title: Circulating Immune Complexes of IgA Bound to Beta 2 Glycoprotein are Strongly Associated with the Occurrence of Acute Thrombotic Events.
abstract: OBJECTIVE
  Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis and/or gestational morbidity in patients with antiphospholipid autoantibodies (aPL). Over recent years, IgA anti-beta2-glycoprotein I (B2GPI) antibodies (IgA aB2GPI) have reached similar clinical relevance as IgG or IgM isotypes. We recently described the presence of immune complexes of IgA bounded to B2GPI (B2A-CIC) in the blood of patients with antecedents of APS symptomalology. However, B2A-CIC's clinical associations with thrombotic events (TEV) have not been described yet.
  
  
  METHODS
  A total of 145 individuals who were isolate positive for IgA aB2GPI were studied: 50 controls without any APS antecedent, 22 patients with recent TEV (Group-1), and 73 patients with antecedents of old TEV (Group-2).
  
  
  RESULTS
  Mean B2A-CIC levels and prevalence in Group-1 were 29.6±4.1 AU and 81.8%, respectively, and were significantly higher than those of Group-2 and controls (p＜0.001). In a multivariable analysis, positivity of B2A-CIC was an independent variable for acute thrombosis with a 22.7 odd ratio (confidence interval 5.1-101.6, 95%, p＜0.001). Levels of B2A-CIC dropped significantly two months after the TEV. B2A-CIC positive patients had lower platelet levels than B2A-CIC-negative patients (p＜0.001) and more prevalence of thrombocytopenia (p＜0.019). Group-1 had no significant differences in C3 and C4 levels compared with other groups.
  
  
  CONCLUSIONS
  B2A-CIC is strongly associated with acute TEV. Patients who did not develop thrombosis and were B2A-CIC positive had lower platelet levels, which suggest a hypercoagulable state. This mechanism is unrelated to complement-fixing aPL. B2A-CIC could potentially select IgA aB2GPI-positive patients at risk of developing a thrombotic event.
authors.affiliation: Department of Immunology, Instituto de Investigación, Hospital Universitario 12 de Octubre.
authors.forename: José A
authors.initials: JA
authors.lastname: Martínez-Flores
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
authors.forename: Dolores
authors.initials: D
authors.lastname: Pérez
authors.forename: Gómez de la
authors.initials: G
authors.lastname: Cámara A
authors.forename: David
authors.initials: D
authors.lastname: Lora
authors.forename: Luis
authors.initials: L
authors.lastname: Morillas
authors.forename: Rosa
authors.initials: R
authors.lastname: Ayala
authors.forename: Estela
authors.initials: E
authors.lastname: Paz-Artal
authors.forename: José M
authors.initials: JM
authors.lastname: Morales
authors.forename: Antonio
authors.initials: A
authors.lastname: Serrano
mesh_terms: D000368:Aged; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D013927:Thrombosis / Q000503:physiopathology*; D053482:beta 2-Glycoprotein I / Q000097:blood / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D015415:Biomarkers; D007070:Immunoglobulin A; D053482:beta 2-Glycoprotein I