Double positivity of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies enhances both thrombosis and positivity of anti-ADAMTS13 antibody

Although a few antiphospholipid syndrome (APS) occurs with acquired thrombotic thrombocytopenic purpura (TTP), the relationship between antiphospholipid antibodies (aPL) and anti-ADAMTS13 (anti-a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) antibody remains uncertain. We investigated the relationship between high-risk thrombotic aPL and anti-ADAMTS13 antibody. Two hundred and thirty-seven patients with positive lupus anticoagulant and/or anticardiolipin antibody were included. Anti-beta(2)GPI (anti-beta(2)-glycoprotein I), anti-beta(2)GPIdI (anti-beta 2-glycoprotein I domain I), anti-PS/PT (anti-phosphatidylserine and prothrombin), ADAMTS13 activity, and anti-ADAMTS13 antibody were measured. Double positivity of anti-beta(2)GPI and anti-PS/PT increased thrombotic risk more than three-fold and showed increased positivity of anti-ADAMTS13 antibody in comparison with the double negative group. Double positivity of anti-beta(2)GPIdI and anti-PS/PT presented both effects even more. In the linear regression analysis, double positivity of anti-beta(2)GPI and anti-PS/PT independently affected the anti-ADAMTS13 antibody level (beta = 1.982, P = 0.042). Our results revealed that double positivity of anti-beta(2)GPI or anti-beta(2)GPIdI and anti-PS/PT increased not only thrombotic risk but also the positivity of anti-ADAMTS13 antibody, especially indicating anti-beta(2)GPIdI showed a higher synergistic effect with anti-PS/PT. We suggest a possible association of anti-ADAMTS13 antibody with a high thrombotic risk of APS. Double positivity of anti-beta 2GPI (anti-beta 2-glycoprotein I) and anti-PS/PT (anti-phosphatidylserine and prothrombin) antibodies enhanced not only thrombotic risk but also positivity of anti-ADAMTS13 (anti-a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) antibody. Furthermore, double positivity of anti-beta 2GPIdI (anti-beta 2-glycoprotein I domain I) combined with anti-PS/PT even more elevated both thrombosis and positivity of anti-ADAMTS13 antibody. Double positivity of beta 2GPI and anti-PS/PT was found as an independently significant contributing factor to anti-ADAMTS13 antibody level. We suggest the association between anti-ADAMTS13 antibody and the pathophysiology of antiphospholipid syndrome, which should be further evaluated.