PB0897 - Targeted proteomics in antiphospholipid syndrome: a case-control study

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Dagmar JM van Mourik, MSc

PhD student
Department of Thrombosis & Hemostasis, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands

Co-Author(s)

BV

Britte F. Van Der Vliet

MSc student
Department of Thrombosis & Hemostasis, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
LR

L. Renee Ruhaak

PhD, Associate professor
Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden
Leiden, Zuid-Holland, Netherlands
ND

Natasja Dolezal

Research technician
Department of Immunology, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
JD

Jan Wouter Drijfhout

PhD, Associate professor
Department of Immunology, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
RC

Robert A Cordfunke

Research technician
Department of Immunology, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
Saskia Middeldorp, MD, PhD

Internist, Professor
Radboud university medical center
Nijmegen, Gelderland, Netherlands
Jeroen Eikenboom

MD, PhD, prof
Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
Bv

Bart JM van Vlijmen

PhD, associate professor
Department of Thrombosis & Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
Tv

Thijs E. van Mens

MD, PhD
Department of Medicine - Thrombosis & Hemostasis, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands

Background: Antiphospholipid syndrome (APS) is a thrombotic autoimmune disease caused by a persistent presence of antibodies targeting phospholipids and phospholipid-binding proteins. A range of mechanisms have been implicated in the thrombotic and obstetric manifestations of APS. It is unclear which processes are dominant in vivo, although all mechanisms take place in the circulation. Exploring the plasma proteome may pinpoint dominant mechanisms or provide leads for further research.

Aims: To assess the abundance of plasma proteins of APS patients compared to healthy controls.

Methods: 61 APS patients without recent thrombotic or obstetric events and 19 healthy controls were included. Liquid chromatography-mass spectrometry was used to measure a panel of 162 plasma proteins, comprising inflammatory markers, apolipoproteins, complement, coagulation, and fibrinolytic proteins. These were quantified relative to stable isotope labeled internal standard proteins. Data were analyzed using a Welch’s t-test with false discovery rate multiple testing correction.

Results: A volcano plot indicates the plasma protein profiles of APS patients and healthy controls (Figure). Vitamin K dependent proteins were the only significant different proteins between APS patients and healthy controls due to vitamin K antagonist (VKA) use in the APS population. A subgroup analysis with stratifications for thrombotic or obstetric APS patients, also showed no difference in protein profiles.

Conclusion(s): We found no distinction between APS patients, without recent thrombotic or obstetric event, and healthy controls plasma protein profiles when corrected for VKA use. Plasma concentrations of the targeted proteins thus do not seem helpful in furthering the understanding of APS pathophysiology. This liquid-chromatography-mass spectrometry panel is a novel approach able to reliably quantify plasma proteins, as evidenced by the vitamin K dependent proteins, revealing the possibilities of this targeted analysis.