Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank

Loganathan A, Zanframundo G, Yoshida A, Faghihi-Kashani S, Ventura IB, Dourado E, Bozan F, Sambataro G, Yamano Y, Bae SS, Lim D, Ceribelli A, Isailovic N, Selmi C, Fertig N, Bravi E, Kaneko Y, Saraiva AP, Jovani V, Bachiller-Corral J, Cifrian J, Mera-Varela A, Moghadam-Kia S, Wolff V, Campagne J, Meyer A, Giannini M, Triantafyllias K, Knitza J, Gupta L, Molad Y, Iannone F, Cavazzana I, Piga M, De Luca G, Tansley S, Bozzalla-Cassione E, Bonella F, Corte TJ, Doyle TJ, Fiorentino D, Gonzalez-Gay MA, Hudson M, Kuwana M, Lundberg IE, Mammen AL, McHugh NJ, Miller FW, Montecucco C, Oddis CV, Rojas-Serrano J, Schmidt J, Scirè CA, Callaghan ASO, Werth VP, Alpini C, Bozzini S, Cavagna L, Aggarwal R (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 42

Pages Range: 277-287

Journal Issue: 2

DOI: 10.55563/clinexprheumatol/s14zq8

Abstract

OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. METHODS: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient. RESULTS: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. CONCLUSIONS: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Authors with CRIS profile

Involved external institutions

Università degli Studi di Pavia Italy (IT) University of Milano-Bicocca / Università degli Studi di Milano-Bicocca, UNIMIB Italy (IT) Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona Spain (ES) Veterans Health Administration (VHA) United States (USA) (US) Policlinico San Matteo Pavia Fondazione IRCCS Italy (IT) University of Pittsburgh United States (USA) (US) Stanford University United States (USA) (US) University of Chicago United States (USA) (US) Centro Hospitalar do Baixo Vouga Portugal (PT) Hospital Clínico de la Universidad de Chile (HCUCH) Chile (CL) Università degli Studi di Catania Italy (IT) Tosei General Hospital / 公立陶生病院 Japan (JP) University of California Los Angeles (UCLA) United States (USA) (US) Humanitas University Italy (IT) Humanitas Research Hospital / IRCCS Istituto Clinico Humanitas Italy (IT) Ospedale Guglielmo da Saliceto Italy (IT) Keio University Japan (JP) Centro Hospitalar e Universitário de Coimbra (CHUC) Portugal (PT) Hospital General Universitario de Alicante Spain (ES) Hospital Universitario Ramón y Cajal Spain (ES) Marqués de Valdecilla University Hospital / Hospital Universitario de Marqués de Valdecilla (HUMV) Spain (ES) Complejo Hospitalario Universitario de Santiago de Compostela Spain (ES) Hospital del Tórax / Instituto Nacional del Tórax Chile (CL) Hôpital Belle-Isle France (FR) Hôpitaux universitaires de Strasbourg (HUS) / University Hospital Strasbourg France (FR) Royal National Hospital for Rheumatic Diseases United Kingdom (GB) Instituto Nacional de Enfermedades Respiratorias Mexico (MX) Georg-August-Universität Göttingen Germany (DE) Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS) India (IN) Tel Aviv University Israel (IL) University of Bari Aldo Moro / Università degli Studi di Bari Aldo Moro Italy (IT) Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia Italy (IT) Azienda Ospedaliera Universitaria di Cagliari Italy (IT) Università Vita-Salute San Raffaele (UniSR) Italy (IT) Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH Germany (DE) University of Sydney (USYD) Australia (AU) Harvard University United States (USA) (US) Universidad de Cantabria (UC) Spain (ES) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) United States (USA) (US) University of Bath United Kingdom (GB) National Institute of Environmental Health Sciences (NIEHS) United States (USA) (US) Karolinska Institute Sweden (SE)

How to cite

APA:

Loganathan, A., Zanframundo, G., Yoshida, A., Faghihi-Kashani, S., Ventura, I.B., Dourado, E.,... Aggarwal, R. (2024). Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank. Clinical and Experimental Rheumatology, 42(2), 277-287. https://doi.org/10.55563/clinexprheumatol/s14zq8

MLA:

Loganathan, A., et al. "Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank." Clinical and Experimental Rheumatology 42.2 (2024): 277-287.

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