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Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7526-E7534. Epub 2016 Nov 7.

Systematic autoantigen analysis identifies a distinct subtype of scleroderma with coincident cancer.

Xu GJ1,2,3,4,5, Shah AA6, Li MZ3,4,5, Xu Q3,4,5, Rosen A6, Casciola-Rosen L7, Elledge SJ8,4,5.

Author information

1
Program in Biophysics, Harvard University, Cambridge, MA 02115.
2
Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Cambridge, MA 02139.
3
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
4
Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115.
5
Department of Genetics, Program in Virology, Harvard University Medical School, Boston, MA 02115.
6
Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
7
Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224 selledge@genetics.med.harvard.edu lcr@jhmi.edu.
8
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115; selledge@genetics.med.harvard.edu lcr@jhmi.edu.

Abstract

Scleroderma is a chronic autoimmune rheumatic disease associated with widespread tissue fibrosis and vasculopathy. Approximately two-thirds of all patients with scleroderma present with three dominant autoantibody subsets. Here, we used a pair of complementary high-throughput methods for antibody epitope discovery to examine patients with scleroderma with or without known autoantibody specificities. We identified a specificity for the minor spliceosome complex containing RNA Binding Region (RNP1, RNA recognition motif) Containing 3 (RNPC3) that is found in patients with scleroderma without known specificities and is absent in unrelated autoimmune diseases. We found strong evidence for both intra- and intermolecular epitope spreading in patients with RNA polymerase III (POLR3) and the minor spliceosome specificities. Our results demonstrate the utility of these technologies in rapidly identifying antibodies that can serve as biomarkers of disease subsets in the evolving precision medicine era.

KEYWORDS:

PLATO; PhIP-Seq; autoimmunity; systemic sclerosis

PMID:
27821747
PMCID:
PMC5127349
DOI:
10.1073/pnas.1615990113
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest.

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