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Platelet Activation and Anti-Phospholipid Antibodies Collaborate in the Activation of the Complement System on Platelets in Systemic Lupus Erythematosus

Anti-phospholipid (aPL) antibodies are important contributors to development of thrombosis in patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE). The underlying mechanism of aPL antibody-mediated thrombosis is not fully understood but existing data suggest that platele...

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Autores principales: Lood, Christian, Tydén, Helena, Gullstrand, Birgitta, Sturfelt, Gunnar, Jönsen, Andreas, Truedsson, Lennart, Bengtsson, Anders A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055750/
https://www.ncbi.nlm.nih.gov/pubmed/24922069
http://dx.doi.org/10.1371/journal.pone.0099386
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author Lood, Christian
Tydén, Helena
Gullstrand, Birgitta
Sturfelt, Gunnar
Jönsen, Andreas
Truedsson, Lennart
Bengtsson, Anders A.
author_facet Lood, Christian
Tydén, Helena
Gullstrand, Birgitta
Sturfelt, Gunnar
Jönsen, Andreas
Truedsson, Lennart
Bengtsson, Anders A.
author_sort Lood, Christian
collection PubMed
description Anti-phospholipid (aPL) antibodies are important contributors to development of thrombosis in patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE). The underlying mechanism of aPL antibody-mediated thrombosis is not fully understood but existing data suggest that platelets and the complement system are key components. Complement activation on platelets is seen in SLE patients, especially in patients with aPL antibodies, and has been related to venous thrombosis and stroke. The aim of this study was to investigate if aPL antibodies could support classical pathway activation on platelets in vitro as well as in SLE patients. Furthermore, we investigated if complement deposition on platelets was associated with vascular events, either arterial or venous, when the data had been adjusted for traditional cardiovascular risk factors. Finally, we analyzed if platelet complement deposition, both C1q and C4d, was specific for SLE. We found that aPL antibodies supported C4d deposition on platelets in vitro as well as in SLE patients (p = 0.001 and p<0.05, respectively). Complement deposition on platelets was increased in SLE patients when compared with healthy individuals (p<0.0001). However, high levels of C4d deposition and a pronounced C1q deposition were also seen in patients with rheumatoid arthritis and systemic sclerosis. In SLE, C4d deposition on platelets was associated with platelet activation, complement consumption, disease activity and venous (OR = 5.3, p = 0.02), but not arterial, thrombosis, observations which were independent of traditional cardiovascular risk factors. In conclusion, several mechanisms operate in SLE to amplify platelet complement deposition, of which aPL antibodies and platelet activation were identified as important contributors in this investigation. Complement deposition on platelets was identified as a marker of venous, but not arterial thrombosis, in SLE patients independently of traditional risk factors and aPL antibodies. Further studies are needed to elucidate the role of complement deposition on platelets in development of venous thrombosis.
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spelling pubmed-40557502014-06-18 Platelet Activation and Anti-Phospholipid Antibodies Collaborate in the Activation of the Complement System on Platelets in Systemic Lupus Erythematosus Lood, Christian Tydén, Helena Gullstrand, Birgitta Sturfelt, Gunnar Jönsen, Andreas Truedsson, Lennart Bengtsson, Anders A. PLoS One Research Article Anti-phospholipid (aPL) antibodies are important contributors to development of thrombosis in patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE). The underlying mechanism of aPL antibody-mediated thrombosis is not fully understood but existing data suggest that platelets and the complement system are key components. Complement activation on platelets is seen in SLE patients, especially in patients with aPL antibodies, and has been related to venous thrombosis and stroke. The aim of this study was to investigate if aPL antibodies could support classical pathway activation on platelets in vitro as well as in SLE patients. Furthermore, we investigated if complement deposition on platelets was associated with vascular events, either arterial or venous, when the data had been adjusted for traditional cardiovascular risk factors. Finally, we analyzed if platelet complement deposition, both C1q and C4d, was specific for SLE. We found that aPL antibodies supported C4d deposition on platelets in vitro as well as in SLE patients (p = 0.001 and p<0.05, respectively). Complement deposition on platelets was increased in SLE patients when compared with healthy individuals (p<0.0001). However, high levels of C4d deposition and a pronounced C1q deposition were also seen in patients with rheumatoid arthritis and systemic sclerosis. In SLE, C4d deposition on platelets was associated with platelet activation, complement consumption, disease activity and venous (OR = 5.3, p = 0.02), but not arterial, thrombosis, observations which were independent of traditional cardiovascular risk factors. In conclusion, several mechanisms operate in SLE to amplify platelet complement deposition, of which aPL antibodies and platelet activation were identified as important contributors in this investigation. Complement deposition on platelets was identified as a marker of venous, but not arterial thrombosis, in SLE patients independently of traditional risk factors and aPL antibodies. Further studies are needed to elucidate the role of complement deposition on platelets in development of venous thrombosis. Public Library of Science 2014-06-12 /pmc/articles/PMC4055750/ /pubmed/24922069 http://dx.doi.org/10.1371/journal.pone.0099386 Text en © 2014 Lood et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lood, Christian
Tydén, Helena
Gullstrand, Birgitta
Sturfelt, Gunnar
Jönsen, Andreas
Truedsson, Lennart
Bengtsson, Anders A.
Platelet Activation and Anti-Phospholipid Antibodies Collaborate in the Activation of the Complement System on Platelets in Systemic Lupus Erythematosus
title Platelet Activation and Anti-Phospholipid Antibodies Collaborate in the Activation of the Complement System on Platelets in Systemic Lupus Erythematosus
title_full Platelet Activation and Anti-Phospholipid Antibodies Collaborate in the Activation of the Complement System on Platelets in Systemic Lupus Erythematosus
title_fullStr Platelet Activation and Anti-Phospholipid Antibodies Collaborate in the Activation of the Complement System on Platelets in Systemic Lupus Erythematosus
title_full_unstemmed Platelet Activation and Anti-Phospholipid Antibodies Collaborate in the Activation of the Complement System on Platelets in Systemic Lupus Erythematosus
title_short Platelet Activation and Anti-Phospholipid Antibodies Collaborate in the Activation of the Complement System on Platelets in Systemic Lupus Erythematosus
title_sort platelet activation and anti-phospholipid antibodies collaborate in the activation of the complement system on platelets in systemic lupus erythematosus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055750/
https://www.ncbi.nlm.nih.gov/pubmed/24922069
http://dx.doi.org/10.1371/journal.pone.0099386
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