期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：47
页码：E7526-E7534
DOI：10.1073/pnas.1615990113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceIn this study, we created a barcoded whole-genome ORF mRNA display library and combined it with phage-immunoprecipitation sequencing to look for autoantibodies in sera from patients with scleroderma who also had coincident cancer without a known autoantibody biomarker. Using these two technologies, we found that 25% of these patients had autoantibodies to RNA Binding Region Containing 3 (RNPC3) and multiple other components of the minor spliceosome. There was evidence of intra- and intermolecular epitope spreading within RNPC3 and the complex. These combined technologies are highly effective for rapidly discovering autoantibodies in patient subgroups, which will be useful tools for patient stratification and discovery of pathogenic pathways. 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.
