Defining anti-synthetase syndrome: a systematic literature review

Giovanni Zanframundo, Sara Faghihi-Kashani, Carlo Alberto Scirè, Francesco Bonella, Tamera J Corte, Tracy J Doyle, David Fiorentino, Miguel A Gonzalez-Gay, Marie Hudson, Masataka Kuwana, Ingrid E Lundberg, Andrew Mammen, Neil McHugh, Frederick W Miller, Carlomaurizio Monteccucco, Chester V Oddis, Jorge Rojas-Serrano, Jens Schmidt, Albert Selva-O'Callaghan, Victoria P WerthGarifallia Sakellariou, Rohit Aggarwal, Lorenzo Cavagna

Research output: Contribution to journalArticlepeer-review

20 Citations (SciVal)


OBJECTIVES: Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance.

METHODS: We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate.

RESULTS: We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly.

CONCLUSIONS: The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.

Original languageEnglish
Pages (from-to)309-319
Number of pages11
JournalClinical and Experimental Rheumatology
Issue number2
Publication statusPublished - 25 Feb 2022


  • Autoantibodies
  • Humans
  • Ligases
  • Syndrome


Dive into the research topics of 'Defining anti-synthetase syndrome: a systematic literature review'. Together they form a unique fingerprint.

Cite this