Evidence map›Paper›PMID 37398174›Full record

ArticlemedRxiv : the preprint server for health sciences2024

Novel autoantibody targets identified in patients with autoimmune hepatitis (AIH) by PhIP-Seq reveals pathogenic insights.

Arielle Klepper, James Asaki, Andrew F Kung, Sara E Vazquez, Aaron Bodansky, Anthea Mitchell, Sabrina A Mann, Kelsey Zorn, Isaac Avila-Vargas, Swathi Kari and 16 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 6 citations in OpenAlex.

No citing paper in PubMed yet.

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

26 authors at 3 institutions in 2 countries.

Arielle KlepperDepartment of Medicine, University of California, San Francisco, USA.ORCID 0000-0002-5227-5044
James AsakiDepartment of Biochemistry, University of California, San Francisco, USA.
Andrew F KungDepartment of Biochemistry, University of California, San Francisco, USA.ORCID 0009-0002-8039-5972
Sara E VazquezDepartment of Dermatology, Mass General Hospital, Boston, MA.
Aaron BodanskyDepartment of Pediatrics, University of California, San Francisco, USA.
Anthea MitchellChan Zuckerberg Biohub; San Francisco, CA, USA.
Sabrina A MannDepartment of Biochemistry, University of California, San Francisco, USA.
Kelsey ZornDepartment of Biochemistry, University of California, San Francisco, USA.
Isaac Avila-VargasDepartment of Medicine, University of California, San Francisco, USA.
Swathi KariDepartment of Medicine, University of California, San Francisco, USA.
Melawit TekesteDepartment of Medicine, University of California, San Francisco, USA.
Javier CastroDepartment of Medicine, University of California, San Francisco, USA.
Briton LeeDepartment of Medicine, University of California, San Francisco, USA.
Maria DuarteDepartment of Medicine, University of California, San Francisco, USA.
Mandana KhaliliDepartment of Medicine, University of California, San Francisco, USA.
Monica YangDepartment of Medicine, University of California, San Francisco, USA.
Paul WoltersDepartment of Medicine, University of California, San Francisco, USA.
Jennifer PriceDepartment of Medicine, University of California, San Francisco, USA.
Emily PeritoDepartment of Pediatrics, University of California, San Francisco, USA.
Sandy FengDepartment of Surgery, University of California, San Francisco, USA.
Jacquelyn J MaherDepartment of Medicine, University of California, San Francisco, USA.
Jennifer C LaiDepartment of Medicine, University of California, San Francisco, USA.
Christina Weiler-NormannDepartment of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ansgar W LohseDepartment of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Joseph DeRisiDepartment of Biochemistry, University of California, San Francisco, USA.ORCID 0000-0002-4611-9205
Michele TanaDepartment of Medicine, University of California, San Francisco, USA.
University of California, San Francisco · USUniversität Hamburg · DEGladstone Institutes · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
The spectrum of cognitive impairment including Alzheimer’s Disease and Related Dementias after liver transplantationR01AG059183 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer C. Lai · 2018 to 2026
$9.9M
NRSA Hepatology Training GrantT32DK060414 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mandana Khalili, JACQUELYN J. MAHER · 2002 to 2026
$6.8M
BMI Bioinformatics Training GrantsT32GM067547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERNANDEZ, RYAN D. · 2003 to 2022
$6.6M
Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher, Anita Sil · 2020 to 2026
$4.5M
Mentoring Multidisciplinary Patient-Oriented Research in Viral HepatitisK24AA022523 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KHALILI, MANDANA · 2013 to 2023
$1.9M
The Impact of Frailty on Liver Transplant Outcomes in Older Adults with Hepatocellular CarcinomaK24AG080021 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer C. Lai · 2023 to 2026
$755k
A Multiomic Search for Antigens in Autoimmune HepatitisR21DK127275 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TANA, MICHELE MAY-SIEN · 2020 to 2021
$444k
Development of a laboratory frailty index to improve prediction of mortality in patients with cirrhosis awaiting liver transplantationR21AG067554 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAI, JENNIFER C. · 2020 to 2021
$444k
NIAAA NIH HHS K24 AA022523NIA NIH HHS K24 AG080021NIA NIH HHS R01 AG059183NIA NIH HHS R21 AG067554NIDDK NIH HHS P30 DK026743NIDDK NIH HHS R21 DK127275NIDDK NIH HHS T32 DK060414NIGMS NIH HHS T32 GM067547NIGMS NIH HHS T32 GM136547
6 · The paper itself

Abstract

Background and Aims: Autoimmune hepatitis (AIH) is a severe disease characterized by elevated immunoglobin levels. However, the role of autoantibodies in the pathophysiology of AIH remains uncertain. Methods: Phage Immunoprecipitation-Sequencing (PhIP-seq) was employed to identify autoantibodies in the serum of patients with AIH ( Results: Logistic regression using PhIP-seq enriched peptides as inputs yielded a classification AUC of 0.81, indicating the presence of a predictive humoral immune signature for AIH. Embedded within this signature were disease relevant targets, including SLA/LP, the target of a well-recognized autoantibody in AIH, disco interacting protein 2 homolog A (DIP2A), and the relaxin family peptide receptor 1 (RXFP1). The autoreactive fragment of DIP2A was a 9-amino acid stretch nearly identical to the U27 protein of human herpes virus 6 (HHV-6). Fine mapping of this epitope suggests the HHV-6 U27 sequence is preferentially enriched relative to the corresponding DIP2A sequence. Antibodies against RXFP1, a receptor involved in anti-fibrotic signaling, were also highly specific to AIH. The enriched peptides are within a motif adjacent to the receptor binding domain, required for signaling and serum from AIH patients positive for anti-RFXP1 antibody was able to significantly inhibit relaxin-2 singling. Depletion of IgG from anti-RXFP1 positive serum abrogated this effect. Conclusions: These data provide evidence for a novel serological profile in AIH, including a possible functional role for anti-RXFP1, and antibodies that cross react with HHV6 U27 protein.

Identifiers

PMID37398174
PMCPMC10312872
OpenAlexW4380450207

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.