title: Pathogenic antibodies in women with obstetric features of antiphospholipid syndrome who have negative test results for lupus anticoagulant and anticardiolipin antibodies.
abstract: OBJECTIVE
  Our goal was to determine whether women with clinical features of antiphospholipid syndrome but negative test results for lupus anticoagulant and anticardiolipin antibodies have pathogenic antibodies not identified by currently used methods.
  
  
  METHODS
  Sera were obtained from women with clinical features associated with antiphospholipid antibodies who had negative test results for lupus anticoagulant and anticardiolipin antibodies (antiphospholipid syndrome-like). We studied (1) the effect of passive immunization with their purified immunoglobulin G fraction on murine pregnancy (n = 35) and (2) the presence of antiphospholipid antibodies other than lupus anticoagulant or anticardiolipin antibodies (n = 39). Sera were also retested for anticardiolipin antibodies and lupus anticoagulant.
  
  
  RESULTS
  Fetal loss occurred in 235 of 1088 (22%) pups in 137 mice immunized with immunoglobulin G fraction from antiphospholipid syndrome-like women compared with 23 of 402 (6%) pups in 53 control mice. Immunoglobulin G from 11 study patients resulted in the loss of at least one third of the exposed pups. Five women had positive levels of antiphosphatidylserine antibodies (>99th percentile). All levels were low positive, and three women also had low-positive levels of anticardiolipin antibodies on repeat testing. Five of the 11 (45%) women whose immunoglobulin G fractions caused at least 33% fetal loss also had positive test results for antiphospholipid antibodies.
  
  
  CONCLUSIONS
  A subset of women with clinical disorders suspicious for antiphospholipid syndrome but who had negative test results for lupus anticoagulant and anticardiolipin antibodies by current methods have serum immunoglobulin G that is pathogenic to murine pregnancy. Testing for pathogenic immunoglobulin G may provide additional means to identify women with an as yet uncharacterized immune condition. The clinical relevance of low levels of antiphospholipid antibodies in these women remains unproved.
authors.affiliation: Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City 84132, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Silver
authors.forename: S S
authors.initials: SS
authors.lastname: Pierangeli
authors.forename: S S
authors.initials: SS
authors.lastname: Edwin
authors.forename: F
authors.initials: F
authors.lastname: Umar
authors.forename: E N
authors.initials: EN
authors.lastname: Harris
authors.forename: J R
authors.initials: JR
authors.lastname: Scott
authors.forename: D W
authors.initials: DW
authors.lastname: Branch
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology*; D005260:Female; D005313:Fetal Death / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D016682:Lupus Coagulation Inhibitor / Q000097:blood; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*
chemical_list: D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D016682:Lupus Coagulation Inhibitor