IgA nephropathy pathophysiology: Difference between revisions
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The pathogenesis of IgA nephropathy is thus described by Suzuki and colleagues<ref name="pmid21949093">{{cite journal| author=Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB et al.| title=The pathophysiology of IgA nephropathy. | journal=J Am Soc Nephrol | year= 2011 | volume= 22 | issue= 10 | pages= 1795-803 | pmid=21949093 | doi=10.1681/ASN.2011050464 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21949093 }} </ref> as a 4-hit hypothesis summarized | The pathogenesis of IgA nephropathy is thus described by Suzuki and colleagues<ref name="pmid21949093">{{cite journal| author=Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB et al.| title=The pathophysiology of IgA nephropathy. | journal=J Am Soc Nephrol | year= 2011 | volume= 22 | issue= 10 | pages= 1795-803 | pmid=21949093 | doi=10.1681/ASN.2011050464 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21949093 }} </ref> as a 4-hit hypothesis that is summarized in the image below: | ||
[[File:IgAnephropathy.jpg|900px|thumb|center|Four-Hit Hypothesis of IgA Nephropathy <br> (Adapted from Suzuki H, Kiryluk K, Novak J, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011; 22(10):1795-803)]] | [[File:IgAnephropathy.jpg|900px|thumb|center|Four-Hit Hypothesis of IgA Nephropathy <br> (Adapted from Suzuki H, Kiryluk K, Novak J, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011; 22(10):1795-803)]] | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
IgA nephropathy is characterized by the presence of IgA1 deposits along the glomerular mesangium, in addition to complement C3, and properidin that are concomitantly present in almost all cases of IgA nephropathy.
The presence of increased IgA1 in IgA nephropathy has clear pathological implications due to the characteristic morphology of IgA1 subclass. The elevated levels of IgA1 in such patients is currently believed to be genetically determined. IgA1 contains a unique hinge region at a location of the immunoglobulin heavy chain between the first and second constant region domains.[1] The location is described to be rich in serine and threonine; the abundance of these amino acids at the specific site is likely to facilitate the attachment of 3-6 O-glycans, deficient in galactose, to the IgA.[1][2][3][4] Nonetheless, genetic predisposition and aberrant glycosylation do not seem to sufficiently warrant the manifestation of IgA nephropathy. In fact, antibodies against the galactose-deficient IgA1 are also needed for the pathogenesis of IgA.[1] This process is then followed by the accumulation of the formed immune complexes in the mesangial cells.[1] Finally, activated mesangial cells induce renal injury by the production and secretion of extracellular matrix, and pro-inflammatory cytokines and chemokines.[1]
The pathogenesis of IgA nephropathy is thus described by Suzuki and colleagues[1] as a 4-hit hypothesis that is summarized in the image below:
(Adapted from Suzuki H, Kiryluk K, Novak J, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011; 22(10):1795-803)
The presence of IgG and/or IgM deposits has been observed to be frequently present (22904352), whereas complement C4, C4d[5], mannose-binding lectin[6], and C5b-C9[7] have also been detected to a much less extent.
IgA frequently recurs following transplantation whereas IgA deposits in donor kidneys tend to usually resolve following recipient engraftment.[8] Both phenomena raise the suspicion of IgA nephropathy being in fact a systemic disease with renal manifestations than an isolated renal disease.[9]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB; et al. (2011). "The pathophysiology of IgA nephropathy". J Am Soc Nephrol. 22 (10): 1795–803. doi:10.1681/ASN.2011050464. PMID 21949093.
- ↑ Allen AC, Harper SJ, Feehally J (1995). "Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy". Clin Exp Immunol. 100 (3): 470–4. PMC 1534466. PMID 7774058.
- ↑ Odani H, Yamamoto K, Iwayama S, Iwase H, Takasaki A, Takahashi K; et al. (2010). "Evaluation of the specific structures of IgA1 hinge glycopeptide in 30 IgA nephropathy patients by mass spectrometry". J Nephrol. 23 (1): 70–6. PMID 20091489.
- ↑ Novak J, Julian BA, Mestecky J, Renfrow MB (2012). "Glycosylation of IgA1 and pathogenesis of IgA nephropathy". Semin Immunopathol. 34 (3): 365–82. doi:10.1007/s00281-012-0306-z. PMID 22434325.
- ↑ Espinosa M, Ortega R, Gómez-Carrasco JM, López-Rubio F, López-Andreu M, López-Oliva MO; et al. (2009). "Mesangial C4d deposition: a new prognostic factor in IgA nephropathy". Nephrol Dial Transplant. 24 (3): 886–91. doi:10.1093/ndt/gfn563. PMID 18842673.
- ↑ Roos A, Rastaldi MP, Calvaresi N, Oortwijn BD, Schlagwein N, van Gijlswijk-Janssen DJ; et al. (2006). "Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease". J Am Soc Nephrol. 17 (6): 1724–34. doi:10.1681/ASN.2005090923. PMID 16687629.
- ↑ Miyamoto H, Yoshioka K, Takemura T, Akano N, Maki S (1988). "Immunohistochemical study of the membrane attack complex of complement in IgA nephropathy". Virchows Arch A Pathol Anat Histopathol. 413 (1): 77–86. PMID 3131958.
- ↑ Silva FG, Chander P, Pirani CL, Hardy MA (1982). "Disappearance of glomerular mesangial IgA deposits after renal allograft transplantation". Transplantation. 33 (2): 241–6. PMID 7036478.
- ↑ Wyatt RJ, Julian BA (2013). "IgA nephropathy". N Engl J Med. 368 (25): 2402–14. doi:10.1056/NEJMra1206793. PMID 23782179.