Contact activation products are new potential biomarkers to evaluate the risk of thrombotic events in systemic lupus erythematosus

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Contact activation products are new potential biomarkers to evaluate the risk of thrombotic events in systemic lupus erythematosus

Bäck, Jennie (författare): Uppsala universitet,Institutionen för immunologi, genetik och patologi,Bo NiIsson,Uppsala University

Lood, Christian (författare): Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital

Bengtsson, Anders A. (författare): Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Skåne University Hospital

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Nilsson Ekdahl, Kristina (författare): Linnaeus University,Uppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University,Linnaeus Ctr Biomat Chem, BMC,Institutionen för immunologi, genetik och patologi,Bo Nilsson

Nilsson, Bo (författare): Uppsala universitet,Institutionen för immunologi, genetik och patologi,Bo Nilsson,Uppsala University

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Springer Science and Business Media LLC, 2013
2013
Engelska.
Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 15:6

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://arthritis-re...; https://uu.diva-port... (primary) (Raw object); http://dx.doi.org/10... (free); https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; https://lup.lub.lu.s...; visa färre...

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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.

Ämnesord

NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

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Biomedicinsk vetenskap
Biomedical Sciences

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Av författaren/redakt...: Bäck, Jennie; Lood, Christian; Bengtsson, Ander ...; Nilsson Ekdahl, ...; Nilsson, Bo

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NATURVETENSKAP: NATURVETENSKAP; och Biologi; och Immunologi

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Reumatologi och ...

Artiklar i publikationen: Arthritis Resear ...

Av lärosätet: Linnéuniversitetet; Uppsala universitet; Lunds universitet

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