MORL Screening Methodology

Turbidimetry-based method.

  • Serum samples must be frozen to below -80°C immediately after separation from cells and shipped on dry ice. These samples remain viable for at least six months when stored at -80°C.

  • All serum samples MUST be processed and frozen down to -80°C immediately after collection
  • Labeled with the sample type AND patient’s name, DOB, MRN and sex
  • Cryovials should be put in zip lock bags and completely covered in dry ice to keep the sample frozen until it arrives in the lab
  • Shipped overnight on at least 5 lbs of dry ice
  • Shipping and receiving dock closed on weekends and holidays 
    • Deliveries accepted Monday - Friday 

If samples arrive thawed they will be REJECTED.

 

Click here to print sample and shipping requirements.

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.

Information

Quick Facts

  • CPT code: 86160 
  • Test code: 07C3L
  • Turnaround time: 2 weeks
  • Cost: $110

Background Information

Complement C3 (MW: 184 kDa) is one of the most abundant plasma proteins and plays a pivotal role in the complement system.  It is the cornerstone of complement activation. The mature C3 protein has two disulfide-bound polypeptide chains, namely C3α and C3β. All three complement activation pathways—alternative, classical, and lectin—converge at the point of C3 cleavage to yield the activated form of C3 known as C3b. C3b fosters the generation of new C3 convertases through interactions with factors B, D, and properdin, ultimately leading to the formation of C5 convertases in the presence of abundant C3b. 

C3 levels are reduced in 30-50% of patients with atypical hemolytic uremic syndrome/complement-mediated TMA and in 20-30% of those with CFI gene mutations, consistent with complement-dependent disease (Loirat & Frémeaux-Bacchi, 2011). Concentrations of factors H and I can clarify the mechanism behind C3 consumption. Approximately 50% patients with atypical hemolytic uremic syndrome/complement-mediated TMA have normal levels of C3, factor B, factor H, and factor I. In such cases, the specific type of complement-associated defect cannot be predicted through plasma protein level measurements but may be identified through genetic analysis. C3 levels are often diminished or become undetectable in individuals with C3 glomerulopathy, primarily due to the presence of acquired disease-driving factors such as C3 nephritic factors. 

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