C3 nephritic factor has been shown to be due to an IgG autoantibody to the alternate pathway C3 convertase, which blocks the action of the inhibitors (Factors H and I) in destroying the C3 convertase. Since all sera contain trace amounts of C3 convertase, this allows the convertase to activate the added serum C3 in the fluid phase. The autoantibody therefore reacts with an enzyme in the complement system without blocking its active site; but it blocks the site at which the normal inhibitors act to destroy the enzyme and limit its action. This autoantibody to activated complement is thus a sort of immuno-conglutinin. Although first described in patients with the linear dense deposit form of mesangio-capillary nephritis it has also been found in patients without renal disease, in particular patients with partial lipodystrophy.
The test is only indicated if the C3 concentration is below normal and the C4 is within the reference range. If positive in a patient with renal disease it strongly suggests mesangio-capillary nephritis. About two-thirds of patients with partial lipodystrophy have a low C3 and circulating C3 nephritic factor, and have an increased tendency to develope mesangio-capillary nephritis.
The test should also be requested in any patient with an unexplained, isolated, low C3.
Sample requirement: 2 mL serum
Centres offering this assay:
London St George’s Hospital PRU Diagnostic Service
Sheffield Northern General’s PRU Diagnostic Service