PUF60: A prominent new target of the autoimmune response in dermatomyositis and Sjögren's syndrome

David F. Fiorentino, Matthew Presby, Alan N. Baer, Michelle Petri, Kerri E. Rieger, Mark Soloski, Antony Rosen, Andrew L. Mammen, Lisa Christopher-Stine, Livia Casciola-Rosen

Research output: Contribution to journalArticle

Abstract

Objectives Autoantibodies are used clinically to phenotype and subset patients with autoimmune rheumatic diseases. We detected a novel 60 kDa autoantibody specificity by immunoblotting using a dermatomyositis (DM) patient's serum. Our objective was to identify the targeted autoantigen and to evaluate disease specificity and clinical significance of this new autoantibody. Methods A new 60 kDa specificity was detected by immunoblotting HeLa cell lysates. The targeted autoantigen was identified as poly(U)-binding-splicing factor 60 kDa (PUF60) using (i) a human protein array and (ii) two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing. Anti-PUF60 antibodies were assayed by ELISA using sera from patients with primary Sjögren's syndrome (SS; n=84), systemic lupus erythematosus (SLE; n=71), DM (n=267), polymyositis (n=45), inclusion body myositis (n=45) and healthy controls (n=38). Results PUF60 was identified as a new autoantigen.Anti-PUF60 antibodies were present in 25/84 (30%) patients with SS, 6/71 (8.5%) patients with SLE and 2/38 (5.0%) control subjects (SS vs controls, p=0.002; SLE vs controls, p=0.711). Anti-PUF60 antibodies were present in 48/267 (18.0%) patients with DM versus 4/45 (8.9%) and 5/45 (11.1%) patients with inclusion body myositis and polymyositis, respectively. The antibody was significantly associated with anti-Ro52 antibodies, rheumatoid factor and hyperglobulinemia in the patients with primary SS. In patients with DM, the antibody was associated with anti-transcription intermediary factor 1 gamma seropositivity and Caucasian race. Conclusions PUF60 represents a novel autoantigen in patients with SS and DM. PUF60 antibodies are associated with distinct clinical features and different immune responses in different diseases.

Original languageEnglish (US)
Pages (from-to)1145-1151
Number of pages7
JournalAnnals of the rheumatic diseases
Volume75
Issue number6
DOIs
StatePublished - Jun 2016

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this