The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study.
BACKGROUND
Diagnosis of the antiphospholipid syndrome (APS) is difficult as a result of limited specificity of existing assays for detecting clinically relevant antiphospholipid antibodies. Anti-beta2-glycoprotein I (beta 2GPI) antibodies play a central role in the disease process of APS.


OBJECTIVE
We have investigated the relation between antiphospholipid antibodies with specificity for domain I of beta 2GPI and thrombosis/pregnancy morbidity in an international multicenter study.


METHODS
Four hundred and seventy-seven patients derived from nine different centres met the inclusion criterion of having anti-beta 2GPI antibodies in their plasma/serum. Clinical data and results of tests for lupus anticoagulant, anti-cardiolipin antibodies and anti-beta 2GPI antibodies were established at the different centres of inclusion. After being re-tested for the presence of IgG and/or IgM anti-beta 2GPI antibodies, the samples were tested for the presence of IgG-directed against domain I of beta 2GPI and results were correlated with the thrombotic and obstetric history.


RESULTS
Re-testing for the presence of anti-beta 2GPI antibodies resulted in inclusion of 442/477 patients. IgG class anti-domain I antibodies were present in plasma of 243/442 patients (55%). 201/243 (83%) had a history of thrombosis. This resulted in an odds ratio of 3.5 (2.3-5.4, 95% confidence interval) for thrombosis. Anti-domain I IgG antibodies were also significantly correlated with obstetric complications [odds ratio: 2.4 (1.4-4.3, 95% confidence interval)].


CONCLUSIONS
In this multicenter study, the detection of IgG antibodies that are directed against domain I of beta 2GPI proved to be more strongly associated with thrombosis and obstetric complications than those detected using the standard anti-beta 2GPI antibody assay.
de Laat
B
B
Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands. b.delaat@sanquin.nl
Pengo
V
V
Pabinger
I
I
Musial
J
J
Voskuyl
A E
AE
Bultink
I E M
IE
Ruffatti
A
A
Rozman
B
B
Kveder
T
T
de Moerloose
P
P
Boehlen
F
F
Rand
J
J
Ulcova-Gallova
Z
Z
Mertens
K
K
de Groot
P G
PG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017152:Antibodies, Antiphospholipid; D016736:Antiphospholipid Syndrome / Q000175:diagnosis / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology; D013927:Thrombosis / Q000175:diagnosis / Q000276:immunology*; D055815:Young Adult; D053482:beta 2-Glycoprotein I / Q000276:immunology*
D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D053482:beta 2-Glycoprotein I