Clinical Characteristics of Anti‐synthetase Syndrome: Analysis From the Classification Criteria for Anti‐Synthetase Syndrome Project
Authors: Faghihi‐Kashani Sara , Yoshida Akira , Bozan Francisca , Zanframundo Giovanni , Rozza Davide , Loganathan Aravinthan , Dourado Eduardo , Sambataro Gianluca , Bauer‐Ventura Iazsmin , Bae Sangmee Sharon , Lim Darosa , Rivero‐Gallegos Daphne , Yamano Yasuhiko , Selva‐O'Callaghan Albert , Mammen Andrew L. , Scirè Carlo A. , Montecucco Carlomaurizio , Oddis Chester V. , Fiorentino David , Bonella Francesco , Miller Frederick W. , Lundberg Ingrid E. , Schmidt Jens , Rojas‐Serrano Jorge , Hudson Marie , Kuwana Masataka , González‐Gay Miguel Angel , McHugh Neil , Corte Tamera J. , Doyle Tracy Jennifer , Werth Victoria P. , Gupta Latika , Perez Roman Diana Isabel , Bianchessi Lorenzo M. , Devarasetti Phani Kumar , Shinjo Samuel Katsuyuki , Luppi Fabrizio , Cavazzana Ilaria , Moghadam‐Kia Siamak , Fornaro Marco , Volkmann Elizabeth R. , Piga Matteo , Loarce‐Martos Jesus , De Luca Giacomo , Knitza Johannes , Wolff‐Cecchi Veronica , Sebastiani Marco , Schiffenbauer Adam , Rider Lisa G. , Campanilho‐Marques Raquel , Marts Lucian , Bravi Elena , Gunawardena Harsha , Aggarwal Rohit , Cavagna Lorenzo ,   the Classification Criteria for Anti‐Synthetase Syndrome Project participating investigators
Published: October 2024

Objective

Anti‐synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data‐driven classification criteria for ASSD.

Methods

We used a large, international, multicenter “Classification Criteria for Anti‐synthetase Syndrome” (CLASS) project database, which includes both patients with ASSD and controls with mimicking conditions, namely, SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort.

Results

Our analysis included 948 patients with ASSD and 1,077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in patients with ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo‐1 and non–Jo‐1 anti‐synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti‐Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/magnetic resonance imaging/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between patients with ASSD and controls or were inversely associated with ASSD.

Conclusion

We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data‐driven classification criteria for ASSD.

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