Evidence map›Paper›PMID 18773898›Full record

ArticleGastroenterology2008

Identification of CD4 T-cell epitopes in soluble liver antigen/liver pancreas autoantigen in autoimmune hepatitis.

Heiko Mix, Christina Weiler-Normann, Robert Thimme, Golo Ahlenstiel, Eui-Cheol Shin, Johannes Herkel, Chella S David, Ansgar W Lohse, Barbara Rehermann

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

17 citing papers in PubMed, 49 citations in OpenAlex.

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  14. Advances in the current treatment of autoimmune hepatitis.Digestive diseases and sciences · 2012
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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

9 authors at 6 institutions in 2 countries.

Heiko MixImmunology Section, Liver Diseases Branch, National Institute for Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-1800, USA.
Christina Weiler-Normann
Robert Thimme
Golo Ahlenstiel
Eui-Cheol Shin
Johannes Herkel
Chella S David
Ansgar W Lohse
Barbara Rehermann
National Institutes of Health · USNational Institute of Diabetes and Digestive and Kidney Diseases · USJohannes Gutenberg University Mainz · DEMayo Clinic · USUniversity Medical Center Freiburg · DEUniversity Medical Center Hamburg-Eppendorf · DE

Funding

Immune responses in autoimmune liver diseasesZIADK054515 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI REHERMANN, BARBARA · 2009 to 2013
$836k
Immune responses in autoimmune liver diseasesZ01DK054515 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI REHERMANN, BARBARA · 2007 to 2008
$583k
Intramural NIH HHS Z01 DK054515
6 · The paper itself

Abstract

BACKGROUND &

aimsAutoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with autoantibodies and liver-infiltrating lymphocytes. Although autoantibodies are tested routinely to diagnose and classify AIH, liver-infiltrating lymphocytes are regarded as the primary factor for disease pathogenesis. The purpose of this study was to identify and characterize autoantigenic peptides within human AIH-specific soluble liver antigen/liver pancreas antigen (SLA/LP) that are targeted by CD4(+) T cells and restricted by the disease susceptibility gene HLA-DRB1*0301.

methodsHLA-DRB1*0301 transgenic mice were immunized with SLA/LP. Antibody and T-cell responses were analyzed with SLA/LP-overlapping peptides in enzyme immunoassay, proliferation, and enzyme-linked immunospot (ELISpot) assays. Minimal optimal T-cell epitopes were identified, characterized with cloned T-cell hybridomas, and confirmed in tetramer and ELISpot assays with AIH patients' peripheral blood mononuclear cells.

resultsAll mice developed SLA/LP-specific IgG1/IgG2a antibodies against the same SLA/LP peptides as human beings. T cells targeted several peptides within SLA/LP, 2 of which were DR3-restricted and one overlapped the sequence recognized by human autoantibodies. Minimal optimal epitopes were mapped, DRB1*0301/epitope-tetramers were generated, and the frequency and function of HLA-DRB1*0301-restricted autoantigen-specific T cells in AIH patients were analyzed with tetramer and interferon-gamma ELISpot assays.

conclusionsThis study identified T-cell epitopes within SLA/LP, restricted by the disease susceptibility gene DRB1*0301 and in close proximity to the human autoantibody epitope. These results and the generated reagents now provide the opportunity to directly monitor autoreactive T cells in AIH patients in clinical studies.

Indexed as

AdultAgedAnimalsAutoantibodiesAutoantigensCD4-Positive T-LymphocytesDisease Models, AnimalEpitopes, T-LymphocyteFemaleHepatitis, AutoimmuneHumansImmunoenzyme TechniquesMaleMiceMice, Inbred C57BLMice, TransgenicAutoantibodiesAutoantigensEpitopes, T-Lymphocyteliver antigen LA-1

Identifiers

PMID18773898
PMCPMC2708941
OpenAlexW2008811593

What OpenQuestion holds

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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 OpenQuestion graph.