IgA Nephropathy

Isabel Beerman, Francesco Scolari, Ali Gharavi

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

This chapter gives an overview on the clinical features, pathogenesis, and genetic epidemiology of IgA nephropathy (IgAN). Manifestations of disease include persistent or episodic microscopic hematuria (60-70%), episodic macroscopic hematuria (15-45%), nephrotic syndrome (5%) and, rarely, acute reversible renal failure (3%). Disease onset commonly occurs in the second or third decade of life and most studies report a 2:1 male predominance. Mucosal infections are a precipitating or exacerbating factor in the development of disease. Humans have two IgA subtypes, IgA1 and IgA2. IgA1 contains an additional 13 amino acids in the hinge region that can be targeted by bacterial proteases. This hinge region contains O-linked glycans, a feature unique to IgA and IgD. IgAN patients have increased circulating IgA levels, with a higher proportion of the ? light chain compared to normal serum. The circulating IgA is in polymeric form, which favors immune complex formation. Inflammatory bowel disease is associated with increased incidence of IgAN. Recent data from LIGHT transgenic mice have provided insight into such secondary forms of IgAN associated with intestinal disease. LIGHT is a ligand for the lymphotoxin ? receptor (LT?R) and is expressed on activated T cells and immature dendritic cells. LT?R expression in the intestine is required for the development of mucosal lymphoid organs, and consequently for the production of IgA and recruitment of IgA precursors. The glomerulonephritis is associated with mesangial IgA deposition and 30-40-fold elevation of serum polymeric IgA levels. Increased IgA precedes overt intestinal inflammation, suggesting that increased LIGHT mediated LT?R signaling causes IgA overproduction.

Original languageEnglish
Title of host publicationGenetic Diseases of the Kidney
PublisherElsevier Inc.
Pages749-769
Number of pages21
ISBN (Print)9780124498518
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Dive into the research topics of 'IgA Nephropathy'. Together they form a unique fingerprint.

Cite this