title: The antiphospholipid/cofactor syndromes: a primary variant with antibodies to beta 2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays.
abstract: BACKGROUND
  Most systemic lupus erythematosus (SLE) patients with two or more clinical manifestations of the antiphospholipid syndrome (APS) and negative antiphospholipid antibodies (aPL) have antibodies to beta 2-glycoprotein-I (a beta 2 GP-I). Herein we describe a similar set of circumstances, but in patients without evidence of SLE.
  
  
  METHODS
  We studied 6 patients with recurrent venous and/or arterial thromboses without aPL as detected by routine assays nor clinical or serological evidence of other autoimmune disease. Immunoglobin (Ig) G and IgM antibodies to bovine and human phospholipid-free beta 2 GP-I were studied by Western blot test and by enzyme-linked immunosorbent assay (ELISA) utilizing radiated and nonirradiated plates. We also tested antibodies to cardiolipin, phosphatidylserine, and phosphatidylethanolamine by ELISA. As controls, 54 normal sera were studied.
  
  
  RESULTS
  All 6 patients had recurrent arterial and/or venous thromboses. Three also had thrombocytopenia, 1 had livedo reticularis, and 2 had valvular heart disease. None of the patients had aPL, but all had serum IgG reactivity against human and bovine beta 2 GP-I (P < 0.001 versus controls for both). Titers of anti-bovine beta 2 GP-I were higher when studied in irradiated plates but were also higher than normal in nonirradiated plates (P < 0.001). These antibodies did not recognize human or bovine beta 2 GP-I bound to cardiolipin in solid phase. We confirmed by Western blot that these autoantibodies recognize human beta 2 GP-I. We found no IgM a beta 2 GP-I.
  
  
  CONCLUSIONS
  We describe a primary condition akin to the antiphospholipid syndrome with negative aPL, but with serum IgG antibodies to human and bovine beta 2 GP-I. These antibodies recognize beta 2 GP-I epitopes that are not accessible when beta 2 GP-I is bound to cardiolipin.
authors.affiliation: Department of Immunology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, DF, Mexico.
authors.forename: A R
authors.initials: AR
authors.lastname: Cabral
authors.forename: M C
authors.initials: MC
authors.lastname: Amigo
authors.forename: J
authors.initials: J
authors.lastname: Cabiedes
authors.forename: D
authors.initials: D
authors.lastname: Alarcon-Segovia
mesh_terms: D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D015153:Blotting, Western; D002308:Cardiolipins / Q000276:immunology; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005165:Factor V; D005260:Female; D005838:Genotype; D006023:Glycoproteins / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010714:Phosphatidylethanolamines / Q000276:immunology; D010718:Phosphatidylserines / Q000276:immunology; D011486:Protein C; D013577:Syndrome; D013927:Thrombosis / Q000276:immunology*; D053482:beta 2-Glycoprotein I
chemical_list: D001323:Autoantibodies; D002308:Cardiolipins; D000939:Epitopes; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D011486:Protein C; D053482:beta 2-Glycoprotein I; D005165:Factor V