Complement Bb Fragment Level Assay.

The activation of alternative pathway (AP) of complement generates the active proteolytic enzyme Bb. In the presence of C3b, factor B (MW: 93 kDa) binds to C3b to form the pre-convertase (C3bB). Factor D cleaves factor B releasing Ba (MW: 33 kDa) and generating the active proteolytic enzyme Bb (MW: 66kDa). The Bb subunit is catalytically active and cleaves new C3 to C3a and C3b. C3bBb recruits additional available C3b to form the C5 convertase, C3bBbC3b, launching terminal pathway activation. C3 convertase can be dissociated by spontaneous decay or complement regulators (factor H, CR1). It can also be inactivated by factor I-mediated C3b cleavage in presence of cofactors.

The common pathophysiological basis of both Dense Deposit Disease (DDD) and C3 Glomerulonephritis (C3GN) is dysregulation of the AP. Consumption of AP complement components is dependent on the degree of dysregulation of the C3 and C5 convertases. Plasma levels of Bb are elevated in both DDD and C3GN as compared to controls (p<0.001) consistent with dysregulation of the C3 convertase in both diseases (see Zhang et al. Defining the complement biomarker profile of C3 glomerulopathy, CJASN 2014).

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

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

Turnaround time
Turnaround time is ~2 weeks

Sample Required 
1 ml frozen EDTA plasma (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.