An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacy

Background: Autoantibodies detection in ANA-associated rheumatic diseases (AARD) is not only used for diagnostic and classification purposes, but also for monitoring. In case of AARD it is questioned if repeated anti-ENA testing is of any substantial value. In this international multicenter retrospe...

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Main Authors: Wim H.M. Vroemen, Maria Infantino, Mariangela Manfredi, Joyce J.B.C. van Beers, Carolien Bonroy, Jan G.M.C. Damoiseaux
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:Journal of Translational Autoimmunity
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589909025000334
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author Wim H.M. Vroemen
Maria Infantino
Mariangela Manfredi
Joyce J.B.C. van Beers
Carolien Bonroy
Jan G.M.C. Damoiseaux
author_facet Wim H.M. Vroemen
Maria Infantino
Mariangela Manfredi
Joyce J.B.C. van Beers
Carolien Bonroy
Jan G.M.C. Damoiseaux
author_sort Wim H.M. Vroemen
collection DOAJ
description Background: Autoantibodies detection in ANA-associated rheumatic diseases (AARD) is not only used for diagnostic and classification purposes, but also for monitoring. In case of AARD it is questioned if repeated anti-ENA testing is of any substantial value. In this international multicenter retrospective study, repeated anti-ENA testing according to local AARD testing algorithms was investigated. Methods: Anti-ENA results (anti-SSA60, -Ro52, -SSB, -Scl-70, -CENP-B, -RNP, -Sm) over a 6 to 10-year period were extracted from the laboratory information systems of three participating centers. Time between repeated testing was determined and concordance analysis was performed. Results: The study included 28557 anti-ENA requests from 19388 patients (72 % female). In 15227 patients (78.5 %) only one anti-ENA test was performed (79.9 % negative), while 4161 patients (21.5 %) underwent multiple (median [interquartile range (IQR)]; 2 [2–4]) tests with a maximum of 31 tests. The median [IQR] time interval between anti-ENA testing for the total cohort was 364 [195–539] days. Concordance analysis demonstrated that repeated anti-ENA test results did not show any change in 3583 patients (86.1 %). Additional autoantibodies were observed in 243 patients (5.8 %). In 76 (1.8 %) patients a positive anti-ENA test was obtained after an initial negative anti-ENA test result, while in 167 (4.0 %) patients additional autoantibodies were detected after an initial positive anti-ENA result. Conclusions: Repeated anti-ENA testing with a median time interval of about one year is common independently of local laboratory testing algorithms, but showed a limited added value since only 1.8 % of the patients have demonstrated a positive anti-ENA test after an initial negative anti-ENA test. These data at least suggest that repeated anti-ENA tests should be discouraged and only be instigated by a change in clinical manifestations.
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spelling doaj-art-ca7337777b02443cb2e67ea5f98972aa2025-08-20T03:24:04ZengElsevierJournal of Translational Autoimmunity2589-90902025-12-011110029810.1016/j.jtauto.2025.100298An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacyWim H.M. Vroemen0Maria Infantino1Mariangela Manfredi2Joyce J.B.C. van Beers3Carolien Bonroy4Jan G.M.C. Damoiseaux5Central Diagnostic Laboratory, Maastricht University Medical Center+, Maastricht, The NetherlandsImmunology and Allergology Laboratory, S. Giovanni di Dio Hospital, Florence, ItalyImmunology and Allergology Laboratory, S. Giovanni di Dio Hospital, Florence, ItalyCentral Diagnostic Laboratory, Maastricht University Medical Center+, Maastricht, The NetherlandsDepartment of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Science, Ghent University, Ghent, BelgiumCentral Diagnostic Laboratory, Maastricht University Medical Center+, Maastricht, The Netherlands; Corresponding author. Central Diagnostic Laboratory, Maastricht University Medical Center+, P. Debyelaan 25. 6229 HX, Maastricht, The Netherlands.Background: Autoantibodies detection in ANA-associated rheumatic diseases (AARD) is not only used for diagnostic and classification purposes, but also for monitoring. In case of AARD it is questioned if repeated anti-ENA testing is of any substantial value. In this international multicenter retrospective study, repeated anti-ENA testing according to local AARD testing algorithms was investigated. Methods: Anti-ENA results (anti-SSA60, -Ro52, -SSB, -Scl-70, -CENP-B, -RNP, -Sm) over a 6 to 10-year period were extracted from the laboratory information systems of three participating centers. Time between repeated testing was determined and concordance analysis was performed. Results: The study included 28557 anti-ENA requests from 19388 patients (72 % female). In 15227 patients (78.5 %) only one anti-ENA test was performed (79.9 % negative), while 4161 patients (21.5 %) underwent multiple (median [interquartile range (IQR)]; 2 [2–4]) tests with a maximum of 31 tests. The median [IQR] time interval between anti-ENA testing for the total cohort was 364 [195–539] days. Concordance analysis demonstrated that repeated anti-ENA test results did not show any change in 3583 patients (86.1 %). Additional autoantibodies were observed in 243 patients (5.8 %). In 76 (1.8 %) patients a positive anti-ENA test was obtained after an initial negative anti-ENA test result, while in 167 (4.0 %) patients additional autoantibodies were detected after an initial positive anti-ENA result. Conclusions: Repeated anti-ENA testing with a median time interval of about one year is common independently of local laboratory testing algorithms, but showed a limited added value since only 1.8 % of the patients have demonstrated a positive anti-ENA test after an initial negative anti-ENA test. These data at least suggest that repeated anti-ENA tests should be discouraged and only be instigated by a change in clinical manifestations.http://www.sciencedirect.com/science/article/pii/S2589909025000334ANA-Associated rheumatic diseasesExtractable nuclear antigen antibodiesLaboratory algorithms
spellingShingle Wim H.M. Vroemen
Maria Infantino
Mariangela Manfredi
Joyce J.B.C. van Beers
Carolien Bonroy
Jan G.M.C. Damoiseaux
An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacy
Journal of Translational Autoimmunity
ANA-Associated rheumatic diseases
Extractable nuclear antigen antibodies
Laboratory algorithms
title An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacy
title_full An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacy
title_fullStr An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacy
title_full_unstemmed An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacy
title_short An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacy
title_sort international multicenter retrospective analysis of repeated anti ena testing in ana associated rheumatic diseases a data driven proposal to increase testing efficacy
topic ANA-Associated rheumatic diseases
Extractable nuclear antigen antibodies
Laboratory algorithms
url http://www.sciencedirect.com/science/article/pii/S2589909025000334
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