Complement C3 Level

Complement C3 (MW: 183 kDa) is one of the most abundant plasma proteins. It is a pivotal component of complement and is central to the activation cascades. The mature protein is composed of two disulfide-bound polypeptide chains (C3α and C3β). The three complement activation pathways (alternative, classical, lectin) converge at the stage of C3 cleavage to generate the activated form of C3, which is C3b. C3b generates new C3 convertases by interacting with factors B, D and properdin. In the presence of abundant C3b, C5 convertases are formed.

Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are two ultra-rare renal diseases characterized by fluid-phase dysregulation of C3 and C5 convertases that can lead to partial or complete consumption of circulating complement components, including C3. Consumption of C3 is consistent with activation of the alternative pathway of complement (see Zhang et al. Defining the complement biomarker profile of C3 glomerulopathy, CJASN 2014).

C3 levels are also reduced in 30% to 50% of patients with atypical hemolytic uremic syndrome (aHUS) carrying Factor H mutations, and 20% to 30% of patients carrying Factor I mutations, a finding consistent with complement-dependent disease (Loirat & Frémeaux-Bacchi, 2011). Concentrations of factors H and I can clarify the mechanism of C3 consumption. In ~60% of aHUS patients, C3, Factor B, Factor H and Factor I levels are normal. In these patients, the type of complement-associated defect cannot be predicted by measuring plasma protein levels but may be discoverable by genetic analysis.

Indications for screening
Screening is appropriate in patients with complement-mediated renal diseases

MORL screening methodology
Turbidimetry-based method

Turnaround time
Turnaround time is ~2 weeks

Sample Required
1 ml frozen serum (Red top, see testing requisition (page 3) for specimen handling).

Cost & CPT Codes

The Clinical Diagnostics Service of the Molecular Otolaryngology & Renal Research Laboratories is a CLIA-approved, Joint Commission-accredited diagnostic laboratory.