title: Clinical significance of beta 2-glycoprotein I-dependent anticardiolipin antibodies in the reproductive autoimmune failure syndrome: correlation with conventional antiphospholipid antibody detection systems.
abstract: OBJECTIVE
  Our purpose was to determine whether beta 2-glycoprotein I-dependent anticardiolipin antibodies may represent a superior marker of reproductive risk than do conventional antiphospholipid antibodies.
  
  
  METHODS
  The incidence of beta 2-glycoprotein I-dependent and beta 2-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 reproductive failure such as unexplained infertility, endometriosis, and repeated pregnancy loss and 97 infertile controls. Autoantibody levels by a modified enzyme-linked immunosorbent assay for beta 2-glycoprotein I-dependent and beta 2-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 demonstrated a significantly higher incidence of beta 2-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 beta 2-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 beta 2-glycoprotein I-dependent anticardiolipin antibody.
  
  
  CONCLUSIONS
  As a single test beta 2-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, antiphosphatidylserine, and antiphosphatidylinositol, may, however, achieve similar results.
authors.affiliation: Center for Human Reproduction, Chicago, IL 60610.
authors.forename: K
authors.initials: K
authors.lastname: Aoki
authors.forename: A B
authors.initials: AB
authors.lastname: Dudkiewicz
authors.forename: E
authors.initials: E
authors.lastname: Matsuura
authors.forename: M
authors.initials: M
authors.lastname: Novotny
authors.forename: G
authors.initials: G
authors.lastname: Kaberlein
authors.forename: N
authors.initials: N
authors.lastname: Gleicher
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology; D017153:Antibodies, Anticardiolipin / Q000097:blood*; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D001053:Apolipoproteins / Q000097:blood; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007247:Infertility, Female / Q000276:immunology; D011247:Pregnancy; D012098:Reproduction / Q000276:immunology*; D012307:Risk Factors; D013577:Syndrome; D053482:beta 2-Glycoprotein I
chemical_list: D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D001053:Apolipoproteins; D015415:Biomarkers; D006023:Glycoproteins; D007074:Immunoglobulin G; D053482:beta 2-Glycoprotein I