Hybrid protein deregulates complement in dense deposit disease

Dense deposit disease is a rare congenital disorder that is associated with complement dysfunction and often results in end stage renal disease within 10 years of the initial diagnosis. A small percentage of dense deposit disease is associated with mutations in the genes encoding factor H or C3 and autoantibody production.

In this issue of the Journal of Clinical Investigation, Peter Zipfel and colleagues at the Leibniz Institute for Natural Products Research and Infection Biology, evaluated an index family that had 2 reported cases of dense deposit disease.

The authors identified a chromosomal deletion in the complement factor H–related (CFHR) gene cluster that resulted in production of a hybrid CFHR2/CFRH5, which stabilized C3 convertase.

Treatment with soluble C1 restored C3 convertase decay and may be a promising treatment for patients with a similar refractory form of dense despite disease.