Evidence map›Paper›PMID 38952015›Full record

ArticleACR open rheumatology2024

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

Vaibhav Upadhyay, Young Me Yoon, Sara E Vazquez, Tania E Velez, Kirk D Jones, Cathryn T Lee, Christopher S Law, Paul J Wolters, Seoyeon Lee, Monica M Yang and 7 more

Abstract read
In one paragraph

Article in ACR open rheumatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. To B or Not to B: Germinal Center Responses in Progressive Fibrotic Interstitial Lung Disease.American journal of respiratory and critical care medicine · 2025
    Article
  3. T Regulatory Mechanisms in Airway and Interstitial Lung Disease.Seminars in respiratory and critical care medicine · 2025
    Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Vaibhav UpadhyayUniversity of California San Francisco.ORCID https://orcid.org/0000-0002-7652-1043
Young Me YoonUniversity of Chicago, Illinois.
Sara E VazquezUniversity of California San Francisco and Chan Zuckerberg Biohub.
Tania E VelezUniversity of Chicago, Illinois, and University of Virginia, Charlottesville.
Kirk D JonesUniversity of California San Francisco.
Cathryn T LeeUniversity of Chicago, Illinois.
Christopher S LawUniversity of California San Francisco.
Paul J WoltersUniversity of California San Francisco.
Seoyeon LeeUniversity of California San Francisco.
Monica M YangUniversity of California San Francisco.ORCID https://orcid.org/0000-0002-2693-3648
Erica FarrandUniversity of California San Francisco.
Imre NothUniversity of Virginia, Charlottesville.
Mary E StrekUniversity of Chicago, Illinois.
Mark S AndersonUniversity of California San Francisco.
Joseph L DeRisiUniversity of California San Francisco and Chan Zuckerberg Biohub.
Anne I SperlingUniversity of Chicago, Illinois, and University of Virginia, Charlottesville.
Anthony K ShumUniversity of California San Francisco.ORCID https://orcid.org/0000-0001-5139-4802

Funding

INTERDISCIPLINARY TRAINING PROGRAM IN IMMUNOLOGYT32AI007090 · NIAID · UNIVERSITY OF CHICAGO · PI Peter Aidan Savage · 1985 to 2026
$11.7M
Unraveling the molecular mechanisms of impaired central tolerance in COPA syndromeR01AI168299 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Anthony Shum · 2022 to 2026
$3.3M
Defining the Role of Thymic Tolerance in the Pathogenesis of the COPA syndromeR01AI137249 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHUM, ANTHONY · 2018 to 2022
$2.4M
Impact of gut bacterial metabolites on lung function and diseaseK08HL165106 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Vaibhav Upadhyay · 2023 to 2026
$676k
American Heart AssociationNational Institute of Allergy and Infectious Diseases 5T32AI007090-44National Institute of Allergy and Infectious Diseases 5U19AI16National Institute of Allergy and Infectious Diseases R01AI137249National Institute of Allergy and Infectious Diseases R01AI68299NHLBI NIH HHS K08 HL165106NHLBI NIH HHS K08HL165106NIAID NIH HHS R01 AI168299NIAID NIH HHS T32 AI007090Nina Ireland Program for Lung Health at UCSFPulmonary Fibrosis FoundationUCSF Clinical Translational Sciences Institute
6 · The paper itself

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.

Identifiers

PMID38952015
PMCPMC11506559

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.