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Background: Myositis-specific autoantibodies (MSAs) are typically considered mutually exclusive, and multiple positivities using the reference standard, Immunoprecipitation, are increasingly rare. However, other techniques, such as Enzyme-Linked Immunosorbent Assay (ELISA) and Line Blot Immunoassay (LIA), are commonly employed in clinical practice. These assays are cheaper, faster and require less clinical expertise to perform; however, they are associated with rates of multiple positivity and an increased probability of false positivity. Objectives: This study aims to evaluate the real-life prevalence and the clinical meaning of multiple seropositivity for MSA and Myositis Associated Antibodies (MAAs) in the Classification Criteria of Anti-Synthetase Syndrome (CLASS) cohort. Methods: The CLASS Project represents a collaborative, multi-center initiative to develop and validate classification criteria for Anti-synthetase Syndrome (ASSD). This retrospective and prospective study involved 101 centers globally, enrolling 2003 ASSD patients and 2175 controls (ASSD mimickers) from June 2020 to March 2022. Data for the study were collected and managed using Research Electronic Data Capture. From our database, we extracted clinical features and Antinuclear Antibody (ANA) patterns in patients exhibiting positivity for MSA and/or Myositis Associated Antibodies (MAA), excluding anti-Ro52kD (Figure 1). Results: Seropositivity for MSA/MAA was confirmed in 2832 patients (67.8%). Multiple positivities for MSA/MAAs (excluding anti-Ro52kD) were identified in 305/2589 cases (11.8%). Notably, 176/2589 patients (6.8%) exhibited positivity for at least two MSAs. Multiple seropositivity was reported by 69/101 centres, with a single centre contributing to 25.2% of total positive results. ELISA confirmed multiple seropositivity in 134/585 subjects (33.7%), IP in 99/412 (24%), and LIA in 720/1646 (43.7%, p=Conclusion: The utilization of LIA exposes individuals to a recognized risk of false positivity. However, in the CLASS cohort, a substantial contribution of patients was from a single centre. It was noted that there was an absence of an association between anti-PmScl and anti-Mi2 with the anticipated ANA pattern, whether present individually or in combination. Our study demonstrates that MSAs correlated with known clinical associations even in instances of combined positivity. Notably, 7.9% of cases with multiple MSAs exhibited a clinical presentation coherent with all the seropositivity. Our analysis demonstrates the potential existence of overlap syndromes that may be under-recognized in clinical practice. REFERENCES: NIL. Acknowledgements: We are grateful to all members of the CLASS project Disclosure of Interests: Aravinthan Loganathan: None declared, Gianluca Sambataro Boheringer Ingelheim, Akira Yoshida: None declared, Eduardo Dourado: None declared, Giovanni Zanframundo: None declared, Francisca Bozan: None declared, Daphne Rivero Gallegos: None declared, Iazsmin Bauer-Ventura: None declared, Yasuhiko Yamano: None declared, Sangmee Bae: None declared, Darosa Lim: None declared, Sara Faghihi-Kashani: None declared, Francesco Bonella: None declared, Tamera J. Corte: None declared, Tracy Doyle Bayer, David Fiorentino: None declared, Miguel Ángel González-Gay: None declared, Marie Hudson: None declared, Masataka Kuwana Asahi Kasei Parma, Boehringer-Ingelheim, Chugai, Eisai, Janssen, Kissei, Mochida, Nippon Shinyaku, and Ono Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Chugai, GSK, Kissei, and Mochida; Research grants: Boehringer-Ingelheim, MBL, and Ono Pharmaceuticals, Ingrid E. Lundberg: None declared, Andrew Mammen: None declared, Neil McHugh: None declared, Fredrick Miller: None declared, Carlomaurizio Montecucco: None declared, Chester V Oddis: None declared, Jorge Rojas-Serrano: None declared, Jens Schmidt: None declared, Carlo Alberto Scirè: None declared, Albert Selva-O'Callaghan: None declared, Victoria Werth: None declared, Rohit Aggarwal Actigraph, Alexion, ANI Pharmaceuticals, Argenx, AstraZeneca, Boehringer-Ingelheim, Bristol Myers-Squibb, CabalettaBio, Capella Bioscience, Corbus, CSL Behring, EMD Serono, Galapagos, Horizon Therapeutics, I-Cell, Janssen, Kezar, Kyverna, Merck, Novartis, Nuvig Therapeutics, Octapharma, Pfizer, Regeneron, Roivant, Sanofi, Teva, Artsome, Capstanx, Manta, Boehringer Ingelheim, Bristol Myers-Squibb, EMD Serono, Janssen, Mallinckrodt, Pfizer, Q32, Lorenzo Cavagna Boheringer Ingelheim.
Loganathan et al. (Sat,) studied this question.