Evidence map›Paper›PMID 36300623›Full record

ArticleeLife2022

Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq.

Sara E Vazquez, Sabrina A Mann, Aaron Bodansky, Andrew F Kung, Zoe Quandt, Elise M N Ferré, Nils Landegren, Daniel Eriksson, Paul Bastard, Shen-Ying Zhang and 26 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
9.2field-weighted citation impact, top 1% of its field
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

35 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
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  8. Article
  9. Article
  10. Review
  11. Article
  12. Thymic inborn errors of immunity.The Journal of allergy and clinical immunology · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. B cell tolerance and autoimmunity: Lessons from repertoires.The Journal of experimental medicine · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

36 authors at 10 institutions in 6 countries.

Sara E Vazquez *Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-0601-7001
Sabrina A Mann *Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-4970-1073
Aaron Bodansky *Department of Pediatric Critical Care Medicine, University of California, San Francisco, San Francisco, United States.ORCID 0000-0001-8943-8233
Andrew F KungDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Zoe QuandtDiabetes Center, University of California, San Francisco, San Francisco, United States.
Elise M N FerréFungal Pathogenesis Unit, Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
Nils LandegrenDepartment of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0002-6163-9540
Daniel ErikssonDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID 0000-0001-5473-3312
Paul BastardSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University, New York, United States.
Shen-Ying ZhangSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University, New York, United States.
Jamin LiuDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Anthea MitchellDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Irina ProektDiabetes Center, University of California, San Francisco, San Francisco, United States.
David YuDiabetes Center, University of California, San Francisco, San Francisco, United States.
Caleigh Mandel-BrehmDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Chung-Yu WangDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Brenda MiaoDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-3393-9837
Gavin SowaSchool of Medicine, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-2089-8116
Kelsey ZornDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Alice Y ChanDepartment of Pediatrics, Division of Pediatric Allergy, Immunology, Bone and Marrow Transplantation, Division of Pediatric Rheumatology, University of California, San Francisco, San Francisco, United States.
Veronica M TagiDivision of Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States.
Chisato ShimizuKawasaki Disease Research Center, Rady Children's Hospital and Department of Pediatrics, University of California, San Diego, La Jolla, United States.
Adriana TremouletKawasaki Disease Research Center, Rady Children's Hospital and Department of Pediatrics, University of California, San Diego, La Jolla, United States.
Kara LynchDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, United States.
Michael R WilsonWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-8705-5084
Olle KämpeDepartment of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0001-6091-9914
Kerry DobbsLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.ORCID 0000-0002-3432-3137
Ottavia M DelmonteLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
Rosa BacchettaDivision of Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States.
Luigi D NotarangeloLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
Jane C BurnsKawasaki Disease Research Center, Rady Children's Hospital and Department of Pediatrics, University of California, San Diego, La Jolla, United States.
Jean-Laurent CasanovaSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University, New York, United States.
Michail S LionakisFungal Pathogenesis Unit, Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
Troy R TorgersonSeattle Children's Research Institute, Seattle, United States.ORCID 0000-0003-3489-5036
Mark S Anderson *Diabetes Center, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-3093-4758
Joseph L DeRisi *Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-4611-9205
University of California, San Francisco · USNational Institutes of Health · USUniversity of California San Diego · USInserm · FRStanford University · USUppsala University · SEHoward Hughes Medical Institute · USKarolinska University Hospital · SESan Francisco General Hospital · USSeattle Children's Hospital · US

Funding

TRANSFORMING TRANSLATIONAL SCIENCE AND EDUCATION TO BENEFIT HUMAN HEALTHUL1RR024143 · NCRR · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2006 to 2011
$49.1M
Monogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19R01AI088364 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Jean-Laurent Casanova, Shen-Ying Zhang · 2010 to 2026
$8.7M
Project 3: Epitope Selection in Type 1 DiabetesP01AI118688 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 2016 to 2020
$8.4M
BMI Bioinformatics Training GrantsT32GM067547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERNANDEZ, RYAN D. · 2003 to 2022
$6.6M
Inborn errors of immunity in patients with life-threatening COVID-19R01AI163029 · NIAID · ROCKEFELLER UNIVERSITY · PI CASANOVA, JEAN-LAURENT, ZHANG, QIAN · 2021 to 2025
$3.7M
The Role of RFX6 in Type 1 DiabetesF30DK123915 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VAZQUEZ, SARA · 2019 to 2022
$183k
NCRR NIH HHS UL1 RR024143NIAID NIH HHS P01 AI118688NIAID NIH HHS R01 AI088364NIAID NIH HHS R01 AI163029NIDDK NIH HHS F30 DK123915NIGMS NIH HHS T32 GM067547
6 · The paper itself

Abstract

Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.

Indexed as

Autoimmune DiseasesBacteriophagesCOVID-19AutoantibodiesAutoantigensAutoimmunityHomeodomain ProteinsHumansImmunoprecipitationProteomeAutoantibodiesAutoantigensHomeodomain ProteinsProteomeAPS1autoantibodyautoantigenCOVID-19humanimmunologyinflammationIPEXPhIP-seq

Identifiers

PMID36300623
PMCPMC9711525
OpenAlexW4307426052

What Socratic holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

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 Socratic graph.