OC 79.4 - High plasma C5a and C5b-9 levels during quiescent phases are associated with severe antiphospholipid syndrome subsets

Wednesday, June 26, 2024

11:00 – 11:15 ICT

Room: 209 A-D

Presenting Author(s)

Ariela Hoxha, PhD, MSc

Assistant Professor
Internal Medicine Unit, Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, University of Padua
Padua, Veneto, Italy

Co-Author(s)

AR

Amelia Ruffatti

Professor of Rheumatology
Department of Medicine, University of Padua
Padua, Veneto, Italy
MT

Marta Tonello

Biologist
Rheumatology Unit, Department of Medicine, University of Padua
Padua, Veneto, Italy
AC

Antonia Calligaro

Consultant
Rheumatology Unit, Department of Medicine, University of Padua
Padua, Veneto, Italy
Td

Teresa del Ross

Consultant
Rheumatology Unit, Department of Medicine, University of Padua
Padua, Veneto, Italy
MF

Maria Favaro

Consultant
Rheumatology Unit, Department of Medicine, University of Padua
Padua, Veneto, Italy
MZ

Margherita Zen

Associate Professor
Rheumatology Unit, Department of Medicine, University of Padua
Padua, Veneto, Italy
ML

Marco Lovisotto

Resident
Internal Medicine Unit, Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, University of Padua
Padua, Veneto, Italy
AD

Andrea Doria

Head of Rheumatology Unit
Rheumatology Unit, Department of Medicine, University of Padua
Padua, Veneto, Italy
Paolo Simioni, MD, PhD

Head of Department of Medicine
University of Padova, Padova University Hospital
Padova, Veneto, Italy

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.

Aims: 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).

Conclusion(s): 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.