title: Autoantibodies to Factor XII and Kininogen-Dependent Antiphosphatidylethanolamine Antibodies in Patients with Recurrent Pregnancy Loss Augment Platelet Aggregation.
abstract: OBJECTIVE
  Numerous studies have suggested that factor XII (FXII) deficiency, autoantibodies to FXII (anti-FXII), and antiphosphatidylethanolamine antibodies (aPE) are associated with recurrent pregnancy loss (RPL). aPE in RPL patients recognize the LDC27 peptide of kininogen domain 3. Anti-FXII in RPL patients recognizes the heavy chain of FXII, especially the amino-terminal sequences IPP30 peptide. Previous studies suggested that LDC27 and IPP30 are the responsible sites competing for the same binding site on platelets and inhibiting augmentation of thrombin-induced platelet aggregation. Our aim was to study the influence of antibodies to LDC27 and IPP30 on platelet aggregation.
  
  
  METHODS
  In fifteen healthy volunteers, platelet aggregation induced by γ-thrombin in the presence or absence of antibodies to LDC27 and IPP30 was measured. Sixteen RPL patients who were positive for anti-FXII were measured for spontaneous small platelet aggregate (SSPA) formation.
  
  
  CONCLUSIONS
  Antibodies to LDC27 and IPP30 markedly increased aggregation of normal platelets stimulated by γ-thrombin. Augmentation of SSPA formation was more frequent in the patients with RPL who were positive for anti-FXII than in the control group (P = 0.003). This study strongly supports the hypothesis that aPE and anti-FXII may cause RPL due to disruption of the normal antithrombotic effects of kininogens and FXII.
authors.affiliation: Laboratory for Recurrent Pregnancy Loss, Sugi Women's Clinic, Yokohama, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Laboratory for Recurrent Pregnancy Loss, Sugi Women's Clinic, Yokohama, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Sugi
authors.affiliation: Laboratory for Recurrent Pregnancy Loss, Sugi Women's Clinic, Yokohama, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Sakai
mesh_terms: D000026:Abortion, Habitual / Q000097:blood / Q000276:immunology*; D000328:Adult; D001323:Autoantibodies / Q000494:pharmacology*; D005174:Factor XII / Q000276:immunology*; D005260:Female; D006801:Humans; D007704:Kininogens / Q000276:immunology*; D010714:Phosphatidylethanolamines / Q000276:immunology*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000276:immunology; D011247:Pregnancy
chemical_list: D001323:Autoantibodies; D007704:Kininogens; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D005174:Factor XII
keywords: Antiphosphatidylethanolamine antibodies; factor XII; kininogen; platelet aggregation; recurrent pregnancy loss