Clinical significance of β2-glycoprotein I-dependent anticardiolipin antibodies in the reproductive autoimmune failure syndrome: Correlation with conventional antiphospholipid antibody detection systems

OBJECTIVE: Our purpose was to determine whether β2-glycoprotein I-dependent anticardiolipin antibodies may represent a superior marker of reproducible risk than do conventional antiphospholipid antibodies. STUDY DESIGN: The incidence of β2-glycoprotein I-dependent and β2-glycoprotein I-independent anticardiolipin antibodies and of six conventional antiphospholipid antibodies was statistically compared between study groups with and without autoantibody-associated features of reproductive failure. Sera from 356 women were randomly selected from the frozen sera bank at the Center for Human Reproduction, Chicago. They included sera from 259 patients with autoantibody-associated features of infertile controls. Autoantibody levels by a modified enzyme-linked immunosorbent assay for β2-glycoprotein I-dependent and β2-glycoprotein I-independent anticardiolipin antibodies and a standard enzyme-linked immunosorbent assay for anticardiolipin antibody and five other antiphospholipid antibodies were then compared. RESULTS: Patients demonsrated a significantly higher incidence of β2-glycoprotein I-dependent anticardiolipin antibodies (5.4%) than did controls (0%). In a modified enzyme-linked immunosorbent assay (p = 0.01). No such difference was, however, noted for β2-glycoprotein I-independent anticardiolipin antibodies or any one of six antiphospholipid antibodies. Two or more among six antiphospholipid antibodies, especially if involving anticardiolipin antibodies, antiphosphatidylserine and antiphosphatidylinositol, as assayed by standard enzyme-linked immunosorbent assay, were significantly more often (p = 0.02) positive in the patients (5.0%) than in the controls (0%). Moreover, positivity in two of those three antiphospholipid antibodies correlated in 59% of cases to positivity in the β2-glycoprotein I-dependent anticardiolipin antibody. CONCLUSIONS: As a single test β2-glycoprotein I-dependent anticardiolipin antibody appears to be superior to cofactor-independent anticardiolipin antibody or any other single conventional antiphospholipid antibody for the detection of autoantibody associated conditions of reproductive failure. A broadly based panel of conventional antiphospholipid antibodies especially if inclusive of anticardiolipid antibody, ant phosphatidylserine, and antiphosphatidylinositol, may, however, achieve siimlar results.