Soluble C5b-9 (sC5b-9) in Pediatrics-A Clinical Assessment.

Abstract

Background: The soluble C5b-9 (sC5b-9) is a soluble form of the Terminal Complement Complex (TCC) that is released into the circulation with elevated levels, associated with increased morbidity and mortality in patients with complement-mediated inflammatory conditions. With the advent of eculizumab and ravulizumab, proper testing for diagnoses and therapeutic monitoring is warranted.

Methods: We evaluated both the analytical and clinical performance of the Quidel Microvue sC5b-9 Plus enzyme immunoassay. Analytical performance was evaluated with precision, linearity, interference studies, and correlation with a reference laboratory. Reference intervals were established using control donor samples [n = 26; median age 18.5 years (range 2-59)]. Clinical performance of the assay was assessed using plasma samples of patients who (i) developed transplant-associated thrombotic microangiopathy [n = 10; median age 14 years (range 3-19)], (ii) had reduced ADAMTS13 activity [n = 6; median age 16 years (range 9-18)], and (iii) developed acquired Von-Willebrand disease [n = 10; median age 18.5 years (range 0.5-18)].

Results: The assay showed acceptable intra and inter-precision at both low and high levels. Linearity ranged from 12.6 to 160.66 ng/mL, while accuracy and method correlation studies with a reference laboratory yielded a correlation coefficient (R) of 0.96. The reference range in control donors was established at ≤ 268.0 ng/mL. Clinical performance of the assay in patients' plasma revealed elevated sC5b-9 levels suggesting complement activation in these patient cohorts compared with control levels.

Conclusion: The Quidel Microvue sC5b-9 plus EIA assay demonstrated acceptable analytical performance and clinical utility for monitoring complement activation in patients. Further studies are needed to correlate sC5b-9 levels with existing markers of complement activation.