Evidence map›Paper›PMID 25243383›Full record

Trial reportLiver international : official journal of the International Association for the Study of the Liver2015

Anti-kelch-like 12 and anti-hexokinase 1: novel autoantibodies in primary biliary cirrhosis.

Gary L Norman, Chen-Yen Yang, Heather P Ostendorff, Zakera Shums, Mark J Lim, Jinjun Wang, Amany Awad, Gideon M Hirschfield, Piotr Milkiewicz, Donald B Bloch and 8 more

Open access · greenAbstract readClinical Trial
In one paragraph

Trial report in Liver international : official journal of the International Association for the Study of the Liver, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Guideline
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  11. Article
  12. Review
  13. Risk Stratification in Primary Biliary Cholangitis.Journal of clinical medicine · 2023
    Review
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  15. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 10 institutions in 5 countries.

Gary L NormanInova Diagnostics, San Diego, CA, USA.
Chen-Yen Yang
Heather P Ostendorff
Zakera Shums
Mark J Lim
Jinjun Wang
Amany Awad
Gideon M Hirschfield
Piotr Milkiewicz
Donald B Bloch
Kenneth J Rothschild
Christopher L Bowlus
Iannis E Adamopoulos
Patrick S C Leung
Harry J Janssen
Angela C Cheung
Catalina Coltescu
M Eric Gershwin
University of California, Davis · USAmbergen (United States) · USNova Medical (United States) · USErasmus MC · NLMassachusetts General Hospital · USMedical University of Warsaw · PLShriners Hospitals for Children - Northern California · USUniversity Health Network · CAUniversity of Birmingham · GBUniversity of Toronto · CA

Funding

The IL-23/IL-17 Axis in Inflammatory ArthritisR01AR062173 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEVY, DAN · 2012 to 2025
$4.9M
MECHANISMS AND PATHOGENESIS OF PRIMARY BILIARY CIRRHOSISR37DK039588 · NIDDK · UNIVERSITY OF CALIFORNIA DAVIS · PI GERSHWIN, MERRILL E · 2001 to 2010
$3.5M
Novel Proteomic Arrays of In Vitro Expressed Proteins for Autoimmune DiseaseR44AI052525 · NIAID · AMBERGEN, INC · PI LIM, MARK · 2007 to 2009
$2.1M
MECHANISMS AND PATHOGENESIS OF PRIMARY BILIARY CIRRHOSISR01DK039588 · NIDDK · UNIVERSITY OF CALIFORNIA DAVIS · PI GERSHWIN, MERRILL E · 1988 to 2015
$2.0M
NIAID NIH HHS R44 AI052525NIAMS NIH HHS R01 AR062173NIDDK NIH HHS R01 DK039588NIDDK NIH HHS R37 DK039588
6 · The paper itself

Abstract

BACKGROUND &

aimsUsing high-density human recombinant protein microarrays, we identified two potential biomarkers, kelch-like 12 (KLHL12) and hexokinase-1 (HK1), in primary biliary cirrhosis (PBC). The objective of this study was to determine the diagnostic value of anti-KLHL12/HK1 autoantibodies in PBC. Initial discovery used sera from 22 patients with PBC and 62 non-PBC controls. KLHL12 and HK1 proteins were then analysed for immunoglobulin reactivity by immunoblot and enzyme-linked immunosorbent assay (ELISA) in two independent cohorts of PBC and disease/healthy control patients.

methodsSerum samples from 100 patients with PBC and 165 non-PBC disease controls were analysed by immunoblot and samples from 366 patients with PBC, 174 disease controls, and 80 healthy donors were tested by ELISA.

resultsAnti-KLHL12 and anti-HK1 antibodies were each detected more frequently in PBC compared with non-PBC disease controls (P < 0.001). Not only are both markers highly specific for PBC (≥95%) but they also yielded higher sensitivity than anti-gp210 and anti-sp100 antibodies. Combining anti-HK1 and anti-KLHL12 with available markers (MIT3, gp210 and sp100), increased the diagnostic sensitivity for PBC. Most importantly, anti-KLHL12 and anti-HK1 antibodies were present in 10-35% of anti-mitochondrial antibody (AMA)-negative PBC patients and adding these two biomarkers to conventional PBC assays dramatically improved the serological sensitivity in AMA-negative PBC from 55% to 75% in immunoblot and 48.3% to 68.5% in ELISA.

conclusionsThe addition of tests for highly specific anti-KLHL12 and anti-HK1 antibodies to AMA and ANA serological assays significantly improves efficacy in the clinical detection and diagnosis of PBC, especially for AMA-negative subjects.

Indexed as

AutoantibodiesAdaptor Proteins, Signal TransducingBiomarkersEnzyme-Linked Immunosorbent AssayHexokinaseHumansImmunoblottingLiver Cirrhosis, BiliaryMicrofilament ProteinsProtein Array AnalysisSensitivity and SpecificityAdaptor Proteins, Signal Transducinganti-hexokinase 1 antibody, humananti-KLHL12 antibody, humanAutoantibodiesBiomarkersHexokinaseHK1 protein, humanKLHL12 protein, humanMicrofilament Proteinsdiagnosticsliverserology

Identifiers

PMID25243383
PMCPMC4305042
OpenAlexW2044395170

What OpenQuestion holds

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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 OpenQuestion graph.