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Dual antibody reactivity to ß2-glycoprotein I and protein S: increased association with thrombotic events in the antiphospholipid syndrome

Division of Rheumatology, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, USA

H W Zhang

Department of Rheumatology, Hospital for Joint Diseases, New York, USA

R C Shriky

Department of Rheumatology, Hospital for Joint Diseases, New York, USA; Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma

J T Merrill

Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, OK 73104, USA,JTMmail{at}aol.com

The antiphospholipid syndrome (APS) is a thrombotic disorder leading to spontaneous abortions, venous thromboses, myocardial infarctions and strokes. Although the syndrome is associated with characteristic autoantibodies, these tests have poor predictive value for thrombosis.

The aim of the study was to determine whether the combined presence of two types of antiphospholipidantibodies can be associated with a high-risk subset of thrombosis-prone patients.

One hundred and thirty-four sera from a lupus clinic were tested for antibodies to ß₂-glycoprotein I (ß₂GPI), protein S and prothrombin. In a group of 29 patients for whom plasma was available, free (functional) protein S levels were also measured.

Autoantibodies to ß₂GPI and protein S are associated with each other. Dual reactivity to ß₂GPI and protein S correlates with increased history of thrombotic events (69% of doubly reactive patients) when compared to either type of autoantibodyalone (37% of patients with only anti-ß₂GPI and 38% with only anti-protein S, P=0.04 and P=0.01, respectively) or neither reactivity (37%). Among 29 patients tested for free (functional, anticoagulant)protein S levels, the lowest levels were found in patients with antibodies to ß₂GPI and/or protein S, and all four patients with a history of thrombosis had below-normal free protein S levels. These associations were not found with antiprothrombin antibodies.

In conclusion dual autoantibodiesto ß₂GPI and protein S are associated with increased history of thrombosis in the antiphospholipid syndrome.

Key Words: dual reactivity • antiphospholipid syndrome

Lupus, Vol. 11, No. 4, 215-220 (2002)
DOI: 10.1191/0961203302lu178oa


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