Silmara Montalvão1, Priscila Soares Elídio2, Sabrina da Silva Saraiva3, Bruna de Moraes Mazetto4, Marina Pereira Colella5, Erich Vinícius de Paula6, Simone Appenzeller7, Joyce Annichino-Bizzacchi8, Fernanda Andrade Orsi9. 1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. 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. 9. 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.
Abstract
INTRODUCTION: 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. OBJECTIVES: 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.
INTRODUCTION: 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. OBJECTIVES: 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-APSpatients, 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: Camila de O Vaz; Bruna M Mazetto; Pedro Eduardo Nascimento Silva Vasconcelos; Larissa Brito Bastos; Maria Aparecida Cursino; Júlia Coelho França Quintanilha; Gabriela Lisiane Tripiquia Vechiatto Mesquita; Ana Paula Rosa Dos Santos; Bruna Cardoso Jacintho; José Diogo Oliveira; Joyce Annichino-Bizzacchi; Fernanda Andrade Orsi Journal: J Thromb Thrombolysis Date: 2022-04-13 Impact factor: 5.221
Authors: Camila O Vaz; Bruna M Mazetto; Pedro Eduardo N S Vasconcelos; Larissa B Bastos; Maria Aparecida Cursino; Júlia Coelho França Quintanilha; Gabriela Lisiane Tripiquia Vechiatto Mesquita; Ana Paula R Santos; Bruna Cardoso Jacintho; José Diogo Oliveira; Joyce Annichino-Bizzachi; Fernanda A Orsi Journal: J Thromb Thrombolysis Date: 2021-07-05 Impact factor: 2.300