The Clinical Diagnostics Service of the Molecular Otolaryngology & Renal Research Laboratories is a CLIA-approved, Joint Commission-accredited diagnostic laboratory.
C3 Nephritic Factor/C5 Nephritic Factor/Nef Activity Assay
Dense Deposit Disease (DDD, aka Membranoproliferative Glomerulonephritis Type II, MPGNII)
C3 nephritic factors (C3Nefs), C5 nephritic factors (C5Nefs) and nephritic factor activity (nef activity) are defined as IgG autoantibodies to C3 convertase (C3bBb) that were first described by Spitzer and colleagues in 1969 as a substance in patient serum that constantly activated the alternative pathway cascade (Spitzer, 1969). They can be detected in ~80% of DDD patients and interfere with innate mechanisms that would otherwise control C3 convertase activity. Nephritic factors can also be detected in patients with partial lipodystrophy, meningococcal meningitis and post-streptococcal acute glomerulonephritis (Savage et al., 2009; Fremeaux-Bacchi, et al., 1994; Hulton, et al., 1992).
Indications for screening
Screening is appropriate for patients with biopsy-proven DDD.
MORL screening methodology
Three different methods are used to detect Nephritic Factors.
- Nef Activity Assay - Immunofixation electrophoresis (IFE) combines the techniques of electrophoresis with immunofixation to detect C3 degradation products, an indirect measure of dysregulation of C3 convertase. Conversion of C3 to C3c is quantitated (Koch, et al., 1981).
- C3Nef - C3 Convertase Stabilizing Assay (C3CSA) measures the ability of C3Nefs to stabilize C3 convertase on sheep erythrocytes. Stabilizing activities are reported as a function of hemolysis at 20 minutes.
- C5Nef - C3 Convertase Stabilizing Assay with Properdin (C3CSAP) measures the ability of C3Nefs to stabilize C3 convertase built with properdin on sheep erythrocytes. Stabilizing activities are reported as a function of hemolysis at 40 minutes.
Turnaround time is ~4 weeks
1 ml frozen serum (please see testing requisition for specimen handling).
Cost & CPT Codes
See the MORL testing Menu
Fremeaux-Bacchi, V, et al.: Hypocomplementaemia of poststreptococcal acute glomerulonephritis is associated with C3 nephritic factor (C3NeF) IgG autoantibody activity. Nephrol Dial Trans. 1995; 10(9); 1782-3.
PubMed ID: 7708258
Hulton, SA, et al.: Mesangiocapillary glomerulonephritis associated with meningococcal meningitis, C3 nephritic factor and persistently low complement C3 and C5. Pediatr Nephrol. 1992 May; 6(3):239-43.
PubMed ID: 1616831