Identification of a Novel Autoantigen Eukaryotic Initiation Factor 3 Associated with Polymyositis

Research output: Contribution to journalArticle

  • External authors:
  • Zoë E. Betteridge
  • J. Vencovsky
  • John Winer
  • Kiran K. Putchakayala
  • I. Lundberg
  • K. Danko
  • R. G. Cooper
  • NJ McHugh

Abstract

Objectives: To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis.
Methods: Sera or plasma from 678 polymyositis (PM) patients were analysed for autoantigen specificity by radio-labelled protein-immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by in-direct immunofluorescence (IIF) and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with dermatomyositis (DM) (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren’s syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls.
Results: IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease specific or healthy control sera. IIF demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass Spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3 positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment.
Conclusions: We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

Bibliographical metadata

Original languageEnglish
JournalRheumatology (Oxford)
Publication statusAccepted/In press - 6 Aug 2019

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