Detection of Anti-Cardiolipin and Anti-β2glycoprotein I Antibodies Differs between Platforms without Influence on Association with Clinical Symptoms

Walid Chayoua; Hilde Kelchtermans; Gary W. Moore; Jean-Christophe Gris; Jacek Musial; Denis Wahl; Stéphane Zuily; Francesca Gianniello; Pierre Fontana; Jasper Remijn; Rolf T. Urbanus; Bas de Laat; Katrien M. J. Devreese

doi:10.1055/s-0039-1679901

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2019; 119(05): 797-806
DOI: 10.1055/s-0039-1679901

New Technologies, Diagnostic Tools and Drugs

Georg Thieme Verlag KG Stuttgart · New York

Detection of Anti-Cardiolipin and Anti-β2glycoprotein I Antibodies Differs between Platforms without Influence on Association with Clinical Symptoms

Walid Chayoua

¹Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

²Synapse Research Institute, Maastricht, The Netherlands

,

Hilde Kelchtermans

¹Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

²Synapse Research Institute, Maastricht, The Netherlands

,

Gary W. Moore

³Department of Haemostasis and Thrombosis, Viapath Analytics, Guy's & St. Thomas' Hospitals, London, United Kingdom

,

Jean-Christophe Gris

⁴Centre Hospitalier Universitaire de Nîmes et Université de Montpellier, Montpellier, France

⁵Ivan Sechenov First Moscow State Medical University, Moscow, Russia

,

Jacek Musial

⁶2nd Department of Internal Medicine, Jagiellonian University Medical College, Jagiellonian University, Krakow, Poland

,

Denis Wahl

⁷Vascular Medicine Division and Regional Competence Center for Rare Vascular and Systemic Autoimmune Diseases, Centre Hospitalier Regional Universitaire de Nancy, Université de Lorraine, Inserm, DCAC, Nancy, France

,

Stéphane Zuily

⁷Vascular Medicine Division and Regional Competence Center for Rare Vascular and Systemic Autoimmune Diseases, Centre Hospitalier Regional Universitaire de Nancy, Université de Lorraine, Inserm, DCAC, Nancy, France

,

Francesca Gianniello

⁸Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy

,

Pierre Fontana

⁹Division of Angiology and Haemostasis, University Hospital Geneva, University of Geneva, Geneva, Switzerland

,

Jasper Remijn

¹⁰Department of Clinical Chemistry and Hematology, Gelre Hospitals, Apeldoorn, The Netherlands

,

Rolf T. Urbanus

¹¹Department of Clinical Chemistry and Haematology, Center for Circulatory Health, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

,

Bas de Laat

¹Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

²Synapse Research Institute, Maastricht, The Netherlands

,

Katrien M. J. Devreese

¹²Coagulation Laboratory, Department of Diagnostic Sciences, Ghent University Hospital, Ghent University, Ghent, Belgium

› Author Affiliations

Abstract

Background The anti-phospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with persistent presence of anti-phospholipid antibodies (aPL). Laboratory criteria include aPL detection by coagulation tests for lupus anticoagulant (LAC) or solid phase assays measuring anti-β2 glycoprotein I (aβ2GPI) or anti-cardiolipin (aCL) immunoglobulin (Ig) G/IgM antibodies. External quality control programs illustrate that commercially available aPL assays produce variable results.

Objective We aimed to investigate the agreement and diagnostic accuracy of solid phase assays.

Materials and Methods In this multi-centre study, 1,168 patient samples were tested on one site for aCL and aβ2GPI IgG/IgM antibodies by four solid phase test systems. Samples included APS patients, controls and monoclonal antibodies (MoAB) against different epitopes of β2GPI. LAC was determined by the local centre.

Results aCL IgM assays resulted in the most discrepancies (60%), while aCL IgG and aβ2GPI IgM assays resulted in lower discrepancies (36%), suggesting better agreement. Discrepant samples displayed lower median aPL titers. Dependent on the solid phase test system, odds ratios (ORs) for thrombosis and pregnancy morbidity ranged from 1.98 to 2.56 and 3.42 to 4.78, respectively. Three platforms showed lower sensitivity for MoAB directed against the glycine (Gly) 40-arginine (Arg) 43 epitope of domain I of β2GPI.

Conclusion Poor agreement was observed between different commercially available aCL and aβ2GPI IgG/IgM assays, hampering uniformity in the identification of aPL-positive patients. Clinical association was globally concordant between solid phase test systems considering results of the four aPL together. An assay sensitive in detecting the MoAB against Gly40-Arg43 of domain I of β2GPI reached the highest OR for thrombosis.

Keywords

solid phase assays - anti-cardiolipin - β2 glycoprotein I - epitope - thrombosis

Full Text

References

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Supplementary Material

Supplementary Material