Measuring IgA Anti-β2-Glycoprotein I and IgG/IgA Anti-Domain I Antibodies Adds Value to Current Serological Assays for the Antiphospholipid Syndrome

Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β2-glycoprotein I (aβ2GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β2GPI,...

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Published inPloS one Vol. 11; no. 6; p. e0156407
Main Authors Pericleous, Charis, Ferreira, Isabel, Borghi, Orietta, Pregnolato, Francesca, McDonnell, Thomas, Garza-Garcia, Acely, Driscoll, Paul, Pierangeli, Silvia, Isenberg, David, Ioannou, Yiannis, Giles, Ian, Meroni, Pier Luigi, Rahman, Anisur
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 02.06.2016
Public Library of Science (PLoS)
Subjects
Adult
Antibodies
Antibodies, Anticardiolipin - blood
Antibodies, Antiphospholipid - immunology
Antibodies, Antiphospholipid - isolation & purification
Antigens
Antiphospholipid antibodies
Antiphospholipid syndrome
Antiphospholipid Syndrome - blood
Antiphospholipid Syndrome - immunology
Antiphospholipid Syndrome - pathology
Arthritis
Assaying
Autoimmune diseases
beta 2-Glycoprotein I - immunology
beta 2-Glycoprotein I - isolation & purification
Biology and Life Sciences
Cardiolipin
Complications
Diagnostic tests
Enzyme-Linked Immunosorbent Assay
Epitopes
Epitopes - immunology
Female
Glycoprotein I
Glycoproteins
Humans
Immunoglobulin A
Immunoglobulin A - immunology
Immunoglobulin G
Immunoglobulin G - immunology
Immunoglobulin M
Immunoglobulins
Laboratories
Lupus
Male
Medical research
Medicine
Medicine and Health Sciences
Middle Aged
Patients
Physical Sciences
Pregnancy
Regression analysis
Research and Analysis Methods
Rheumatology
Serologic Tests
Thrombosis
Thrombosis - blood
Thrombosis - immunology
England
Italy
United Kingdom > UK
United States > US
Online AccessGet full text
ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0156407

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Abstract Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β2-glycoprotein I (aβ2GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β2GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, β2GPI and DI in APS. Serum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, aβ2GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays. All assays displayed good specificity for APS; IgG aCL and IgG aβ2GPI assays however, had the highest sensitivity. Testing positive for IgA aβ2GPI resulted in a higher hazard ratio for APS compared to IgM aβ2GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or aβ2GPI, the presence of aDI raised the hazard ratio for APS by 3-5 fold. IgG aCL, aβ2GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS. Measuring IgG aDI and IgA aβ2GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS.
AbstractList Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β2-glycoprotein I (aβ2GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β2GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, β2GPI and DI in APS.INTRODUCTIONCurrently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β2-glycoprotein I (aβ2GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β2GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, β2GPI and DI in APS.Serum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, aβ2GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays.METHODSSerum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, aβ2GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays.All assays displayed good specificity for APS; IgG aCL and IgG aβ2GPI assays however, had the highest sensitivity. Testing positive for IgA aβ2GPI resulted in a higher hazard ratio for APS compared to IgM aβ2GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or aβ2GPI, the presence of aDI raised the hazard ratio for APS by 3-5 fold. IgG aCL, aβ2GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS.RESULTSAll assays displayed good specificity for APS; IgG aCL and IgG aβ2GPI assays however, had the highest sensitivity. Testing positive for IgA aβ2GPI resulted in a higher hazard ratio for APS compared to IgM aβ2GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or aβ2GPI, the presence of aDI raised the hazard ratio for APS by 3-5 fold. IgG aCL, aβ2GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS.Measuring IgG aDI and IgA aβ2GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS.CONCLUSIONMeasuring IgG aDI and IgA aβ2GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS.
Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β2-glycoprotein I (aβ2GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β2GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, β2GPI and DI in APS. Serum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, aβ2GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays. All assays displayed good specificity for APS; IgG aCL and IgG aβ2GPI assays however, had the highest sensitivity. Testing positive for IgA aβ2GPI resulted in a higher hazard ratio for APS compared to IgM aβ2GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or aβ2GPI, the presence of aDI raised the hazard ratio for APS by 3-5 fold. IgG aCL, aβ2GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS. Measuring IgG aDI and IgA aβ2GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS.
Introduction Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β2-glycoprotein I (aβ2GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β2GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, β2GPI and DI in APS. Methods Serum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, aβ2GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays. Results All assays displayed good specificity for APS; IgG aCL and IgG aβ2GPI assays however, had the highest sensitivity. Testing positive for IgA aβ2GPI resulted in a higher hazard ratio for APS compared to IgM aβ2GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or aβ2GPI, the presence of aDI raised the hazard ratio for APS by 3–5 fold. IgG aCL, aβ2GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS. Conclusion Measuring IgG aDI and IgA aβ2GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS.
IntroductionCurrently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β2-glycoprotein I (aβ2GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β2GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, β2GPI and DI in APS.MethodsSerum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, aβ2GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays.ResultsAll assays displayed good specificity for APS; IgG aCL and IgG aβ2GPI assays however, had the highest sensitivity. Testing positive for IgA aβ2GPI resulted in a higher hazard ratio for APS compared to IgM aβ2GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or aβ2GPI, the presence of aDI raised the hazard ratio for APS by 3-5 fold. IgG aCL, aβ2GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS.ConclusionMeasuring IgG aDI and IgA aβ2GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS.
Introduction Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β 2 -glycoprotein I (aβ 2 GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β 2 GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, β 2 GPI and DI in APS. Methods Serum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, aβ 2 GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays. Results All assays displayed good specificity for APS; IgG aCL and IgG aβ 2 GPI assays however, had the highest sensitivity. Testing positive for IgA aβ 2 GPI resulted in a higher hazard ratio for APS compared to IgM aβ 2 GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or aβ 2 GPI, the presence of aDI raised the hazard ratio for APS by 3–5 fold. IgG aCL, aβ 2 GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS. Conclusion Measuring IgG aDI and IgA aβ 2 GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS.
Author Borghi, Orietta
Garza-Garcia, Acely
Meroni, Pier Luigi
Pierangeli, Silvia
Driscoll, Paul
Ioannou, Yiannis
Pericleous, Charis
Rahman, Anisur
McDonnell, Thomas
Giles, Ian
Ferreira, Isabel
Isenberg, David
Pregnolato, Francesca
AuthorAffiliation 1 Centre for Rheumatology Research, Division of Medicine, University College London, London, United Kingdom
2 Laboratory of Immuno-rheumatology, IRCCS Istituto Auxologico Italiano, Milan, Italy
3 Structural Biology, MRC National Institute for Medical Research, London, United Kingdom
Nippon Medical School Graduate School of Medicine, JAPAN
4 Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America
5 Arthritis Research UK Centre for Adolescent Rheumatology, UCL Hospital and Great Ormond Street Hospital, London, United Kingdom
AuthorAffiliation_xml – name: 3 Structural Biology, MRC National Institute for Medical Research, London, United Kingdom
– name: 4 Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America
– name: 2 Laboratory of Immuno-rheumatology, IRCCS Istituto Auxologico Italiano, Milan, Italy
– name: 1 Centre for Rheumatology Research, Division of Medicine, University College London, London, United Kingdom
– name: Nippon Medical School Graduate School of Medicine, JAPAN
– name: 5 Arthritis Research UK Centre for Adolescent Rheumatology, UCL Hospital and Great Ormond Street Hospital, London, United Kingdom
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/27253369$$D View this record in MEDLINE/PubMed
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DocumentTitleAlternate Comparing Current and Novel Diagnostic Tests for Antiphospholipid Syndrome
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Conceived and designed the experiments: CP YI IG AR. Performed the experiments: CP. Analyzed the data: CP. Contributed reagents/materials/analysis tools: IF OB FP TM AG PD SP DI PLM. Wrote the paper: CP AR.
Competing Interests: The authors have declared that no competing interests exist.
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Snippet Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β2-glycoprotein I...
Introduction Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and...
IntroductionCurrently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and...
Introduction Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β 2...
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StartPage e0156407
SubjectTerms Adult
Antibodies
Antibodies, Anticardiolipin - blood
Antibodies, Antiphospholipid - immunology
Antibodies, Antiphospholipid - isolation & purification
Antigens
Antiphospholipid antibodies
Antiphospholipid syndrome
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Title Measuring IgA Anti-β2-Glycoprotein I and IgG/IgA Anti-Domain I Antibodies Adds Value to Current Serological Assays for the Antiphospholipid Syndrome
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