Abstract
Objectives
No reference data are available on repositories to measure precision of autoantibody assays. The scope of this study was to document inter- and intra-run variations of quantitative autoantibody assays based on a real-world large international data set.
Methods
Members of the European Autoimmunity Standardisation Initiative (EASI) group collected the data of intra- and inter-run variability obtained with assays quantifying 15 different autoantibodies in voluntary participating laboratories from their country. We analyzed the impact on the assay performances of the type of immunoassay, the number of measurements used to calculate the coefficient of variation (CVs), the nature and the autoantibody level of the internal quality control (IQC).
Results
Data were obtained from 64 laboratories from 15 European countries between February and October 2021. We analyzed 686 and 1,331 values of intra- and inter-run CVs, respectively. Both CVs were significantly dependent on: the method of immunoassay, the level of IQC with higher imprecision observed when the antibody levels were lower than 2-fold the threshold for positivity, and the nature of the IQC with commercial IQCs having lower CVs than patients-derived IQCs. Our analyses also show that the type of autoantibody has low impact on the assay’ performances and that 15 measurements are sufficient to establish reliable intra- and inter-run variations.
Conclusions
This study provides for the first time an international repository yielding values of intra- and inter-run variation for quantitative autoantibody assays. These data could be useful for ISO 15189 accreditation requirements and will allow clinical diagnostic laboratories to assure quality of patient results.
Funding source: Fondazione IRCCS Policlinico San Matteo
Award Identifier / Grant number: Unassigned
Funding source: Università degli Studi di Firenze
Award Identifier / Grant number: Unassigned
Funding source: University of Thessaly
Award Identifier / Grant number: Unassigned
Funding source: KU Leuven
Award Identifier / Grant number: Unassigned
Funding source: Vrije Universiteit Amsterdam
Award Identifier / Grant number: Unassigned
Acknowledgments
Participating centers: We thank all physicians, biologists and scientists from the participating DBL for sharing their data: Marie Senant Private Biomedical Laboratory Cerballiance, Lisses, France; Laurence Guis-Cabanne Private Biomedical Laboratory Biomnis-Eurofins, Ivry, France; Georges Chyderiotis Laboratory Biomnis-Eurofins Lyon, France; Pascale Ghillani-Dalbin, Laboratory of Immunology, Hospital Pitie-Salpetriere, Paris, France; Chantal Dumestre-Perard, Laboratory of Immunology, University Hospital of Grenoble, Grenoble, France; Marie-Agnès Dragon-Durey, Laboratory of Immunology, Hospital Georges Pompidou, Paris, France; Nicole Fabien, Laboratory of Immunology, University Hospital of Lyon, France; Marie-Alexandra Alyanakian, Laboratory of Immunology, Hospital Necker Enfants Malades, Paris, France; Claudia Alpini, Servizio Analisi Chimico-Cliniche, Fondazione IRCCS Policlinico San Matteo,Pavia, Italy; Antonio Antico and Maria-Piera Panozzo, Lab Analisi ULSS 4, Santorso (VI), Italy; Gabriella Baldi, Laboratorio di Endocrinologia, Dipartimento di Medicina di Laboratorio, Ospedale Sacco, Polo Universitario, ASST Fatebenefratelli Sacco, Milano, Italy; Teresa Carbone, UOC Patologia Clinica, ASM, Matera, Italy;Sergio Finazzi, Laboratorio Analisi, ASST Ovest Milanese, Legnano, Italy; Franco Franceschini, Dipartimento di Scienze Cliniche e Sperimentali, Università di Brescia and Reumatologia e Immunologia Clinica, ASST Spedali Civili, Brescia, Italy; Nicoletta Gallo, Azienda Ospedaliera Università di Padova, Dipartimento Strutturale Medicina di Laboratorio, UOC Medicina di Laboratorio, Padova, Italy; Emirena Garrafa and Duilio Brugnoni, Dipartimento di Diagnostica di Laboratorio, ASST, Spedali Civili, Brescia, Italy; Maria Infantino e Mariangela Manfredi, Laboratorio Immunologia Allergologia, Dipartimento di Medicina di Laboratorio, Ospedale San Giovanni di Dio Azienda, Usl Toscana Centro, Firenze, Italy; Magda Marchese, Servizio di Patologia Clinica, Ospedale Santa Maria Delle Grazie-Asl Napoli two Nord, Napoli, Italy; Boaz Palterer and Paola Parronchi, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; Giampaola Pesce, Laboratorio Diagnostico di Autoimmunologia, IRCCS Ospedale Policlinico San Martino, and Dipartimento di Medicina Interna e specialità mediche (DIMI), Università di Genova, Genova, Italy; Amelia Rigon, Luisa Arcarese and Roberto Giacomelli, UOC di Immunologia Clinica e Reumatologia, Università Campus Bio-Medico, Roma, Italy; Maria-Cristina Sacchi, Laboratorio Analisi, Alessandria, Italy; Michela Tonegato, Sara Ghisellini and Michela Boni, Laboratorio Unico Provinciale Dipartimento Biotecnologie, Trasfusionale e di Laboratorio, Azienda Ospedaliero-Universitaria S. Anna, Cona (FE), Italy; Maria-Teresa Trevisan, Laboratorio, Ospedale G. Fracastoro, Verona, Italy; Danilo Villalta, Allergologia e Immunologia clinica, Presidio Ospedaliero S. Maria degli Angeli, Pordenone, Italy; Dr Liaskos, Dr Patrikiou Laboratory of Rheumatology and Clinical Immunology, University of Thessaly, Larissa, Greece; Hristina Andreeva, Section of Protein, Allergy and Immunology, Laboratory Medicine Department, Diagnostic Clinic, University Hospital of North Norway, Tromsø, Norway; Carina Strøm, Section of Protein, Allergy and Immunology, Laboratory Medicine Department, Diagnostic Clinic, University Hospital of North Norway, Tromsø, Norway; Sølvi Fagervik, Department of Laboratory Medicine, Nordland Hospital Trust, Bodø, Norway; Christine Torsvik Steinsvåg, Department for Immunology and Transfusion medicine, Sørlandet sykehus HF, Kristiansand, Norway Livia Bajelan, Autoantibodies Diagnostics, Section for medical immunology, Department for immunology and transfusion medicine, Oslo University Hospital, Nydalen, Oslo, Norway; Noemie Taer, Section for Medical Immunology, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway; Kristine Thomassen Berget, Department for immunology and transfusion medicine, Sørlandet sykehus HF, Kristiansand, Norway; Carolien Bonroy, Department of Diagnostic Sciences, Ghent University; Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Xavier Bossuyt, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium and Department of Laboratory Medicine, University Hospitals Leuven, Belgium; Sofie Schouwers, Department of Laboratory Medicine, GZA Hospitals, Antwerp, Belgium; Laurence Lutteri, Department of Clinical Chemistry, University Hospital Liège, Liège, Belgium; Martine Vercammen, Department of Laboratory Medicine, AZ Saint-Jan Hospital Bruges-Ostend, Bruges, Belgium; Lieve Van Hoovels, Department of Laboratory Medicine, OLV Aalst, Belgium; Ana Kozmar, Department of Laboratory Diagnostics, University Hospital Center Zagreb, Croatia; Lovorka Đerek, Clinical Department of Laboratory Diagnostics, University Hospital Dubrava, Zagreb, Croatia; Lora Dukić, Department of medical laboratory diagnostics, University Hospital Sveti Duh, Zagreb, Croatia; Vedrana Drvar, Clinical Department of Laboratory Diagnostics, Clinical Hospital Center Rijeka, Croatia; Ines Šahinović, Clinical Department of Laboratory Diagnostics, Clinical Hospital Center Osijek, Croatia; Tímea Berki, Department of Immunology and Biotechnology, University of Pécs, Medical School, Pécs, Hungary; Eszter Nagy, National Institute of Locomotor Diseases and Disabilities, Budapest and Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary; Gábor Nagy and Péter Antal-Szalmás, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Zsuzsanna Beleznay, Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary; Liisa Kuhi, Central Laboratory, Diagnostic Clinic, East Tallinn Central Hospital, Tallinn, Estonia; Maiga Mägi, Clinical Immunology Department, Laboratory, North Estonia Medical Centre (SA Põhja-Eesti Regionaalhaigla), Tallinn, Estonia; Maarit Veski, Laboratory of Immunology, Central Laboratory, East Tallinn Central Hospital (AS Ida-Tallinna Keskhaigla), Tallinn, Estonia; Irina Golovljova, Laboratory, Tallinn Children´s Hospital (SA Tallinna Lastehaigla), Tallinn, Estonia; Irina Utenko, SYNLAB Eesti OÜ, Estonia; Thorsten Krieger, MVZ Rheumatologie und Autoimmunmedizin GmbH, Hamburg, Germany; Ulrich Sack, Medical Faculty, Institute of Clinical Immunology, University Leipzig, Leipzig, Germany; Manfred Herold, Rheumatology Laboratory, Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria; Rille Pullerits, Department of Clinical immunology, Sahlgrenska University Hospital, Gothenburg, Sweden; Rui Da Silva Rodrigues, Department of Clinical Immunology, Karolinska University Hospital, Stockholm, Sweden; Charlotte Dahle, Clinical Immunology, University Hospital Linkoping, Sweden; Catharina Eriksson, Department of Clinical Microbiology, Division of Infection and Immunology, Umeå University, Umeå, Sweden; Hetty Bontkes, Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Jan Damoiseaux, Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands; Renate van der Molen, Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands; Henny Otten, Laboratory Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Caroline Roozendaal, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Marco Schreurs, Department of Immunology, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands; Vincent Aubert, Service of Immunology and Allergology, Lausanne University Hospital, Lausanne, Switzerland; Luca Bernasconi, Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland; Pascale Bruyère-Cerdan, Laboratory of Clinical Immunology and Allergy, University Hospital Geneva, Geneva, Switzerland; Ingmar Heijnen, Medical Immunology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland; Elisabeth Probst-Müller, Clinic of Immunology, University Hospital Zurich, Zurich, Switzerland; Andrea Griesmacher, Central Institute of Clinical and Chemical Laboratory Diagnostics, University Hospital of Innsbruck, Austria; Werner Klotz, Rheumatology Laboratory, Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria; Lorna Taylor, Department of Immunology, Black Country Pathology Services, West Midlands, United Kingdom.
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Research funding: None declared.
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Author contributions: Marie-Agnes Dragon-Durey collected and analyzed the data with Marie Senant. All authors provided raw data for analyses by collecting data of the national EASI teams, participated in the design of the study, the drafting of the manuscript and provided approval of the final submitted version. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: M-A Dragon-Durey reports speaker fees from Werfen outside the submitted work. N Bizzaro declares lecture fees from Werfen/Inova and ThermoFisher outside the present work. U Sack reports COI not related to this work: lectures for Thermofisher. X Bossuyt reports COI not related to the work: scientific advisory committee Werfen and lecture fee Thermo Fisher. L Musset reports COI as scientific advisor Committee from Werfen and ThermoScientific not related to the present work. M Lopez-Hos reports COI as scientific advisor Committee from Werfen and ThermoScientific not related to the present work. J Damoiseaux reports consultancy fees from Werfen/Inova and ThermoFisher, and speaker fees from ThermoFisher outside the submitted work. M Senant, T Berki, C Bonroy, H Andreeva, D P Bogdanos, C Eriksson, N. Fabien, I Heijnen, M Herold, C Roozendaal, L Kuhi, T Sundic, L Taylor, A Tesija Kuna report no competing interests to declare for this manuscript.
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Informed consent: Not applicable.
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Ethical approval: Not applicable.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0411).
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