Increased levels of citrullinated antithrombin in plasma of patients with rheumatoid arthritis and colorectal adenocarcinoma determined by a newly developed ELISA using a specific monoclonal antibody

Adriana Ordóñez; Jose Yélamos; Shona Pedersen; Antonia Miñano; Pablo Conesa-Zamora; Soren R. Kristensen; Mogens T. Stender; Ole Thorlacius-Ussing; Irene Martínez-Martínez; Vicente Vicente; Javier Corral

doi:10.1160/TH10-05-0297

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(06): 1143-1149
DOI: 10.1160/TH10-05-0297

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Increased levels of citrullinated antithrombin in plasma of patients with rheumatoid arthritis and colorectal adenocarcinoma determined by a newly developed ELISA using a specific monoclonal antibody

Authors

Adriana Ordóñez

¹Centro Regional de Hemodonación, University of Murcia, Spain
Jose Yélamos

²Department of Immunology, Cancer Program, IMIM-Hospital del Mar, Barcelona, Spain
Shona Pedersen

³Aarhus University Hospital, Aalborg Hospital, Clinical Biochemistry, Centre for Cardiovascular Research, Aalborg, Denmark
Antonia Miñano

¹Centro Regional de Hemodonación, University of Murcia, Spain
Pablo Conesa-Zamora

⁴Grupo de Patología Molecular y Farmacogenética, Hospital Universitario Santa María del Rosell, Cartagena, Spain
Soren R. Kristensen

³Aarhus University Hospital, Aalborg Hospital, Clinical Biochemistry, Centre for Cardiovascular Research, Aalborg, Denmark
Mogens T. Stender

⁵Aalborg Hospital, Aarhus University Hospital, Department of Surgical Gastroenterology, Aalborg, Jutland, Denmark
Ole Thorlacius-Ussing

⁵Aalborg Hospital, Aarhus University Hospital, Department of Surgical Gastroenterology, Aalborg, Jutland, Denmark
Irene Martínez-Martínez

¹Centro Regional de Hemodonación, University of Murcia, Spain
Vicente Vicente

¹Centro Regional de Hemodonación, University of Murcia, Spain
Javier Corral

¹Centro Regional de Hemodonación, University of Murcia, Spain

Abstract

Summary

Citrullination is a post-translational modification that plays essential roles in both physiological processes and disease. Recent studies have found increased levels of citrullinated antithrombin in patients with rheumatoid arthritis and in different malignant tumours. Antithrombin, the main haemostatic serpin, loses its anticoagulant function via citrullination, which might contribute to the pathogenesis or thrombotic side effects of these disorders. We have developed a specific monoclonal antibody against citrullinated antithrombin. We determined the levels of citrullinated antithrombin and anti-FXa activity in plasma from 66 donors, 17 patients with rheumatoid arthritis and 77 patients with colorectal adenocarcinoma (42 suffering from venous thrombosis). Healthy subjects had negligible amounts of citrullinated antithrombin in plasma (7.9 ± 22.1 ng/ml), while it significantly increased in patients with rheumatoid arthritis or adenocarcinoma (159.7 ± 237.6 ng/ml and 36.8 ± 66.1 ng/ml), levels that, however, did not modify the plasma anticoagulant activity. Moreover, we did not find association between citrullinated antithrombin and the thrombotic risk in patients with adenocarcinoma. In conclusion, we have developed an antibody specific for citrullinated antithrombin that allows its quantification in biological samples, offering a new tool for the analysis of citrullination in different diseases. We confirm increased levels of citrullinated antithrombin in plasma of patients with rheumatoid arthritis and adenocarcinoma. This modification, probably local, could have pathological consequences in both disorders, but only affects a minor fraction of plasma antithrombin, resulting in no significant reduction of global anticoagulant activity. This result explains the absence of association of this marker with an increased risk of thrombosis in patients with colorectal adenocarcinoma.

Keywords

Antithrombin - citrullination - monoclonal antibody - rheumatoid arthritis - cancer

Full Text

References

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