title: Activated protein C resistance and lupus anticoagulant activity induced by plasma and purified monospecific human IgG anti-beta2-glycoprotein-I antibodies.
abstract: BACKGROUND
  We investigated the activated protein C resistance (APCR) phenotype and the lupus anticoagulant (LA), activity induced by anti-beta2-glycoprotein-I (anti-beta2GP-I) antibodies.
  
  
  METHODS
  We studied plasma and sera samples from 29 patients with persistently positive anti-beta2GP-I: 22 with thrombosis (12 with primary APS, 10 with APS secondary to SLE) and seven without thrombosis (all with SLE); 25 healthy subjects were studied as controls. We detected anticardiolipin antibodies (ACA); IgG (and its subclasses) and IgM anti-beta2GP-I, on irradiated and non-irradiated plates by ELISA. APCR was assessed by the activated partial thromboplastin time (APTT)-based assay and by the modified test. The FV Leiden mutation was studied by PCR. LA determination included screening and confirmatory dRVVT. Serum anti-2 GP-I were affinity purified on sepharose columns and their isotype, subclass, and reactivity against various antigens were studied by ELISA.
  
  
  RESULTS
  We found that titers of IgG anti-beta2GP-I on irradiated plates were higher than on non-irradiated plates (p = 0.002), IgG2 was the predominant subclass. Fifteen patients (13 with thrombosis) had LA and 15 (also 13 with thrombosis) induced the APCR phenotype. Eleven (all with thrombosis) had both. Two patients were heterozygous for the Leiden mutation. Two purified antibodies, monospecific for beta2GP-I, induced an in vitro APCR phenotype and LA activity.
  
  
  CONCLUSIONS
  Our results seem to indicate that the inhibition of the APC anticoagulant function by IgG2 anti-beta2GP-I with LA activity may be one of the responsible mechanisms of thrombophilia in patients with APS.
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Viveros
authors.forename: Javier
authors.initials: J
authors.lastname: Cabiedes
authors.forename: Elba
authors.initials: E
authors.lastname: Reyes
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Cabral
mesh_terms: D020016:Activated Protein C Resistance / Q000209:etiology / Q000276:immunology*; D000328:Adult; D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology* / Q000302:isolation & purification; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005165:Factor V / Q000032:analysis / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000494:pharmacology; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010641:Phenotype; D010949:Plasma; D010969:Plastics / Q000528:radiation effects; D011517:Prothrombin Time; D019851:Thrombophilia / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D053482:beta 2-Glycoprotein I
chemical_list: D017153:Antibodies, Anticardiolipin; D001323:Autoantibodies; D001324:Autoantigens; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016682:Lupus Coagulation Inhibitor; D010969:Plastics; D053482:beta 2-Glycoprotein I; C095381:factor V Leiden; D005165:Factor V