Inflammatory myopathies

Mass spectrometry-based identification of new anti-Ly and known antisynthetase autoantibodies

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

CARS1 is the dominant cognate ARS autoantigen of the newly discovered anti-Ly ASA specificity. Rare and common ASA specificities could be detected by both unbiased and targeted IP-MS.

Study context

Population
Individuals with features of antisynthetase syndrome (ASyS), with or without previously detected antisynthetase autoantibodies, plus disease and healthy controls
Participants
5 / 12 / 4
Comparison
ASyS features without antisynthetase autoantibodies (ASAs) vs ASyS features with ASAs vs Healthy controls
  • ASyS features without ASAsn = 5
  • ASyS features with ASAsn = 12
  • Healthy controlsn = 4reference
Outcome
Discovery and detection of ASAs by IP-MS
Methodological detailsunbiased IP-MS discovery, IP-western blot confirmation, targeted IP-MS assay development and validation
  • Unbiased IP-MS discovery
  • IP-western blot confirmation
  • Targeted IP-MS assay development and validation

Main finding

As reported in the abstract

  • Autoantibodies to cytoplasmic cysteinyl-tRNA-synthetase (CARS1) identified by IP-MS and confirmed by western blot as a new ASA specificity, anti-Ly, in a patient with ASyS features
  • Rare ASAs (anti-OJ, anti-Zo, anti-KS) and common ASAs also identified by IP-MS
  • Targeted IP-MS approach for ASA detection developed and validated (known ASAs n=16, disease controls n=20, healthy controls n=25)

Further findings

Targeted IP-MS in additional cohort with multiple ASyS features or isolated myositis without previously detected ASAs (n=26)

One additional patient with anti-OJ autoantibodies identified that were missed by line and dot immunoassays
1

Original publication

Mass spectrometry-based identification of new anti-Ly and known antisynthetase autoantibodies. Ann Rheum Dis. Published 26 December 2022. doi:10.1136/ard-2022-222686

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