 1984;40:167–73.PubMedCrossRef
14.
Espinosa M, Ortega R, Gómez-Carrasco JM, López-Rubio F, López-Andreu M, López-Oliva MO, Aljama P. Mesangial C4d deposition: a new prognostic factor in IgA nephropathy. Nephrol Dial Transplant. 2009;24(3):886–91.PubMedCrossRef
15.
Sahin OZ, Yavas H, Taslı F, Gibyeli DG, Ersoy R, Uzum A, Cirit M. Prognostic value of glomerular C4d staining in patients with IgA nephritis. Int J Clin Exp Pathol. 2014;7(6):3299–304.PubMedPubMedCentral
16.
Espinosa M, Ortega R, Sánchez M, Segarra A, Salcedo MT, Gonza F, Camacho R, Espinosa M, Ortega R, Sa M, Pinedo F, Gutierrez E, Valera A, Leon M, Valdivia MA, Cabrera R, Lo K, Cobo MA, Rodriguez R, Balları J, Arce Y, Garcı B. Association of C4d deposition with clinical outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2014;9(4):897–904.PubMedPubMedCentralCrossRef
17.
Rauterberg EW, Lieberknecht HM, Wingen AM, Ritz E. Complement membrane attack (MAC) in idiopathic IgA-glomerulonephritis. Kidney Int. 1987;31(3):820–9.PubMedCrossRef
18.
Roos A, Rastaldi MP, Calvaresi N, Oortwijn BD, Schlagwein N, van Gijlswijk-Janssen DJ, Stahl GL, Matsushita M, Fujita T, van Kooten C, Daha MR. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol. 2006;17(6):1724–34.PubMedCrossRef
19.
20.
Waldherr R, Rambausek M, Duncker WD, Ritz E. Frequency of mesangial IgA deposits in a non-selected autopsy series. Nephrol Dial Transplant. 1989;4(11):943–6.PubMed
21.
Suzuki K, Honda K, Tanabe K, Toma H, Nihei H, Yamaguchi Y. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int. 2003;63(6):2286–94.PubMedCrossRef
22.
23.
Brandtzaeg P, Johansen F-E. Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev. 2005;206:32–63.PubMedCrossRef
24.
Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal Immunol. 2011;4(6):590–7.PubMedCrossRef
25.
Robert T, Berthelot L, Cambier A, Rondeau E, Monteiro RC. Molecular insights into the pathogenesis of IgA nephropathy. Trends Mol Med. 2015;21(12):762–75.PubMedCrossRef
26.
Bonner A, Almogren A, Furtado PB, Kerr MA, Perkins SJ. The nonplanar secretory IgA2 and near planar secretory IgA1 solution structures rationalize their different mucosal immune responses. J Biol Chem. 2009;284(8):5077–87.PubMedPubMedCentralCrossRef
27.
Mathias A, Pais B, Favre L, Benyacoub J, Corth B. Role of secretory IgA in the mucosal sensing of commensal bacteria. Gut Microbes. 2014;5(6):688–95.PubMedPubMedCentralCrossRef
28.
Aleyd E, Heineke MH, Van Egmond M. The era of the immunoglobulin A Fc receptor Fc a RI; its function and potential as target in disease. Immunol Rev. 2015;268(1):123–38.PubMedCrossRef
29.
30.
31.
Novak J, Julian BA, Mestecky J, Renfrow MB. Glycosylation of IgA1 and pathogenesis of IgA nephropathy. Semin. Immunopathol. 2012;34(3):365–82.PubMedCrossRef
32.
Tarelli E, Smith AC, Hendry BM, Challacombe SJ. 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;13(339):2329–35.CrossRef
33.
Takahashi K, Smith AD, Poulsen K, Kilian M, Julian BA, Mestecky J, Novak J, Renfrow MB. Naturally occurring structural isomers in serum IgA1 O-glycosylation. J Proteome Res. 2012;11(2):692–702.PubMedCrossRef
34.
Takahashi K, Wall SB, Suzuki H, Smith AD, Hall S, Poulsen K, Kilian M, Mobley JA, Julian BA, Mestecky J, Novak J, Renfrow MB. Clustered O-glycans of IgA1: defining macro- and microheterogeneity by use of electron capture/transfer dissociation. Mol Cell Proteom. 2010;9(11):2545–57.CrossRef
35.
Yu H-H, Chu K-H, Yang Y-H, Lee J-H, Wang L-C, Lin Y-T, Chiang B-L. Genetics and immunopathogenesis of IgA nephropathy. Clin Rev Allergy Immunol. 2011;41(2):198–213.PubMedCrossRef
36.
Suzuki H, Moldoveanu Z, Hall S, Brown R, Vu HL, Novak L, Julian BA, Tomana M, Wyatt RJ, Edberg JC, Alarcón GS, Kimberly RP, Tomino Y, Mestecky J, Novak J. IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J Clin Invest. 2008;118(2):629–39.PubMedPubMedCentral
37.
Hiki Y, Horii A, Iwase H, Tanaka A, Toda Y, Hotta K, Kobayashi Y. O-linked oligosaccharide on IgA1 hinge region in IgA nephropathy. Fundamental study for precise structure and possible role. Contrib Nephrol. 1995;111:73–84.PubMedCrossRef
38.
Wang Y, Zhao M-H, Zhang Y-K, Li X-M, Wang H-Y. Binding capacity and pathophysiological effects of IgA1 from patients with IgA nephropathy on human glomerular mesangial cells. Clin Exp Immunol. 2004;136(1):168–75.PubMedPubMedCentralCrossRef
39.
Novak J, Tomana M, Matousovic K, Brown R, Hall S, Novak L, Julian BA, Wyatt RJ, Mestecky J. IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells. Kidney Int. 2005;67(2):504–13.PubMedCrossRef
40.
Floege J, Moura IC, Daha MR. New insights into the pathogenesis of IgA nephropathy. Semin Immunopathol. 2014;36(4):431–42.PubMedCrossRef
41.
42.
Coppo R, Amore A, Peruzzi L, Vergano L, Camilla R. Innate immunity and IgA nephropathy. J Nephrol. 2010;23(6):626–32.PubMed
43.
Suzuki H, Fan R, Zhang Z, Brown R, Hall S, Julian BA, Chatham WW, Suzuki Y, Wyatt RJ, Moldoveanu Z, Lee JY, Robinson J, Tomana M, Tomino Y, Mestecky J, Novak J. Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest. 2009;119(6):1668–77.PubMedPubMedCentral
44.
Tomana M, Novak J, Julian BA, Matousovic K, Konecny 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(1):73–81.PubMedPubMedCentralCrossRef
45.
Barratt J, Eitner F, Feehally J, Floege J. Immune complex formation in IgA nephropathy: a case of the ‘right’ antibodies in the ‘wrong’ place at the ‘wrong’ time? Nephrol Dial Transplant. 2009;24(12):3620–3.PubMedCrossRef
46.
Schlöndorff D, Banas B. The mesangial cell revisited: no cell is an island. J Am Soc Nephrol. 2009;20(6):1179–87.PubMedCrossRef
47.
Levy M. Familial cases of Berger’s disease and anaphylactoid purpura: more frequent than previously thought. Am J Med. 1989;87(2):246–8.PubMedCrossRef
48.
Scolari F, Amoroso A, Savoldi S, Mazzola G, Prati E, Valzorio B, Viola BF, Nicola B, Movilli E, Sandrini M, Campanini M, Maiorca R. Familial clustering of IgA nephropathy: further evidence in an Italian population. Am J Kidney Dis. 1999;33(5):857–65.PubMedCrossRef
49.
Schena FP, Scivittaro V, Ranieri E. IgA nephropathy: pros and cons for a familial disease. Contrib Nephrol. 1993;104:36–45.PubMedCrossRef
50.
Rambausek M, Hartz G, Waldherr R, Andrassy K, Ritz E. Familial glomerulonephritis. Pediatr Nephrol. 1987;1(3):416–8.PubMedCrossRef
51.
Johnston PA, Brown JS, Braumholtz DA, Davison AM. Clinico-pathological 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(304):619–27.PubMed
52.
53.
Feehally J, Farrall M, Boland A, Gale DP, Gut I, Heath S, Kumar A, Peden JF, Maxwell PH, Morris DL, Padmanabhan S, Vyse TJ, Zawadzka A, Rees AJ, Lathrop M, Ratcliffe PJ. HLA has strongest association with IgA nephropathy in genome-wide analysis. J Am Soc Nephrol. 2010;21(10):1791–7.PubMedPubMedCentralCrossRef
54.
Yu X-Q, Li M, Zhang H, Low H-Q, Wei X, Wang J-Q, Sun L-D, Sim K-S, Li Y, Foo J-N, Wang W, Li Z-J, Yin X-Y, Tang X-Q, Fan L, Chen J, Li R-S, Wan J-X, Liu Z-S, Lou T-Q, Zhu L, Huang X-J, Zhang X-J, Liu Z-H, Liu J-J. A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nat Genet. 2012;44(2):178–82.CrossRef
55.
Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, Sanna-Cherchi S, Men CJ, Julian BA, Wyatt RJ, Novak J, He JC, Wang H, Lv J, Zhu L, Wang W, Wang Z, Yasuno K, Gunel M, Mane S, Umlauf S, Tikhonova I, Beerman I, Savoldi S, Magistroni R, Ghiggeri GM, Bodria M, Lugani F, Ravani P, Ponticelli C, Allegri L, Boscutti G, Frasca G, Amore A, Peruzzi L, Coppo R, Izzi C, Viola BF, Prati E, Salvadori M, Mignani R, Gesualdo L, Bertinetto F, Mesiano P, Amoroso A, Scolari F, Chen N, Zhang H, Lifton RP. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet. 2011;43(4):321–7.PubMedPubMedCentralCrossRef
56.
Genet N. HHS public xccess. 2015;46(11):1187–96.
57.
Magistroni R, DAgati VD, Appel GB, Kiryluk K. New developments in the genetics, pathogenesis, and therapy of IgA nephropathy. Kidney Int. 2015;89(1):167–75.
58.
59.
Rabb H. The T cell as a bridge between innate and adaptive immune systems: implications for the kidney. Kidney Int. 2002;61(6):1935–46.PubMedCrossRef
60.
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–84.PubMedCrossRef
61.
62.
S Sharmin, Y Shimizu, M Hagiwara, K Hirayama, A Koyama. Staphylococcus aureus antigens induce IgA-type glomerulonephritis in Balb/c mice. J Nephrol. 2004;17(4):504–11.PubMed
63.
Yamamoto C, Suzuki S, Kimura H, Yoshida H, Gejyo F. Experimental nephropathy induced by Haemophilus parainfluenzae antigens. Nephron. 2002;90(3):320–7.PubMedCrossRef
64.
Amore A, Coppo R, Nedrud JG, Sigmund N, Lamm ME, Emancipator SN. The role of nasal tolerance in a model of IgA nephropathy induced in mice by Sendai virus. Clin Immunol. 2004;113(1):101–8.PubMedCrossRef
65.
Jessen RH, Emancipator SN, Jacobs GH, Nedrud JG. Experimental IgA-IgG nephropathy induced by a viral respiratory pathogen. Dependence on antigen form and immune status. Lab Invest. 1992;67(3):379–86.PubMed
66.
Coppo R, Mazzucco G, Martina G, Roccatello D, Amore A, Novara R, Bargoni A, Piccoli G, Sena LM. Gluten-induced experimental IgA glomerulopathy. Lab Invest. 1989;60(4):499–506.PubMed
67.
Coppo R, Camilla R, Amore A, Peruzzi L, Daprà V, Loiacono E, Vatrano S, Rollino C, Sepe V, Rampino T, Dal Canton A. Toll-like receptor 4 expression is increased in circulating mononuclear cells of patients with immunoglobulin A nephropathy. Clin Exp Immunol. 2010;159(1):73–81.PubMedPubMedCentralCrossRef
68.
Suzuki H, Suzuki Y, Narita I, Aizawa M, Kihara M, Yamanaka T, Kanou T, Tsukaguchi H, Novak J, Horikoshi S, Tomino Y. Toll-like receptor 9 affects severity of IgA nephropathy. J Am Soc Nephrol. 2008;19(12):2384–95.PubMedPubMedCentralCrossRef
69.
Qin W, Zhong X, Fan JM, Zhang YJ, Liu XR, Ma XY. External suppression causes the low expression of the Cosmc gene in IgA nephropathy. Nephrol Dial Transplant. 2008;23(5):1608–14.PubMedCrossRef
70.
Buck KS, Smith AC, Molyneux K, El-Barbary H, Feehally J, Barratt J. B-cell O-galactosyltransferase activity, and expression of O-glycosylation genes in bone marrow in IgA nephropathy. Kidney Int. 2008;73(10):1128–36.PubMedCrossRef
71.
72.
Batra A, Smith AC, Feehally J, Barratt J. T-cell homing receptor expression in IgA nephropathy. Nephrol Dial Transplant. 2007;22(9):2540–8.PubMedCrossRef
73.
Andre PM, Le Pogamp P, Chevet D. Impairment of jacalin binding to serum IgA in IgA nephropathy. J Clin Lab Anal. 1990;4(2):115–9.PubMedCrossRef
74.
Tomana M, Matousovic K, Julian BA, Radl J, Konecny K, Mestecky J. Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG. Kidney Int. 1997;52(2):509–16.PubMedCrossRef
75.
Hiki Y, Odani H, Takahashi M, Yasuda Y, Nishimoto A, Iwase H, Shinzato T, Kobayashi Y, Maeda K. Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA nephropathy. Kidney Int. 2001;59(3):1077–85.PubMedCrossRef
76.
Coppo R, Amore A. Aberrant glycosylation in IgA nephropathy (IgAN). Kidney Int. 2004;65(5):1544–7.PubMedCrossRef
77.
Iwasaki H, Zhang Y, Tachibana K, Gotoh M, Kikuchi N, Kwon Y-D, Togayachi A, Kudo T, Kubota T, Narimatsu H. Initiation of O-glycan synthesis in IgA1 hinge region is determined by a single enzyme, UDP-N-acetyl-alpha-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2. J Biol Chem. 2003;278(8):5613–21.PubMedCrossRef
78.
Qin W, Zhou Q, Yang L-C, Li Z, Su B-H, Luo H, Fan J-M. Peripheral B lymphocyte beta1,3-galactosyltransferase and chaperone expression in immunoglobulin A nephropathy. J Intern Med. 2005;258(5):467–77.PubMedCrossRef
79.
Smith AC, de Wolff JF, Molyneux K, Feehally J, Barratt J. O-glycosylation of serum IgD in IgA nephropathy. J Am Soc Nephrol. 2006;17(4):1192–9.PubMedCrossRef
80.
Chintalacharuvu SR, Nagy NU, Sigmund N, Nedrud JG, Amm ME, Emancipator SN. T cell cytokines determine the severity of experimental IgA nephropathy by regulating IgA glycosylation. Clin Exp Immunol. 2001;126(2):326–33.PubMedPubMedCentralCrossRef
81.
Serino G, Sallustio F, Cox SN, Pesce F, Schena FP. Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J Am Soc Nephrol. 2012;23(5):814–24.PubMedPubMedCentralCrossRef
82.
Serino G, Sallustio F, Curci C, Cox SN, Pesce F, De Palma G. Role of let-7b in the regulation of N-acetylgalactosaminyltransferase 2 in IgA nephropathy. Nephrol Dial Transplant. 2015;30(7):1132–9.PubMedCrossRef
83.
Franc V, Řehulka P, Raus M, Stulík J, Novak J, Renfrow MB, Šebela M. Elucidating heterogeneity of IgA1 hinge-region O-glycosylation by use of MALDI-TOF/TOF mass spectrometry: role of cysteine alkylation during sample processing. J Proteom. 2013;92:299–312.CrossRef
84.
Novak J, Vu HL, Novak L, Julian BA, Mestecky J, Tomana M. Interactions of human mesangial cells with IgA and IgA-containing immune complexes. Kidney Int. 2002;62(2):465–75.PubMedCrossRef
85.
Stockert RJ, Kressner MS, Collins JC, Sternlieb I, Morell AG. IgA interaction with the asialoglycoprotein receptor. Proc Natl Acad Sci USA. 1982;79(20):6229–31.PubMedPubMedCentralCrossRef
86.
Tomana M, Kulhavy R, Mestecky J. Receptor-mediated binding and uptake of immunoglobulin A by human liver. Gastroenterology. 1988;94(3):762–70.PubMedCrossRef
87.
Novak J, Julian BA, Tomana M, Mestecky J. IgA glycosylation and IgA immune complexes in the pathogenesis of IgA nephropathy. Semin Nephrol. 2008;28(1):78–87.PubMedPubMedCentralCrossRef
88.
Nieuwhof C, Kruytzer M, Frederiks P, van Breda Vriesman PJ. Chronicity index and mesangial IgG deposition are risk factors for hypertension and renal failure in early IgA nephropathy. Am J Kidney Dis. 1998;31(6):962–70.PubMedCrossRef
89.
Berthelot L, Robert T, Vuiblet V, Tabary T, Braconnier A, Dramé M, Toupance O, Rieu P, Monteiro RC. Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes. Kidney Int. 2015;88(4):815–22.PubMedCrossRef
90.
Vuong MT, Hahn-Zoric M, Lundberg S, Gunnarsson I, van Kooten C, Wramner L, Seddighzadeh M, Fernström A, Hanson LÅ, Do LT, Jacobson SH. Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy. Kidney Int. 2010;78(12):1281–7.PubMedCrossRef
91.
Boyd JK, Barratt J. Immune complex formation in IgA nephropathy: CD89 a ‘saint’ or a ‘sinner’? Kidney Int. 2010;78(12):1211–3.PubMedCrossRef
92.
Novak J, Moldoveanu Z, Renfrow MB, Yanagihara T, Suzuki H, Raska M, Hall S, Brown R, Huang W-Q, Goepfert A, Kilian M, Poulsen K, Tomana M, Wyatt RJ, Julian BA, Mestecky J. IgA nephropathy and Henoch–Schoenlein purpura nephritis: aberrant glycosylation of IgA1, formation of IgA1-containing immune complexes, and activation of mesangial cells. Contrib Nephrol. 2007;157:134–8.PubMedCrossRef
93.
Novak J, Raskova Kafkova L, Suzuki H, Tomana M, Matousovic K, Brown R, Hall S, Sanders JT, Eison TM, Moldoveanu Z, Novak L, Novak Z, Mayne R, Julian BA, Mestecky J, Wyatt RJ. IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells. Nephrol Dial Transplant. 2011;26(11):3451–7.PubMedPubMedCentralCrossRef
94.
Launay BP, Grossetête B, Arcos-fajardo M, Gaudin E, Torres SP, Beaudoin L, De Serre NP, Lehuen A, Monteiro RC. Fc-alpha receptor (CD89) mediates the development of immunoglobulin A (IgA) nephropathy (Berger’ s disease): evidence for pathogenic soluble receptor—IgA complexes in patients and CD89 ransgenic mice. J Exp Med. 2000;191(11):1999–2009.PubMedPubMedCentralCrossRef
95.
Berthelot L, Papista C, Maciel TT, Biarnes-Pelicot M, Tissandie E, Wang PHM, Tamouza H, Jamin A, Bex-Coudrat J, Gestin A, Boumediene A, Arcos-Fajardo M, England P, Pillebout E, Walker F, Daugas E, Vrtosvnik F, Flamant M, Benhamou M, Cogné M, Moura IC, Monteiro RC. Transglutaminase is essential for IgA nephropathy development acting through IgA receptors. J Exp Med. 2012;209(4):793–806.PubMedPubMedCentralCrossRef
96.
Leung JC, Tsang AW, Chan DT, Lai KN. Absence of CD89, polymeric immunoglobulin receptor, and asialoglycoprotein receptor on human mesangial cells. J Am Soc Nephrol. 2000;11(2):241–9.PubMed
97.
Kaneko Y, Otsuka T, Tsuchida Y, Gejyo F, Narita I. Integrin alpha1/beta1 and alpha2/beta1 as a receptor for IgA1 in human glomerular mesangial cells in IgA nephropathy. Int Immunol. 2012;24(4):219–32.PubMedCrossRef
98.
Moura IC, Arcos-Fajardo M, Gdoura A, Leroy V, Sadaka C, Mahlaoui N, Lepelletier Y, Vrtovsnik F, Haddad E, Benhamou M, Monteiro RC. Engagement of transferrin receptor by polymeric IgA1: evidence for a positive feedback loop involving increased receptor expression and mesangial cell proliferation in IgA nephropathy. J Am Soc Nephrol. 2005;16(9):2667–76.PubMedCrossRef
99.
Tamouza H, Chemouny JM, Raskova Kafkova L, Berthelot L, Flamant M, Demion M, Mesnard L, Paubelle E, Walker F, Julian BA, Tissandié E, Tiwari MK, Camara NOS, Vrtovsnik F, Benhamou M, Novak J, Monteiro RC, Moura IC. The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy. Kidney Int. 2012;82(12):1284–96.PubMedCrossRef
100.
101.
Wyatt RJ, Julian BA. Activation of complement in IgA nephropathy. Am J Kidney Dis. 1988;12(5):437–42.PubMedCrossRef
102.
Maillard N, Wyatt RJ, Julian BA, Kiryluk K, Gharavi A, Fremeaux-Bacchi V, Novak J. Current understanding of the role of complement in IgA nephropathy. J Am Soc Nephrol. 2015;26(7):1503–12.PubMedPubMedCentralCrossRef
103.
Nasri H, Ahmadi A, Rafieian-Kopaei M, Bashardoust B, Nasri P, Mubarak M. Association of glomerular C4d deposition with various demographic data in IgA nephropathy patients; a preliminary study. J Nephropathol. 2015;4(1):19–23.PubMedPubMedCentral
104.
Espinosa M, Ortega R, Sánchez M, Segarra A, Salcedo MT, González F, Camacho R, Valdivia MA, Cabrera R, López K, Pinedo F, Gutierrez E, Valera A, Leon M, Cobo MA, Rodriguez R, Ballarín J, Arce Y, García B, Muñoz MD, Praga M. Association of C4d deposition with clinical outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2014;9(5):897–904.PubMedPubMedCentralCrossRef
105.
Ohsawa I, Ishii M, Ohi H, Tomino Y. Pathological scenario with the mannose-binding lectin in patients with IgA nephropathy. J Biomed Biotechnol. 2012;2012:476739.PubMedPubMedCentralCrossRef
106.
Liu L-L, Liu N, Chen Y, Wang L-N, Jiang Y, Wang J, Li X-L, Yao L, Fan Q-L. Glomerular mannose-binding lectin deposition is a useful prognostic predictor in immunoglobulin A nephropathy. Clin Exp Immunol. 2013;174(1):152–60.PubMedPubMedCentralCrossRef
107.
Ohsawa I, Ishii M, Ohi H, Tomino Y. Pathological scenario with the mannose-binding lectin in patients with IgA nephropathy. J Biomed Biotechnol. 2012;2012(Figure 1):476739.PubMedPubMedCentral
108.
Moura IC, Benhamou M, Launay P, Vrtovsnik F, Blank U, Monteiro RC. The glomerular response to IgA deposition in IgA nephropathy. Semin Nephrol. 2008;28(1):88–95.PubMedCrossRef
109.
Lai KN, Leung JCK, Chan LYY, Guo H, Tang SCW. Interaction between proximal tubular epithelial cells and infiltrating monocytes/T cells in the proteinuric state. Kidney Int. 2007;71(6):526–38.PubMedCrossRef
Metadata
Title
Immunoglobulin A nephropathy: a pathophysiology view
Authors
Rafaela Cabral Gonçalves Fabiano
Sérgio Veloso Brant Pinheiro
Ana Cristina Simões e Silva
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 10/2016
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-016-0962-x

Other articles of this Issue 10/2016

Inflammation Research 10/2016 Go to the issue

Original Research Paper

Immunobiotic Lactobacillus strains reduce small intestinal injury induced by intraepithelial lymphocytes after Toll-like receptor 3 activation

Original Research Paper

The modulation of Th2 immune pathway in the immunosuppressive effect of human umbilical cord mesenchymal stem cells in a murine asthmatic model

Original Research Paper

PGK1, a glucose metabolism enzyme, may play an important role in rheumatoid arthritis

Original Research Paper

NOD2 induces autophagy to control AIEC bacteria infectiveness in intestinal epithelial cells

Original Research Paper

Polymorphisms in complement genes and risk of preeclampsia in Taiyuan, China

Original Research Paper

GM-CSF and GM-CSF receptor have regulatory role in transforming rat mesenteric mesothelial cells into macrophage-like cells
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits