Alternative Pathway Functional Assay (APFA)

The Alternative Pathway Functional Assay (APFA) measures activity of the alternative pathway (AP) of complement. Specific initiators are used to stimulate the AP on patient-derived sera; neoantigens of C9 produced as a result of terminal complement complex (C5b-9) activation are measured. Consumption or depleted of AP complement proteins will result in a low (abnormal) APFA.

Dense Deposit Disease, C3 Glomerulonephritis and atypical Hemolytic Uremic Syndrome
Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are two ultra-rare renal diseases. Both diseases are characterized by fluid-phase dysregulation of the AP that often leads to partial or complete consumption of circulating complement components, including complement C3, factor B, properdin and C5 (see Zhang et al. Defining the complement biomarker profile of C3 glomerulopathy, CJASN 2014). As a consequence, APFA can be low.

Indications for screening
Screening is appropriate for patients with dysregulated AP activity.

MORL screening methodology 
Modified Enzyme Linked Immuno-Sorbent Assay (ELISA)

Turnaround time
Turnaround time is ~2 weeks

Sample Required
1 ml frozen serum (see testing requisition 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.