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Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank. Clinical and experimental rheumatology Loganathan, A., Zanframundo, G., Yoshida, A., Faghihi-Kashani, S., Bauer Ventura, I., Dourado, E., Bozan, F., Sambataro, G., Yamano, Y., Bae, S. S., Lim, D., Ceribelli, A., Isailovic, N., Selmi, C., Fertig, N., Bravi, E., Kaneko, Y., Saraiva, A. P., 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, T. J., Doyle, T. J., Fiorentino, D., Gonzalez-Gay, M. A., Hudson, M., Kuwana, M., Lundberg, I. E., Mammen, A. L., McHugh, N. J., Miller, F. W., Montecucco, C., Oddis, C. V., Rojas-Serrano, J., Schmidt, J., Scire, C. A., Selva-O'Callaghan, A., Werth, V. P., Alpini, C., Bozzini, S., Cavagna, L., Aggarwal, R., Classification Criteria of Anti-Synthetase Syndrome project biobank, Agarwal, V., Fornaro, M., Alberti, M. L., Needham, M., Houssiau, F., Shinjo, S., Basharat, P., Wang, Q., Quintana, G., Gallay, L., Ebstein, E., Fiehn, C., Feist, E., Schneider, M., Drott, U., Voll, R. E., Danko, K., Shobha, V., Rajasekhar, L., Danieli, M. G., Limonta, M., Matucci-Cerinic, M., Emmi, G., Parronchi, P., Bargagli, E., Maggi, L., Sebastiani, M., Pesci, A., Sainaghi, P. P., Bartolobi-Bocci, E., Barsotti, S., Nakashima, R., Pipitone, N., Riccieri, V., Sebastiani, G., Scarpato, S., Cantarini, L., Berti, A., Colombelli, P. L., Tomietto, P., Lomater, C., Quartuccio, L., Orsolini, G., Kondo, Y., Kimura, N., Vazquez-Del Mercado, M., Andersson, H., Cabral de Fonseca, J. E., Prieto-Gonzalez, S., Greco Merino, M. G., Castaneda, S., Barrio, J. M., Nuno, L., Pinto, I. R., Alen, J. C., Saez-Comet, L., Cagnotto, G., Alpsoy, E., Chinoy, H., Schiopu, E., Gandiga, P., Dimachkie, M., Charles-Schoeman, C., Wilfong, E., Marder, G., Gunawardena, H., Ghetie, D. 2024; 42 (2): 277-287

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 kappa 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.

View details for DOI 10.55563/clinexprheumatol/s14zq8

View details for PubMedID 38488094