Phage Immunoprecipitation‐Sequencing Reveals CDHR5 Autoantibodies in Select Patients With Interstitial Lung Disease

Author:

Upadhyay Vaibhav1ORCID,Yoon Young me2,Vazquez Sara E.3,Velez Tania E.4,Jones Kirk D.1,Lee Cathryn T.2,Law Christopher S.1,Wolters Paul J.1,Lee Seoyeon1,Yang Monica M.1ORCID,Farrand Erica1,Noth Imre5,Strek Mary E.2,Anderson Mark S.1,DeRisi Joseph L.3,Sperling Anne I.4,Shum Anthony K.1ORCID

Affiliation:

1. University of California San Francisco

2. University of Chicago, Illinois

3. University of California San Francisco and Chan Zuckerberg Biohub

4. University of Chicago, Illinois, and University of Virginia Charlottesville

5. University of Virginia Charlottesville

Abstract

ObjectiveInterstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases. Establishing autoimmunity in ILD impacts prognosis and treatment. Patients with ILD are screened for autoimmunity by measuring antinuclear autoantibodies, rheumatoid factors, and other nonspecific tests. However, this approach may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD.MethodsWe use Phage Immunoprecipitation‐Sequencing (PhIP‐Seq) to conduct an autoantibody discovery screen of patients with ILD and controls. We screened for novel autoantigen candidates using PhIP‐Seq. We next developed a radio‐labeled binding assay and validated the leading candidate in 398 patients with ILD recruited from two academic medical centers and 138 blood bank individuals that formed our reference cohort.ResultsPhIP‐Seq identified 17 novel autoreactive targets, and machine learning classifiers derived from these targets discriminated ILD serum from controls. Among the 17 candidates, we validated CDHR5 and found CDHR5 autoantibodies in patients with rheumatologic disorders and importantly, patients not previously diagnosed with autoimmunity. Using survival and transplant free–survival data available from one of the two centers, patients with CDHR5 autoantibodies showed worse survival compared with other patients with connective tissue disease ILD.ConclusionWe used PhIP‐Seq to define a novel CDHR5 autoantibody in a subset of select patients with ILD. Our data complement a recent study showing polymorphisms in the CDHR5‐IRF7 gene locus strongly associated with titer of anticentromere antibodies in systemic sclerosis, creating a growing body of evidence suggesting a link between CDHR5 and autoimmunity.

Funder

Pulmonary Fibrosis Foundation

National Heart, Lung, and Blood Institute

National Institute of Allergy and Infectious Diseases

American Heart Association

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3