Abstract
BackgroundComplement activation plays an important pathogenic role in numerous diseases. The ratio between an activation product and its parent protein is suggested to be more sensitive to detect complement activation than the activation product itself. In the present study we explored whether the ratio between the activation product and the parent protein for C3 (C3bc/C3) and for C5 (sC5b-9/C5) increased the sensitivity to detect complement activation in acute clinical settings compared to the activation product alone. Materials and methodsSamples from patients with acute heart failure following ST-elevated myocardial infarction (STEMI) and from patients with out-of-hospital cardiac arrest (OHCA) were used. C3, C3bc and C5, sC5b-9 were analysed in 629 and 672 patient samples, respectively. Healthy controls (n = 20) served to determine reference cut-off values for activation products and ratios, defined as two SD above the mean. ResultsIncreased C3bc/C3- and sC5b-9/C5 ratios were vastly dependent on C3bc and sC5b-9. Thus, 99.5 % and 98.1 % of the increased C3bc/C3- and sC5b-9/C5 ratios were solely dependent on increased C3bc and sC5b-9, respectively. Significantly decreased C3 and C5 caused increased ratios in only 3/600 (0.5 %) and 4/319 (1.3 %) samples, respectively. Strong correlations between C3bc and C3bc/C3-ratio and between sC5b-9 and sC5b-9/C5-ratio were found in the STEMI- (r = 0.926 and r = 0.786, respectively) and the OHCA-population (r = 0.908 and r = 0.843, respectively; p < 0.0001 for all). Importantly, sC5b-9 identified worse outcome groups better than sC5b-9/C5-ratio. ConclusionC3bc and sC5b-9 were sensitive markers of complement activation. The ratios of C3bc/C3 and sC5b-9/C5 did not improve detection of complement activation systemically.
Highlights
The human complement system is a rapid and efficient immune surveillance system that protects the host and preserves homeostasis
Through pattern recognition proteins (PRP), the complement system provides an instant protection against exogenous threats, such as foreign intruders and organisms, or endogenous danger evoked by altered host cells and damaged self (Ricklin et al, 2010)
The mean values with 95 % CI for Complement protein 3 (C3), C3bc, Complement protein 5 (C5), sC5b9 and the calculated ratios C3bc/C3 and sC5b-9/C5 are shown for the ST-elevated myocardial infarc tion (STEMI) and of-hospital cardiac arrest (OHCA) patients, respectively (Fig. 1)
Summary
The human complement system is a rapid and efficient immune surveillance system that protects the host and preserves homeostasis. Complement is suggested to play a key role in numerous other disease entities, where off-label use of eculizu mab has been provided (Ricklin et al, 2017). This is an interesting development and challenging, requiring solid complement-diagnostic tools and methods. The ratio between an activation product and its parent protein is suggested to be more sensitive to detect complement activation than the activation product itself. In the present study we explored whether the ratio between the activation product and the parent protein for C3 (C3bc/C3) and for C5 (sC5b-9/C5) increased the sensitivity to detect complement activation in acute clinical settings compared to the activation product alone. The ratios of C3bc/C3 and sC5b9/C5 did not improve detection of complement activation systemically
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
