Contact activation products are new potential biomarkers to evaluate the risk of thrombotic events in systemic lupus erythematosus
(2013) In Arthritis Research and Therapy 15(6). p.1-10- Abstract
Introduction: Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE.Methods: Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact... (More)
Introduction: Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE.Methods: Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters.Results: Fibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT.Conclusions: Activation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.
(Less)
- author
- Bäck, Jennie ; Lood, Christian LU ; Bengtsson, Anders A. LU ; Ekdahl, Kristina N. and Nilsson, Bo
- organization
- publishing date
- 2013-12-04
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Arthritis Research and Therapy
- volume
- 15
- issue
- 6
- article number
- R206
- pages
- 1 - 10
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:24299152
- scopus:84888780786
- ISSN
- 1478-6354
- DOI
- 10.1186/ar4399
- language
- English
- LU publication?
- yes
- id
- c157d69f-2124-48dc-b514-3b14105f111e
- date added to LUP
- 2019-05-23 09:41:13
- date last changed
- 2025-04-16 19:27:44
@article{c157d69f-2124-48dc-b514-3b14105f111e,
abstract = {{<p>Introduction: Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE.Methods: Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters.Results: Fibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT.Conclusions: Activation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.</p>}},
author = {{Bäck, Jennie and Lood, Christian and Bengtsson, Anders A. and Ekdahl, Kristina N. and Nilsson, Bo}},
issn = {{1478-6354}},
language = {{eng}},
month = {{12}},
number = {{6}},
pages = {{1--10}},
publisher = {{BioMed Central (BMC)}},
series = {{Arthritis Research and Therapy}},
title = {{Contact activation products are new potential biomarkers to evaluate the risk of thrombotic events in systemic lupus erythematosus}},
url = {{http://dx.doi.org/10.1186/ar4399}},
doi = {{10.1186/ar4399}},
volume = {{15}},
year = {{2013}},
}