C3 glomerulopathy refers to a group of kidney conditions characterized by innappropriate activation of an immune system response mechanism known as complement.
Normally the complement system helps to clear pathogens from the body. It consists of a number of small proteins that, upon immune activation, are broken up into fragments that bind to foreign material or pathogen-infected cells to trigger their destruction.
In C3 glomerulopathies, the complement fragments accumulate in the kidney, causing damage. In this issue of the Journal of Clinical Investigation, Santiago Rodríguez de Córdoba and colleagues at the Centro de Investigaciones Biológicas in Madrid, Spain identifed mutations in complement regulating protein, factor H, which increased complement activation.
These studies help to define how factor H functions in complement regulation and provide a greater understanding of C3 glomerulopathy pathology. As Michael Holers of the University of Colorado explains in the accompanying commentary, variants in factor H genes are linked to multiple autoimmune and inflammatory diseases. Studies like this one may help to direct the development of new therapies.
C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation
ACCOMPANYING COMMENTARY
Human C3 glomerulopathy provides unique insights into complement factor H–related protein function