C3G is defined by a specific finding on renal biopsy: a dominant pattern of C3 fragment deposition on immunofluorescence. The primary pathogenic mechanism of this group of diseases involves abnormal control of the alternative complement pathway. In these patients complement C3, factor B and properdin levels are lower than in controls while levels of complement breakdown products are higher. Signs of terminal complement pathway dysregulation can also be seen and include a decrease in C5 and an increase in soluble C5b-9. Biomarker profiling substantiates the link between complement dysregulation and C3G and can identify C3G inter-disease differences. Complement abnormalities, such as the level of soluble C5b-9, can form the basis of an expanded definition of C3G disease and may be helpful in determining therapy.
Atypical Hemolytic Uremic Syndrome
In aHUS the presence of anti-factor H autoantibodies may have bearing on disease treatment. This specific subtype of aHUS should be considered in children presenting with aHUS between the ages of 5-13 years, especially if they also have signs of severe hemolysis and renal failure. In this patient cohort, the frequency of extrarenal manifestations such as hepatic disease, neurological features and diarrhea is increased as compared to aHUS patients with complement gene mutations. More than 60% of children with anti-factor H autoantibodies also have low levels of C3.