Evidence map›Paper›PMID 40033084›Full record

ArticleCellular & molecular immunology2025

Systematic mining and quantification reveal the dominant contribution of non-HLA variations to acute graft-versus-host disease.

Shuang Liang, Yu-Jian Kang, Mingrui Huo, De-Chang Yang, Min Ling, Keli Yue, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Chen-Rui Xia and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular & molecular immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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

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

17 authors.

Shuang Liang *Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Yu-Jian Kang *State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Biomedical Pioneering Innovative Center (BIOPIC) & Beijing Advanced Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking University, Beijing, China.
Mingrui HuoPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
De-Chang YangState Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Biomedical Pioneering Innovative Center (BIOPIC) & Beijing Advanced Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking University, Beijing, China.
Min LingPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Keli YuePeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Yu WangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Lan-Ping XuPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.ORCID 0000-0002-0267-1081
Xiao-Hui ZhangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Chen-Rui XiaState Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Biomedical Pioneering Innovative Center (BIOPIC) & Beijing Advanced Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking University, Beijing, China.
Jing-Yi LiState Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Biomedical Pioneering Innovative Center (BIOPIC) & Beijing Advanced Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking University, Beijing, China.
Ning WuPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Ruoyang LiuPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Xinyu DongPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Jiangying LiuPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China. xys_liujiangying@pkuph.edu.cn.ORCID 0000-0002-6437-4330
Ge GaoState Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Biomedical Pioneering Innovative Center (BIOPIC) & Beijing Advanced Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking University, Beijing, China. gaog@mail.cbi.pku.edu.cn.ORCID 0000-0001-6470-8815
Xiao-Jun HuangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China. huangxiaojun@bjmu.edu.cn.ORCID 0000-0002-2145-6643

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human leukocyte antigen (HLA) disparity between donors and recipients is a key determinant triggering intense alloreactivity, leading to a lethal complication, namely, acute graft-versus-host disease (aGVHD), after allogeneic transplantation. Moreover, aGVHD remains a cause of mortality after HLA-matched allogeneic transplantation. Protocols for HLA-haploidentical hematopoietic cell transplantation (haploHCT) have been established successfully and widely applied, further highlighting the urgency of performing panoramic screening of non-HLA variations correlated with aGVHD. On the basis of our time-consecutive large haploHCT cohort (with a homogenous discovery set and an extended confirmatory set), we first delineated the genetic landscape of 1366 samples to quantitatively model aGVHD risk by assessing the contributions of HLA and non-HLA genes together with clinical factors. In addition to identifying multiple loss-of-function (LoF) risk variations in non-HLA coding genes, our data-driven study revealed that non-HLA genetic variations, independent of HLA disparity, contributed the most to the occurrence of aGVHD. This unexpected major effect was verified in an independent cohort that received HLA-identical sibling HCT. Subsequent functional experiments further revealed the roles of a representative non-HLA LoF gene and LoF gene pair in regulating the alloreactivity of primary human T cells. Our findings highlight the importance of non-HLA genetic risk in the new era of transplantation and propose a new direction to explore the immunogenetic mechanism of alloreactivity and to optimize donor selection strategies for allogeneic transplantation.

Indexed as

Data MiningGenetic VariationGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHLA AntigensAcute DiseaseAdultFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedT-LymphocytesTransplantation, HomologousHLA AntigensAcute graft-versus-host diseaseAlloreactivityGenetic riskMachine-learning modelWhole-genome sequencing

Identifiers

PMID40033084
PMCPMC12041598

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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.