Complement deposition, C4d, on platelets is associated with vascular events in systemic lupus erythematosus

Author:

Svenungsson Elisabet1ORCID,Gustafsson Johanna T1,Grosso Giorgia1,Rossides Marios2ORCID,Gunnarsson Iva1,Jensen-Urstad Kerstin3,Larsson Anders4,Ekdahl Kristina N56,Nilsson Bo5,Bengtsson Anders A7,Lood Christian8

Affiliation:

1. Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm

2. Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm

3. Department of Clinical Physiology, Karolinska Institutet, Södersjukhuset, Stockholm

4. Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala

5. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala

6. Linnaeus Center of Biomaterials Chemistry, Linnaeus University, Kalmar

7. Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Lund, Sweden

8. Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA

Abstract

AbstractObjectiveComplement components, including C4d, can be found on activated platelets, a process associated with vascular disease in SLE. We investigated whether platelet C4d (PC4d) adds additional value to traditional and known lupus-associated risk factors when identifying SLE patients with vascular disease.MethodsThis cross-sectional study included 308 well-characterized SLE patients and 308 matched general population controls. PC4d deposition was analysed using flow cytometry. Values >95% of controls were considered as PC4d positive (+). aPL were determined by Luminex, and the LA test was performed by DRVVT. History of vascular disease (composite and as separate outcomes) was defined at inclusion.ResultsSLE patients had increased PC4d deposition as compared with population controls (50 vs 5%, P < 0.0001). PC4d+ positively associated with any vascular events, and separately with venous and cerebrovascular events, and also with all investigated aPL profiles. The association for any vascular event remained statistically significant after adjustment for traditional and SLE-associated risk factors (odds ratio: 2.3, 95% CI: 1.3, 4.3, P = 0.008). Compared with patients negative for both PC4d and LA, patients with double positivity were more likely to have vascular disease (odds ratio: 12.3, 95% CI: 5.4, 29.3; attributable proportion due to interaction 0.8, 95% CI: 0.4, 1.1)ConclusionPC4d+ is associated with vascular events in SLE, independently of traditional and SLE-associated risk factors. Concurrent presence of PC4d and LA seem to interact to further increase the odds for vascular events. Prospective studies should examine whether the aPL/PC4d combination can improve prediction of vascular events in SLE and/or APS.

Funder

The King Gustaf V 80th Birthday Fund

Swedish Research Council

Swedish Heart-Lung Foundation

Stockholm County Council

Swedish Rheumatism Association

Swedish Society for Medicine and Ingegerd Johansson’s Foundation

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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2. Complement and systemic lupus erythematosus;Dubois' Lupus Erythematosus and Related Syndromes;2025

3. Flow Cytometry and Platelets;Clinics in Laboratory Medicine;2024-09

4. Can complement activation be the missing link in antiphospholipid syndrome?;Rheumatology;2024-03-14

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