Development of lupus nephritis is associated with qualitative changes in the glomerular collagen IV matrix composition

Abstract

Lupus nephritis is associated with thickening of the glomerular extracellular membranes. Distribution of collagen IV alpha-chains in the glomerular basement membrane in kidneys of lupus-prone B/W mice has been examined in this study. The results are indicative of a qualitative change in the collagen IV matrix occurring around the time of development of proteinuria, with an embryonic alpha1/alpha2 isoform replacing the normal glomerular basement membrane (GBM). These changes mimic alterations seen in Alport syndrome and coincide with an increase in collagenolytic activity within the glomerulus. It has been hypothesized that alterations in collagen matrix synthesis represent compensatory responses to an increase in GBM proteolysis and could represent an important step in the pathogenesis of nephritis through the formation of a dysfunctional glomerular filter. Also, aberrations in the collagen matrix composition could contribute to the deposition of autoantibodies within the glomerulus.