title: 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.
abstract: 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.
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ordóñez
authors.forename: Jose
authors.initials: J
authors.lastname: Yélamos
authors.forename: Shona
authors.initials: S
authors.lastname: Pedersen
authors.forename: Antonia
authors.initials: A
authors.lastname: Miñano
authors.forename: Pablo
authors.initials: P
authors.lastname: Conesa-Zamora
authors.forename: Soren R
authors.initials: SR
authors.lastname: Kristensen
authors.forename: Mogens T
authors.initials: MT
authors.lastname: Stender
authors.forename: Ole
authors.initials: O
authors.lastname: Thorlacius-Ussing
authors.forename: Irene
authors.initials: I
authors.lastname: Martínez-Martínez
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.forename: Javier
authors.initials: J
authors.lastname: Corral
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000150:complications; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D000918:Antibody Specificity; D000991:Antithrombins / Q000097:blood* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D002956:Citrulline / Q000097:blood* / Q000276:immunology; D015179:Colorectal Neoplasms / Q000097:blood* / Q000150:complications; D004797:Enzyme-Linked Immunosorbent Assay; D065427:Factor Xa Inhibitors; D006801:Humans; D011499:Protein Processing, Post-Translational; D015854:Up-Regulation; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology
chemical_list: D000911:Antibodies, Monoclonal; D000991:Antithrombins; D015415:Biomarkers; D065427:Factor Xa Inhibitors; D002956:Citrulline