OP0240 HIGH PLASMA C5a AND C5b-9 LEVELS DURING QUIESCENT PHASES ARE ASSOCIATED WITH SEVERE ANTIPHOSPHOLIPID SYNDROME SUBSETS

Background: Complement activation has recently emerged, implicated in the pathogenesis of antiphospholipid syndrome (APS)-related clinical events. High plasma C5a and C5b-9 levels are considered a sign of complement activation. Objectives: To evaluate the association of C5a and C5b-9 plasma levels with different clinical and laboratory APS subsets. Methods: We conducted a monocentric exploratory cross-sectional study. Plasmas of 62 quiescent APS patients [40 with thrombosis responsive to vitamin K antagonists (VKA) therapy (TAPS), 13 with refractory to VKA recurrent thrombosis (RAPS), 9 with CAPS], 13 active APS(2 TAPS, 7 RAPS, and 4 CAPS), and 30 sex and age-matched healthy controls (HC) were recruited. Plasma concentrations of C5a and C5b-9 were assessed using commercial ELISA assays. Results: The C5b-9 levels in quiescent CAPS were significantly higher than in TAPS [median, 330.2 ng/mL (IQR, 86.6); vs 189.7 ng/mL (IQR, 138.9) and in HC [median, 330.2 ng/mL (IQR, 86.6) vs 120.9 ng/mL (IQR, 83.7)]. Similarly, the C5a levels were significantly higher in CAPS than in TAPS [median, 27.6 ng/mL (IQR, 58.4) vs. 8.9 ng/mL (IQR, 8.3) and the HC [median, 27.6 ng/mL (IQR, 58.4) vs. 4.9 ng/mL (IQR, 4.9)]. Moreover, both C5a and/or C5b-9 were significantly higher in RAPS than in TAPS [median 15.6 ng/mL (IQR, 51.8) vs. 11.6 ng/mL (IQR, 9.3) and median 814.6 ng/mL (IQR, 2808.4) vs. 309.6 (291.7)]. In addition, C5a and/or C5b-9 significantly prevailed in the patients with active APS vs. Quiescent APS [median 41.2 ng/mL (IQR, 67.3) vs. 14.3 ng/mL (IQR, 8.3) and median 1691.0 ng/mL (IQR,1788.3) vs. 448.9 ng/mL (IQR, 463.6)] as well as in the small-vessel thrombosis (p=0.0088), just as C5b-9 did in the triple antiphospholipid antibody-positive patients (p=0.0248). The ROC curve showed that the best cut-offs for C5a and C5b-9 levels had a higher sensitivity, specificity, and likelihood ratio in the CAPS and RAPS groups than in the TAPS subset. Conclusion: High plasma C5b-9 and C5a levels during quiescent phases identify APS patients with more severe disease who may develop recurrent thrombosis and benefit from complement inhibition treatment during an acute disease phase. REFERENCES: [1] Chaturvedi S, Braunstein EM, Yuan X, Yu J, Alexander A, Chen H, Gavriilaki E, Alluri R, Streiff MB, Petri M, Crowther MA, McCrae KR, Brodsky RA. Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS. Blood. 2020 Jan 23;135(4):239-251. doi:10.1182/blood.2019003863. Acknowledgements: NIL. Disclosure of Interests: None declared.