IgA nephropathy: an update.
OBJECTIVE
The elution of nephrectomy specimens from patients with IgA nephropathy yields IgA1 with galactose-deficient glycans in the hinge region. In this review, we summarize recent advances in our understanding of the role of the aberrant immunoglobulin in the pathogenesis of this form of glomerulonephritis. In the absence of a disease-specific therapy, we discuss current therapeutic approaches.


RESULTS
Galactose-deficient IgA1 forms macromolecular complexes that bind to mesangial cells and stimulate them to proliferate, synthesize various cytokines and chemokines, and secrete extracellular matrix proteins. Whereas progress has been made in understanding the glycosylation pathways of IgA1 O-linked glycans and binding galactose-deficient IgA1-complexes to mesangial cells, there is still no IgA nephropathy-specific therapy. The current approach to suppress the effects of angiotensin II, by angiotensin-converting enzyme inhibitors, angiotensin II receptor type 1 blockers, or both, as a cornerstone of the therapy of IgA nephropathy has been strengthened by recent studies. Treatment with glucocorticoids, cyclophosphamide, or both, may be appropriate for a subset of IgA nephropathy patients.


CONCLUSIONS
A better understanding of the mechanisms underlying the synthesis of galactose-deficient IgA1, the formation of circulating immune complexes, and interactions with mesangial cells will provide further insights into the pathogenetic mechanisms that culminate in the glomerular and interstitial damage of IgA nephropathy, and could identify novel therapeutic targets in the prevention and management of this renal disease.
Julian
Bruce A
BA
Department of aMedicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. bjulian@uab.edu
Novak
Jan
J
D005920:Glomerular Mesangium / Q000276:immunology*; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*
D007070:Immunoglobulin A; C042441:glycosylated IgA