Evidence map›Paper›PMID 41774077›Full record

ArticleThe Journal of experimental medicine2026

Immune profiling links autoimmune hepatitis to human herpesvirus 6 and relaxin receptor antigens.

Arielle Klepper, James Asaki, Colette M Caspar, Andrew F Kung, Sara E Vazquez, Aaron Bodansky, Anthea Mitchell, Sabrina A Mann, Kelsey Zorn, Isaac Avila-Vargas and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Experimental Models of Autoimmune Hepatitis: Disease Fidelity and Translational Relevance.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Review
  2. Review
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

28 authors.

Arielle KlepperDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-5227-5044
James AsakiDepartment of Biochemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-8201-6588
Colette M CasparDepartment of Biochemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0009-0008-6803-1600
Andrew F KungDepartment of Biochemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0009-0002-8039-5972
Sara E VazquezDepartment of Dermatology, Mass General Hospital, Boston, MA, USA.ORCID 0000-0002-0601-7001
Aaron BodanskyDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-8943-8233
Anthea MitchellChan Zuckerberg Biohub , San Francisco, CA, USA.ORCID 0000-0002-2885-6199
Sabrina A MannDepartment of Biochemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-4970-1073
Kelsey ZornDepartment of Biochemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-1227-2137
Isaac Avila-VargasDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0009-0002-8034-3347
Swathi KariDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Melawit TekesteDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Javier CastroDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-7784-0003
Briton LeeDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-7314-613X
Maria DuarteDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5906-7507
Mandana KhaliliDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9178-9139
Monica YangDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2693-3648
Paul WoltersDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-3108-6164
Jennifer PriceDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-3825-5696
Emily PeritoDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2911-9684
Sandy FengDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2601-4350
Jacquelyn J MaherDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2509-8484
Michael R WilsonORCID 0000-0002-8705-5084
Jennifer C LaiDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-2092-6380
Christina Weiler-NormannDepartment of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ansgar W LohseDepartment of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0002-8823-3129
Joseph DeRisi *Department of Biochemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-4611-9205
Michele May-Sien TanaDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-3665-2735

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
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
Molecular characterization of ascites fluid to identify drivers of infection in patients with decompensated cirrhosisK08DK139453 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Arielle Klepper · 2025 to 2026
$347k
American Association for the Study of Liver DiseasesChan Zuckerberg Biohub San FranciscoNIAAA NIH HHS K24 AA022523NIA NIH HHS K24 AG080021NIA NIH HHS R01 AG059183NIA NIH HHS R21 AG067554NIDDK NIH HHS K08 DK139453NIDDK NIH HHS P30 DK026743NIDDK NIH HHS R21 DK127275NIDDK NIH HHS T32 DK060414NIH HHS 1R21DK127275-01NIH HHS K08DK139453NIH HHS K24AA022523NIH HHS K24AG080021NIH HHS P30DK026743NIH HHS R01AG059183NIH HHS R21AG067554NIH HHS T32DK060414Nina Ireland Program for Lung HealthUniversity of California, San FranciscoUniversity of California, San Francisco, Department of Medicine
6 · The paper itself

Abstract

Autoimmune hepatitis (AIH) is a severe, chronic disease where IgG elevation and autoantibody profile are defining features. However, linking autoantibodies to AIH pathogenesis remains elusive. We employed phage-display immunoprecipitation sequencing and uncovered a novel humoral signature specific to AIH. Embedded within this signature were antibodies against the known AIH autoantigen SLA/LP and novel reactivities to disco-interacting protein 2 homolog A (DIP2A), and the relaxin family peptide receptor 1 (RXFP1). Fine mapping of the DIP2A epitope revealed preferential enrichment for a nearly identical 9-amino acid sequence derived from the U27 protein of human herpesvirus 6 (HHV6). Preincubation with the HHV6 epitope blocked DIP2A binding, consistent with cross-reactivity. AIH patients positive for anti-DIP2A had higher titers of HHV6 IgG, suggestive of reactivation. AIH patients had antibodies against the antifibrotic receptor, RXFP1, which inhibited relaxin-2 signaling in an IgG-dependent manner. These data provide evidence for a novel serological profile in AIH, linking HHV6 reactivation anti-RXFP1 antibodies to disease pathogenesis.

Indexed as

Hepatitis, AutoimmuneHerpesvirus 6, HumanReceptors, G-Protein-CoupledReceptors, PeptideAutoantibodiesAutoantigensFemaleHumansImmunoglobulin GAutoantibodiesAutoantigensImmunoglobulin GReceptors, G-Protein-CoupledReceptors, PeptideRXFP1 protein, human

Identifiers

PMID41774077
PMCPMC12955711

What Socratic holds

Textmetadata
LicenceCC BY
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.