Dr. Atsumi has received consulting fees, speaking fees, and/or honoraria from Mitsubishi Tanabe, Takeda, Pfizer, Bristol-Myers Squibb, Chugai, Eisai, Abbott Japan, and MBL (less than $10,000 each).
Systemic Lupus Erythematosus
Novel assays of thrombogenic pathogenicity in the antiphospholipid syndrome based on the detection of molecular oxidative modification of the major autoantigen β2-glycoprotein I †
Version of Record online: 31 AUG 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 9, pages 2774–2782, September 2011
How to Cite
Ioannou, Y., Zhang, J.-Y., Qi, M., Gao, L., Qi, J. C., Yu, D.-M., Lau, H., Sturgess, A. D., Vlachoyiannopoulos, P. G., Moutsopoulos, H. M., Rahman, A., Pericleous, C., Atsumi, T., Koike, T., Heritier, S., Giannakopoulos, B. and Krilis, S. A. (2011), Novel assays of thrombogenic pathogenicity in the antiphospholipid syndrome based on the detection of molecular oxidative modification of the major autoantigen β2-glycoprotein I . Arthritis & Rheumatism, 63: 2774–2782. doi: 10.1002/art.30383
Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms
- Issue online: 31 AUG 2011
- Version of Record online: 31 AUG 2011
- Accepted manuscript online: 26 MAY 2011 01:45PM EST
- Manuscript Accepted: 29 MAR 2011
- Manuscript Received: 16 DEC 2010
- Arthritis Research UK (Clinician Scientist Fellowship award). Grant Number: 17821
- Tianjin Medical University, Tianjin, China
- Arthritis Research UK. Grant Number: 18491
- National Health and Medical Research Council of Australia
Beta-2-glycoprotein I (β2GPI) constitutes the major autoantigen in the antiphospholipid syndrome (APS), a common acquired cause of arterial and venous thrombosis. We recently described the novel observation that β2GPI may exist in healthy individuals in a free thiol (biochemically reduced) form. The present study was undertaken to quantify the levels of total, reduced, and posttranslationally modified oxidized β2GPI in APS patients compared to various control groups.
In a retrospective multicenter analysis, the proportion of β2GPI with free thiols in serum from healthy volunteers was quantified. Assays for measurement of reduced as well as total circulating β2GPI were developed and tested in the following groups: APS (with thrombosis) (n = 139), autoimmune disease with or without persistent antiphospholipid antibodies (aPL) but without APS (n = 188), vascular thrombosis without APS or aPL (n = 38), and healthy volunteers (n = 91).
Total β2GPI was significantly elevated in patients with APS (median 216.2 μg/ml [interquartile range 173.3–263.8]) as compared to healthy subjects (median 178.4 μg/ml [interquartile range 149.4–227.5] [P < 0.0002]) or control patients with autoimmune disease or vascular thrombosis (both P < 0.0001). The proportion of total β2GPI in an oxidized form (i.e., lacking free thiols) was significantly greater in the APS group than in each of the 3 control groups (all P < 0.0001).
This large retrospective multicenter study shows that posttranslational modification of β2GPI via thiol-exchange reactions is a highly specific phenomenon in the setting of APS thrombosis. Quantification of posttranslational modifications of β2GPI in conjunction with standard laboratory tests for APS may offer the potential to more accurately predict the risk of occurrence of a thrombotic event in the setting of APS.