Anti-protein C antibodies and acquired protein C resistance in SLE: novel markers for thromboembolic events and disease activity?

Author:

Ramirez Giuseppe A123ORCID,Mackie Ian4,Nallamilli Susanna45,Pires Tatiana126,Moll Rachel45,Pericleous Charis12,Isenberg David A12ORCID,Cohen Hannah45,Efthymiou Maria4

Affiliation:

1. Division of Medicine, Centre for Rheumatology, University College , London, UK

2. Department of Rheumatology, University College London Hospitals NHS Foundation Trust, London, UK

3. Università Vita-Salute San Raffaele, Milan, Italy

4. Department of Haematology, Haemostasis Research Unit, University College London, London, UK

5. Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK

6. Serviço de Medicina 1, Hospital de Santo André, Centro Hospitalar de Leiria, Leiria, Portugal

Abstract

Abstract Objectives Risk factors for thromboembolism in SLE are poorly understood. We hypothesized a possible role for protein C, based on its dual activity in inflammation and haemostasis and on the evidence of an association between acquired activated protein C (APC) resistance (APCR) and high-avidity anti-protein C antibodies (anti-PC) with a severe thrombotic phenotype in venous thrombosis APS patients. Methods In a cross-sectional study of 156 SLE patients, the presence and avidity of IgG anti-PC was established by in house-ELISA, and APCR to exogenous recombinant human APC (rhAPC) and Protac (which activates endogenous protein C) was assessed by thrombin generation-based assays. Associations with aPL profile, thrombotic history and disease activity (BILAG and SLEDAI-2K) were also established. Results Anti-PC were detected in 54.5% of patients and APCR in 59%. Anti-PC positivity was associated with APCR to both rhAPC (P <0.0001) and Protac (P =0.0001). High-avidity anti-PC, detected in 26.3% of SLE patients, were associated with APCR in patients with thrombosis only (P <0.05), and with the development of thrombosis over time (range: 0–52 years; P =0.014). High-avidity anti-PC levels correlated with SLEDAI-2K (P =0.033) and total BILAG (P =0.019); SLEDAI-2K correlated inversely with APCR to Protac (P =0.004). Conclusion Anti-PC occur in patients with SLE, independently of aPL profile, and are associated with APCR. High-avidity anti-PC are associated with thrombosis and with active disease and might prove a novel marker to monitor the risk of thrombosis and disease progression in SLE.

Funder

Rheumatology Discretionary Fund UCL Charity

Haematology UCLH Charity Fund

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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