title: Clinical implications of the detection of antibodies directed against domain 1 of β2-glycoprotein 1 in thrombotic antiphospholipid syndrome.
abstract: BACKGROUND
  Antibodies directed against domain 1 of β2 glycoprotein 1 (aβ2GP1-Dm1) have been involved in the immunopathogenesis of antiphospholipid syndrome (APS). However, the clinical relevance of aβ2GP1-Dm1 in thrombotic APS has not yet been fully explored.
  
  
  OBJECTIVE
  To determine the frequency of aβ2GP1-Dm1 in a cohort of patients with thrombotic APS, and to evaluate whether testing for aβ2GP1-Dm1 could have a clinical impact upon the risk assessment of the disease.
  
  
  METHODS
  Patients were tested for aβ2GP1-Dm1 antibodies by chemiluminescence (BioFlash/AcuStar®, ES). The presence of aβ2GP1-Dm1 was evaluated in different clinical presentations of the disease.
  
  
  RESULTS
  Eight-four patients with a history of venous or arterial thrombosis were included. Forty-five (54%) patients had aβ2GP1 antibodies and 40% of them were positive for aβ2GP1-Dm1. Levels of aβ2GP1-Dm1 were higher in patients with systemic autoimmune disease (AUC=0.665; 95% CI=0.544-0.786; P=0.01), positive antinuclear antibody (AUC=0.654; 95% CI=0.535-0.772; P=0.01), triple antiphospholipid antibody (aPL) positivity (AUC=0.680; 95% CI=0.534-0.825; P=0.02) and positive lupus anticoagulant (AUC=0.639; 95% CI=0.502-0.776; P=0.07). In this cohort, aβ2GP1-Dm1 antibodies were not associated with the site of the first thrombosis (OR=0,62, 95% CI=0.20-1.94, P=0.42), thrombosis recurrence (OR=1.0, 95% CI=0.37-2.71, P=1.0) or pregnancy morbidity (OR=1.5, 95% CI=0.33-7.34, P=0.58). In multivariate analysis, positivity for aβ2GP1-Dm1 antibodies was associated with the diagnosis of systemic autoimmune disease (OR=4.01, 95% CI=1.14-14.2; P=0.03) and triple aPL positivity (OR=3.59, 95% CI=0.87-14.85; P=0.07).
  
  
  CONCLUSIONS
  In the present cohort of thrombotic-APS patients, aβ2GP1-Dm1 antibodies were related to the diagnosis of systemic autoimmunity and complex serological profile of the disease, as triple aPL positivity and positive antinuclear antibody. Thus, our results suggest that testing for aβ2GP1-Dm1 antibodies may be useful for improving APS risk assessment.
authors: Laboratory of Haemostasis, Hematology and Hemotherapy Center, University of Campinas, Rua Carlos Chagas, 480, Cidade Universitária "Zeferino Vaz", CEP: 13083-970 Campinas, SP, Brazil. Electronic address: silmara@unicamp.br.
authors: Silmara
authors: S
authors: Montalvão
authors: Laboratory of Haemostasis, Hematology and Hemotherapy Center, University of Campinas, Rua Carlos Chagas, 480, Cidade Universitária "Zeferino Vaz", CEP: 13083-970 Campinas, SP, Brazil. Electronic address: pri_kelidio@hotmail.com.
authors: Priscila Soares
authors: PS
authors: Elídio
authors: Laboratory of Haemostasis, Hematology and Hemotherapy Center, University of Campinas, Rua Carlos Chagas, 480, Cidade Universitária "Zeferino Vaz", CEP: 13083-970 Campinas, SP, Brazil. Electronic address: sabrina_saraiva@yahoo.com.br.
authors: Sabrina
authors: S
authors: da Silva Saraiva
authors: Laboratory of Haemostasis, Hematology and Hemotherapy Center, University of Campinas, Rua Carlos Chagas, 480, Cidade Universitária "Zeferino Vaz", CEP: 13083-970 Campinas, SP, Brazil. Electronic address: brunamazetto_1@hotmail.com.
authors: Bruna
authors: B
authors: de Moraes Mazetto
authors: Laboratory of Haemostasis, Hematology and Hemotherapy Center, University of Campinas, Rua Carlos Chagas, 480, Cidade Universitária "Zeferino Vaz", CEP: 13083-970 Campinas, SP, Brazil. Electronic address: marinasp@unicamp.br.
authors: Marina Pereira
authors: MP
authors: Colella
authors: Laboratory of Haemostasis, Hematology and Hemotherapy Center, University of Campinas, Rua Carlos Chagas, 480, Cidade Universitária "Zeferino Vaz", CEP: 13083-970 Campinas, SP, Brazil; Discipline of Hematology and Hemotherapy, Department of Clinical Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", CEP: 13083-887 Campinas, SP, Brazil. Electronic address: erich@unicamp.br.
authors: Erich Vinícius
authors: EV
authors: de Paula
authors: Rheumatology Unit, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", CEP: 13083-887 Campinas, SP, Brazil. Electronic address: appenzellersimone@gmail.com.
authors: Simone
authors: S
authors: Appenzeller
authors: Laboratory of Haemostasis, Hematology and Hemotherapy Center, University of Campinas, Rua Carlos Chagas, 480, Cidade Universitária "Zeferino Vaz", CEP: 13083-970 Campinas, SP, Brazil; Discipline of Hematology and Hemotherapy, Department of Clinical Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", CEP: 13083-887 Campinas, SP, Brazil. Electronic address: joyce@unicamp.br.
authors: Joyce
authors: J
authors: Annichino-Bizzacchi
authors: Laboratory of Haemostasis, Hematology and Hemotherapy Center, University of Campinas, Rua Carlos Chagas, 480, Cidade Universitária "Zeferino Vaz", CEP: 13083-970 Campinas, SP, Brazil; Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, Brazil Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", CEP: 13083-887 Campinas, SP, Brazil. Electronic address: ferorsi@unicamp.br.
authors: Fernanda Andrade
authors: FA
authors: Orsi
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D017152:Antibodies, Antiphospholipid / Q000097:blood / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications* / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013927:Thrombosis / Q000097:blood / Q000150:complications* / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D000906:Antibodies; D017152:Antibodies, Antiphospholipid; D016682:Lupus Coagulation Inhibitor; D053482:beta 2-Glycoprotein I
keywords: Antibodies; Antiphospholipid; Domain 1; Prognosis