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; Søren Risom Kristensen; Mogens T Stender; Ole Thorlacius-Ussing; Irene Martínez-Martínez; Vicente Vasquez; Javier Corral

doi:10.1160/TH10-05-0297

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, Søren Risom Kristensen, Mogens T Stender, Ole Thorlacius-Ussing, Irene Martínez-Martínez, Vicente Vasquez, Javier Corral

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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.

Original language	English
Journal	Thrombosis and Haemostasis
Volume	104
Issue	6
Pages (from-to)	1143-9
Number of pages	7
ISSN	0340-6245
DOIs	https://doi.org/10.1160/TH10-05-0297
Publication status	Published - 1 Dec 2010

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Ordóñez, A., Yélamos, J., Pedersen, S., Miñano, A., Conesa-Zamora, P., Kristensen, S. R., Stender, M. T., Thorlacius-Ussing, O., Martínez-Martínez, I., Vasquez, V., & Corral, J. (2010). 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. Thrombosis and Haemostasis, 104(6), 1143-9. https://doi.org/10.1160/TH10-05-0297

@article{e443b2007c5a4591832af210613cf088,

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.",

author = "Adriana Ord{\'o}{\~n}ez and Jose Y{\'e}lamos and Shona Pedersen and Antonia Mi{\~n}ano and Pablo Conesa-Zamora and Kristensen, {S{\o}ren Risom} and Stender, {Mogens T} and Ole Thorlacius-Ussing and Irene Mart{\'i}nez-Mart{\'i}nez and Vicente Vasquez and Javier Corral",

year = "2010",

month = dec,

day = "1",

doi = "10.1160/TH10-05-0297",

language = "English",

volume = "104",

pages = "1143--9",

journal = "Thrombosis and Haemostasis",

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Ordóñez, A, Yélamos, J, Pedersen, S, Miñano, A, Conesa-Zamora, P, Kristensen, SR, Stender, MT, Thorlacius-Ussing, O, Martínez-Martínez, I, Vasquez, V & Corral, J 2010, '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', Thrombosis and Haemostasis, vol. 104, no. 6, pp. 1143-9. https://doi.org/10.1160/TH10-05-0297

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. / Ordóñez, Adriana; Yélamos, Jose; Pedersen, Shona et al.
In: Thrombosis and Haemostasis, Vol. 104, No. 6, 01.12.2010, p. 1143-9.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - 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

AU - Ordóñez, Adriana

AU - Yélamos, Jose

AU - Pedersen, Shona

AU - Miñano, Antonia

AU - Conesa-Zamora, Pablo

AU - Kristensen, Søren Risom

AU - Stender, Mogens T

AU - Thorlacius-Ussing, Ole

AU - Martínez-Martínez, Irene

AU - Vasquez, Vicente

AU - Corral, Javier

PY - 2010/12/1

Y1 - 2010/12/1

N2 - 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.

AB - 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.

U2 - 10.1160/TH10-05-0297

DO - 10.1160/TH10-05-0297

M3 - Journal article

C2 - 20838745

SN - 0340-6245

VL - 104

SP - 1143

EP - 1149

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

IS - 6

ER -

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

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