Clinical implications of the detection of antibodies directed against domain 1 of β2-glycoprotein 1 in thrombotic antiphospholipid syndrome

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 f...

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Veröffentlicht in:Thrombosis research 2016-12, Vol.148, p.32-37
Hauptverfasser: Montalvão, Silmara, Soares, Priscila Elídio, da Silva Saraiva, Sabrina, de Moraes Mazetto, Bruna, Colella, Marina Pereira, de Paula, Erich Vinícius, Appenzeller, Simone, Annichinno-Bizzachi, Joyce, Orsi, Fernanda Andrade, MD, PhD
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container_issue
container_start_page 32
container_title Thrombosis research
container_volume 148
creator Montalvão, Silmara
Soares, Priscila Elídio
da Silva Saraiva, Sabrina
de Moraes Mazetto, Bruna
Colella, Marina Pereira
de Paula, Erich Vinícius
Appenzeller, Simone
Annichinno-Bizzachi, Joyce
Orsi, Fernanda Andrade, MD, PhD
description 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.
doi_str_mv 10.1016/j.thromres.2016.10.001
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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.</description><identifier>ISSN: 0049-3848</identifier><identifier>EISSN: 1879-2472</identifier><identifier>DOI: 10.1016/j.thromres.2016.10.001</identifier><identifier>PMID: 27770664</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Adult ; Antibodies ; Antibodies - blood ; Antibodies - immunology ; Antibodies, Antiphospholipid - blood ; Antibodies, Antiphospholipid - immunology ; Antiphospholipid ; Antiphospholipid Syndrome - blood ; Antiphospholipid Syndrome - complications ; Antiphospholipid Syndrome - immunology ; beta 2-Glycoprotein I - immunology ; Cohort Studies ; Domain 1 ; Female ; Hematology, Oncology and Palliative Medicine ; Humans ; Lupus Coagulation Inhibitor - blood ; Lupus Coagulation Inhibitor - immunology ; Male ; Middle Aged ; Prognosis ; Thrombosis - blood ; Thrombosis - complications ; Thrombosis - immunology</subject><ispartof>Thrombosis research, 2016-12, Vol.148, p.32-37</ispartof><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c338t-a20498535eff57647a25cd6f49d1f86a1ff486e8b2d92da4b9bebb150684c7aa3</citedby><cites>FETCH-LOGICAL-c338t-a20498535eff57647a25cd6f49d1f86a1ff486e8b2d92da4b9bebb150684c7aa3</cites><orcidid>0000-0002-5942-1083</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0049384816305758$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27770664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Montalvão, Silmara</creatorcontrib><creatorcontrib>Soares, Priscila Elídio</creatorcontrib><creatorcontrib>da Silva Saraiva, Sabrina</creatorcontrib><creatorcontrib>de Moraes Mazetto, Bruna</creatorcontrib><creatorcontrib>Colella, Marina Pereira</creatorcontrib><creatorcontrib>de Paula, Erich Vinícius</creatorcontrib><creatorcontrib>Appenzeller, Simone</creatorcontrib><creatorcontrib>Annichinno-Bizzachi, Joyce</creatorcontrib><creatorcontrib>Orsi, Fernanda Andrade, MD, PhD</creatorcontrib><title>Clinical implications of the detection of antibodies directed against domain 1 of β2-glycoprotein 1 in thrombotic antiphospholipid syndrome</title><title>Thrombosis research</title><addtitle>Thromb Res</addtitle><description>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.</description><subject>Adult</subject><subject>Antibodies</subject><subject>Antibodies - blood</subject><subject>Antibodies - immunology</subject><subject>Antibodies, Antiphospholipid - blood</subject><subject>Antibodies, Antiphospholipid - immunology</subject><subject>Antiphospholipid</subject><subject>Antiphospholipid Syndrome - blood</subject><subject>Antiphospholipid Syndrome - complications</subject><subject>Antiphospholipid Syndrome - immunology</subject><subject>beta 2-Glycoprotein I - immunology</subject><subject>Cohort Studies</subject><subject>Domain 1</subject><subject>Female</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Lupus Coagulation Inhibitor - blood</subject><subject>Lupus Coagulation Inhibitor - immunology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prognosis</subject><subject>Thrombosis - blood</subject><subject>Thrombosis - complications</subject><subject>Thrombosis - immunology</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUstu1DAUtRCITgu_UGXJJoPt-JUNAo0oVKrEAlhbjn3T8ZDEwfZUmn_ga_ohfBPOzJQFGxa2r4_Pffjci9A1wWuCiXi7W-dtDGOEtKblXsA1xuQZWhEl25oySZ-jFcasrRvF1AW6TGlXCJK0_CW6oFJKLARboV-bwU_emqHy4zwUI_swpSr0Vd5C5SCDXZAFMFP2XXAeUuV8LDi4ytwbP6VcuTAWoyIL7_cjre-Hgw1zDBmOaNmO5XYhe3sMNG9DKmvws3dVOkyuvMIr9KI3Q4LX5_MKfb_5-G3zub778ul28-Gutk2jcm1o-ZfiDYe-51IwaSi3TvSsdaRXwpC-Z0qA6qhrqTOsazvoOsKxUMxKY5or9OYUt1T4cw8p69EnC8NgJgj7pIlqOKeEYlmo4kS1MaQUoddz9KOJB02wXjqhd_qpE3rpxIIXoYvj9TnHvhvB_XV7kr4Q3p8IUH764CHqZD1MFk7iahf8_3O8-yeEPXfzBxwg7cI-TkVHTXSiGuuvyzws40BEg7nkqvkDQqK2sw</recordid><startdate>20161201</startdate><enddate>20161201</enddate><creator>Montalvão, Silmara</creator><creator>Soares, Priscila Elídio</creator><creator>da Silva Saraiva, Sabrina</creator><creator>de Moraes Mazetto, Bruna</creator><creator>Colella, Marina Pereira</creator><creator>de Paula, Erich Vinícius</creator><creator>Appenzeller, Simone</creator><creator>Annichinno-Bizzachi, Joyce</creator><creator>Orsi, Fernanda Andrade, MD, PhD</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5942-1083</orcidid></search><sort><creationdate>20161201</creationdate><title>Clinical implications of the detection of antibodies directed against domain 1 of β2-glycoprotein 1 in thrombotic antiphospholipid syndrome</title><author>Montalvão, Silmara ; Soares, Priscila Elídio ; da Silva Saraiva, Sabrina ; de Moraes Mazetto, Bruna ; Colella, Marina Pereira ; de Paula, Erich Vinícius ; Appenzeller, Simone ; Annichinno-Bizzachi, Joyce ; Orsi, Fernanda Andrade, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c338t-a20498535eff57647a25cd6f49d1f86a1ff486e8b2d92da4b9bebb150684c7aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Antibodies</topic><topic>Antibodies - blood</topic><topic>Antibodies - immunology</topic><topic>Antibodies, Antiphospholipid - blood</topic><topic>Antibodies, Antiphospholipid - immunology</topic><topic>Antiphospholipid</topic><topic>Antiphospholipid Syndrome - blood</topic><topic>Antiphospholipid Syndrome - complications</topic><topic>Antiphospholipid Syndrome - immunology</topic><topic>beta 2-Glycoprotein I - immunology</topic><topic>Cohort Studies</topic><topic>Domain 1</topic><topic>Female</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Lupus Coagulation Inhibitor - blood</topic><topic>Lupus Coagulation Inhibitor - immunology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prognosis</topic><topic>Thrombosis - blood</topic><topic>Thrombosis - complications</topic><topic>Thrombosis - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Montalvão, Silmara</creatorcontrib><creatorcontrib>Soares, Priscila Elídio</creatorcontrib><creatorcontrib>da Silva Saraiva, Sabrina</creatorcontrib><creatorcontrib>de Moraes Mazetto, Bruna</creatorcontrib><creatorcontrib>Colella, Marina Pereira</creatorcontrib><creatorcontrib>de Paula, Erich Vinícius</creatorcontrib><creatorcontrib>Appenzeller, Simone</creatorcontrib><creatorcontrib>Annichinno-Bizzachi, Joyce</creatorcontrib><creatorcontrib>Orsi, Fernanda Andrade, MD, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Thrombosis research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Montalvão, Silmara</au><au>Soares, Priscila Elídio</au><au>da Silva Saraiva, Sabrina</au><au>de Moraes Mazetto, Bruna</au><au>Colella, Marina Pereira</au><au>de Paula, Erich Vinícius</au><au>Appenzeller, Simone</au><au>Annichinno-Bizzachi, Joyce</au><au>Orsi, Fernanda Andrade, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical implications of the detection of antibodies directed against domain 1 of β2-glycoprotein 1 in thrombotic antiphospholipid syndrome</atitle><jtitle>Thrombosis research</jtitle><addtitle>Thromb Res</addtitle><date>2016-12-01</date><risdate>2016</risdate><volume>148</volume><spage>32</spage><epage>37</epage><pages>32-37</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><abstract>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.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>27770664</pmid><doi>10.1016/j.thromres.2016.10.001</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-5942-1083</orcidid></addata></record>
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subjects Adult
Antibodies
Antibodies - blood
Antibodies - immunology
Antibodies, Antiphospholipid - blood
Antibodies, Antiphospholipid - immunology
Antiphospholipid
Antiphospholipid Syndrome - blood
Antiphospholipid Syndrome - complications
Antiphospholipid Syndrome - immunology
beta 2-Glycoprotein I - immunology
Cohort Studies
Domain 1
Female
Hematology, Oncology and Palliative Medicine
Humans
Lupus Coagulation Inhibitor - blood
Lupus Coagulation Inhibitor - immunology
Male
Middle Aged
Prognosis
Thrombosis - blood
Thrombosis - complications
Thrombosis - immunology
title Clinical implications of the detection of antibodies directed against domain 1 of β2-glycoprotein 1 in thrombotic antiphospholipid syndrome
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