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Pediatr Nephrol. 2018 May;33(5):763-777. doi: 10.1007/s00467-017-3699-z. Epub 2017 Jun 17.

New insights into the pathogenesis of IgA nephropathy.

Author information

1
Department of Renal Medicine, Tan Tock Seng Hospital, Singapore, Singapore.
2
Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester, LE1 7RH, UK.
3
The John Walls Renal Unit, Leicester General Hospital, Leicester, UK.
4
Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester, LE1 7RH, UK. jb81@le.ac.uk.
5
The John Walls Renal Unit, Leicester General Hospital, Leicester, UK. jb81@le.ac.uk.

Abstract

IgA nephropathy is the most common form of glomerulonephritis in many parts of the world and remains an important cause of end-stage renal disease. Current evidence suggests that IgA nephropathy is not due to a single pathogenic insult, but rather the result of multiple sequential pathogenic "hits". An abnormally increased level of circulating poorly O-galactosylated IgA1 and the production of O-glycan-specific antibodies leads to the formation of IgA1-containing immune complexes, and their subsequent mesangial deposition results in inflammation and glomerular injury. While this general framework has formed the foundation of our current understanding of the pathogenesis of IgA nephropathy, much work is ongoing to try to precisely define the genetic, epigenetic, immunological, and molecular basis of IgA nephropathy. In particular, the precise origin of poorly O-galactosylated IgA1 and the inciting factors for the production of O-glycan-specific antibodies continue to be intensely evaluated. The mechanisms responsible for mesangial IgA1 deposition and subsequent renal injury also remain incompletely understood. In this review, we summarize the current understanding of the key steps involved in the pathogenesis of IgA nephropathy. It is hoped that further advances in our understanding of this common glomerulonephritis will lead to novel diagnostic and prognostic biomarkers, and targeted therapies to ameliorate disease progression.

KEYWORDS:

IgA nephropathy; IgA1; Immune complexes; O-galactosylation; Pathogenesis

PMID:
28624979
PMCID:
PMC5861174
DOI:
10.1007/s00467-017-3699-z
[Indexed for MEDLINE]
Free PMC Article

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