A rare C3 glomerulopathy familial case: Insights and models

C3 glomerulopathy (C3G) is a group of rare kidney diseases that develop from an uncontrolled activation of the complement system. The complement system helps the innate and adaptive immune systems in fighting off infections and getting rid of substances our body no longer requires. In C3G, when complement activation is increased, a complement protein called C3 accumulates in the kidney and causes harm to the tissue. Within 10 years of a patient being diagnosed with C3G, 30-50% of patients will have permanent kidney damage. The current treatments available for C3G patients are imperfect and thus require further improvements.

A common early sign of complement dysregulation is low serum C3 levels, but to confirm diagnosis, the kidney tissue needs to be analyzed for build-up of the C3 protein. Genetic defects and/or antibodies that attack our own tissues and organs contribute to the disease. The complexity of C3G complicates prediction and interpretation of disease symptoms. In this thesis, a family with C3G, which are rare, is described and was thoroughly studied to gain knowledge of how abnormal complement activity is causing injury to the kidney. Our results identified a lack of functional protein important for preventing excessive complement activation. We also created a mouse model to mirror this family’s disease to learn, using techniques not suitable for humans, how this disease is developing and to discover potential treatment options for C3G patients.