TY - JOUR
T1 - PUF60
T2 - A prominent new target of the autoimmune response in dermatomyositis and Sjögren's syndrome
AU - Fiorentino, David F.
AU - Presby, Matthew
AU - Baer, Alan N.
AU - Petri, Michelle
AU - Rieger, Kerri E.
AU - Soloski, Mark
AU - Rosen, Antony
AU - Mammen, Andrew L.
AU - Christopher-Stine, Lisa
AU - Casciola-Rosen, Livia
N1 - Funding Information:
These studies were supported by NIH grants R56A062615 (LCR, DF), R01-AR-44684 (LC-R), R01 DE12354-15A1 (AR) and RO1-AR 43727 (MP). ANB and LC-R's work was additionally supported by the Jerome L. Greene Foundation and the Dorothy and Donald Stabler Foundation. ALM's work was supported (in part) by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. LC-S's work and The Johns Hopkins Myositis Cohort is supported by the Huayi and Siuling Zhang Discovery Fund. The Johns Hopkins Rheumatic Disease Research Core Center, where the assays were performed, is supported by the NIH (grant P30-AR-053503).
PY - 2016/6
Y1 - 2016/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84940183291&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940183291&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2015-207509
DO - 10.1136/annrheumdis-2015-207509
M3 - Article
C2 - 26253095
AN - SCOPUS:84940183291
SN - 0003-4967
VL - 75
SP - 1145
EP - 1151
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 6
ER -