Evidence map›Paper›PMID 40835749›Full record

ArticleDiabetologia2025

Profiling associations of interactive ligand-receptors (HLA class I and KIR gene products) with the progression to type 1 diabetes among seroconverted participants.

Lue Ping Zhao, George K Papadopoulos, Benjamin J McFarland, Jay S Skyler, Hemang M Parikh, William W Kwok, Terry P Lybrand, George P Bondinas, Antonis K Moustakas, Ruihan Wang and 4 more

Erratum issuedAbstract read
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In one paragraph

Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Lue Ping ZhaoPublic Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, WA, USA. lzhao@fredhutch.org.ORCID http://orcid.org/0000-0002-1387-7165
George K PapadopoulosLaboratory of Biophysics, Biochemistry, Biomaterials and Bioprocessing, Faculty of Agricultural Technology, Technological Educational Institute (TEI) of Epirus, Arta, Greece.ORCID http://orcid.org/0000-0002-6944-6591
Benjamin J McFarlandDepartment of Biochemistry, Seattle Pacific University, Seattle, USA.ORCID http://orcid.org/0000-0001-9785-6670
Jay S SkylerDiabetes Research Institute and Division of Endocrinology, Diabetes & Metabolism, University of Miami Miler School of Medicine, Miami, Florida, USA.ORCID http://orcid.org/0000-0003-1136-8110
Hemang M ParikhHealth Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.ORCID http://orcid.org/0000-0002-9076-6709
William W KwokBenaroya Research Institute, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-4843-4599
Terry P LybrandDepartment of Chemistry, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-2248-104X
George P BondinasDepartment of Food Science and Technology, Faculty of Environmental Sciences, Ionian University, Argostoli, Cephalonia, Greece.
Antonis K MoustakasDepartment of Food Science and Technology, Faculty of Environmental Sciences, Ionian University, Argostoli, Cephalonia, Greece.ORCID http://orcid.org/0009-0003-9705-9526
Ruihan WangClinical Research Division, Fred Hutchinson Cancer Research Centre, Seattle, WA, USA.
Chul-Woo PyoClinical Research Division, Fred Hutchinson Cancer Research Centre, Seattle, WA, USA.
Wyatt C NelsonClinical Research Division, Fred Hutchinson Cancer Research Centre, Seattle, WA, USA.
Daniel E GeraghtyClinical Research Division, Fred Hutchinson Cancer Research Centre, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-7702-5650
Åke LernmarkDepartment of Clinical Sciences, Lund University CRC, Skåne University Hospital, Malmö, Sweden. ake.lernmark@med.lu.se.ORCID http://orcid.org/0000-0003-1735-0499

Funding

Characterizing Immunogenetics in Type 1 DiabetesR01DK132406 · NIDDK · FRED HUTCHINSON CANCER CENTER · PI GERAGHTY, DANIEL E., LERNMARK, AKE · 2023 to 2025
$1.7M
NIDDK NIH HHS R01 DK132406
6 · The paper itself

Abstract

aims/hypothesisThe aim of this work was to explore associations between type 1 diabetes progression from stages 1 or 2 to stage 3 and interacting ligand-receptor complexes of HLA class I (HLA-I) and KIR gene products.

methodsApplying next-generation sequencing technology to genotype HLA-I genes (HLA-A, -B, -C) and KIR genes (KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL3, KIR3DS1, KIR2DP1, KIR3DP1) from 1215 participants in the Diabetes Prevention Trial-Type 1 (DPT-1) and the Diabetes Prevention Trial (TN07), we systematically explored associations of HLA-I-KIR ligand-receptor interactions (LRIs) with disease progression via a Cox regression model. We investigated the structural properties of identified LRI complexes.

resultsKIR and HLA-I genes had no or sporadic associations with disease progression. Out of all possible LRIs, nine HLA-A Ligands and 14 HLA-B ligands with corresponding receptors had modest associations with progression (p<0.05). As an example, carriers of A*03:01-KIR2DS4 had slower progression (HR 0.36, p=3.06 × 10 CONCLUSIONS/

interpretationThese results reveal that LRIs of KIR-HLA-I gene products, rather than individual genes, contribute to type 1 diabetes progression, and such interactions are likely to be stabilised by electrostatic and van der Waals forces. As the KIR-HLA-I interactions involve part of the C-terminus of the antigen-binding groove of HLA-I, but may be affected by the respective bound peptide, this suggests a new mechanism for type 1 diabetes pathogenesis. DATA AVAILABILITY: Clinical data on participants in DPT-1 and TN07 can be obtained from the NIDDK-Central Repository ( https://repository.niddk.nih.gov/home ) following the formal approval process.

Indexed as

Diabetes Mellitus, Type 1Histocompatibility Antigens Class IReceptors, KIRAdultDisease ProgressionFemaleGenotypeHumansLigandsMaleHistocompatibility Antigens Class ILigandsReceptors, KIRHLAImmunogeneticsIslet autoimmunityKiller-cell immunoglobulin-like receptorsKIRNatural killer (NK) cellsProgressionSeroconversionType 1 diabetes

Identifiers

PMID40835749
PMCPMC12594725

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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 OpenQuestion graph.