Email Alerts
RSS
Volume 40 Issue 6
Jun.  2024
Turn off MathJax
Article Contents
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2024  >  40(6): 572-578
Wu HL,Chen YF,Li ST,et al.Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method[J].Chin J Burns Wounds,2024,40(6):572-578.DOI: 10.3760/cma.j.cn501225-20240203-00046.
Citation: Wu HL,Chen YF,Li ST,et al.Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method[J].Chin J Burns Wounds,2024,40(6):572-578.DOI: 10.3760/cma.j.cn501225-20240203-00046.
shu

Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method

doi: 10.3760/cma.j.cn501225-20240203-00046
  • 1.

    Department of Burn and Wound Repair Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

  • 2.

    Department of Plastic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

Funds:

General Program of National Natural Science Foundation of China 82172213

More Information
    Abstract
  •   Objective  To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.  Methods  This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells.  Results  The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS (PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS (P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS (P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS (P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells (P>0.05).  Conclusions  From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

     

    • FullText(HTML)
  • loading
    • References(29)
  • [1]
    CaiH, LiuX, LiuD, et al. GEO data mining identifies potential immune-related genes in hypertrophic scar and verities in a rabbit model[J]. Heliyon, 2023,9(7):e17266. DOI: 10.1016/j.heliyon.2023.e17266.
    [2]
    LimandjajaGC, NiessenFB, ScheperRJ, et al. Hypertrophic scars and keloids: overview of the evidence and practical guide for differentiating between these abnormal scars[J]. Exp Dermatol, 2021,30(1):146-161. DOI: 10.1111/exd.14121.
    [3]
    Ud-DinS, BayatA. Controlling inflammation pre-emptively or at the time of cutaneous injury optimises outcome of skin scarring[J]. Front Immunol, 2022,13:883239. DOI: 10.3389/fimmu.2022.883239.
    [4]
    ShakerSA, AyuobNN, HajrahNH. Cell talk: a phenomenon observed in the keloid scar by immunohistochemical study[J]. Appl Immunohistochem Mol Morphol, 2011,19(2):153-159. DOI: 10.1097/PAI.0b013e3181efa2ef.
    [5]
    GauglitzGG, KortingHC, PavicicT, et al. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies[J]. Mol Med, 2011,17(1/2):113-125. DOI: 10.2119/molmed.2009.00153.
    [6]
    WangZC, ZhaoWY, CaoY, et al. The roles of inflammation in keloid and hypertrophic scars[J]. Front Immunol, 2020,11:603187. DOI: 10.3389/fimmu.2020.603187.
    [7]
    WongVW, PaternoJ, SorkinM, et al. Mechanical force prolongs acute inflammation via T-cell-dependent pathways during scar formation[J]. FASEB J, 2011,25(12):4498-4510. DOI: 10.1096/fj.10-178087.
    [8]
    ChenB, LiH, XiaW. Imiquimod regulating Th1 and Th2 cell-related chemokines to inhibit scar hyperplasia[J]. Int Wound J, 2019,16(6):1281-1288. DOI: 10.1111/iwj.13183.
    [9]
    CarterAR, SandersonE, HammertonG, et al. Mendelian randomisation for mediation analysis: current methods and challenges for implementation[J]. Eur J Epidemiol, 2021,36(5):465-478. DOI: 10.1007/s10654-021-00757-1.
    [10]
    杨亮亮, 邓辰亮, 杨松林. 巨噬细胞在增生性瘢痕形成机制中的研究进展[J].中国美容整形外科杂志,2019,30(3):191-192,后插1. DOI: 10.3969/j.issn.1673-7040.2019.03.021.
    [11]
    BoothbyIC, CohenJN, RosenblumMD. Regulatory T cells in skin injury: at the crossroads of tolerance and tissue repair[J]. Sci Immunol, 2020,5(47):eaaz9631.DOI: 10.1126/sciimmunol.aaz9631.
    [12]
    BirneyE. Mendelian randomization[J]. Cold Spring Harb Perspect Med, 2022,12(4):a041302.DOI: 10.1101/cshperspect.a041302.
    [13]
    OrrùV, SteriM, SidoreC, et al. Complex genetic signatures in immune cells underlie autoimmunity and inform therapy[J]. Nat Genet, 2020,52(10):1036-1045. DOI: 10.1038/s41588-020-0684-4.
    [14]
    SidoreC, BusoneroF, MaschioA, et al. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers[J]. Nat Genet, 2015,47(11):1272-1281. DOI: 10.1038/ng.3368.
    [15]
    GuJ, YanGM, KongXL, et al. Assessing the causal relationship between immune traits and systemic lupus erythematosus by bi-directional Mendelian randomization analysis[J]. Mol Genet Genomics, 2023,298(6):1493-1503. DOI: 10.1007/s00438-023-02071-9.
    [16]
    1000 Genomes Project Consortium, AutonA, BrooksLD, et al. A global reference for human genetic variation[J]. Nature, 2015,526(7571):68-74. DOI: 10.1038/nature15393.
    [17]
    ShortWD, OlutoyeOO, PadonBW, et al. Advances in non-invasive biosensing measures to monitor wound healing progression[J]. Front Bioeng Biotechnol, 2022,10:952198. DOI: 10.3389/fbioe.2022.952198.
    [18]
    LiuY, Chinese Burn Association. Chinese expert consensus on the management of pediatric deep partial-thickness burn wounds (2023 edition)[J/OL]. Burns Trauma, 2023,11:tkad053[2024-02-03]. https://pubmed.ncbi.nlm.nih.gov/37936895/. DOI: 10.1093/burnst/tkad053.
    [19]
    AlBarashdi MA, AliA, McMullinMF, et al. Protein tyrosine phosphatase receptor type C (PTPRC or CD45)[J]. J Clin Pathol,2021,74(9):548-552. DOI: 10.1136/jclinpath-2020-206927.
    [20]
    HollandDB, JeremyAH, RobertsSG, et al. Inflammation in acne scarring: a comparison of the responses in lesions from patients prone and not prone to scar[J]. Br J Dermatol, 2004,150(1):72-81. DOI: 10.1111/j.1365-2133.2004.05749.x.
    [21]
    ChenZ, ZhouL, WonT, et al. Characterization of CD45RO+ memory T lymphocytes in keloid disease[J]. Br J Dermatol, 2018,178(4):940-950. DOI: 10.1111/bjd.16173.
    [22]
    RoweM, HildrethJE, RickinsonAB, et al. Monoclonal antibodies to Epstein-Barr virus-induced, transformation-associated cell surface antigens: binding patterns and effect upon virus-specific T-cell cytotoxicity[J]. Int J Cancer, 1982,29(4):373-381. DOI: 10.1002/ijc.2910290403.
    [23]
    樊华, 贺强. CD39与调节性T细胞的研究进展[J/CD].中华临床医师杂志(电子版),2013,7(17):125-126. DOI: 10.3877/cma.j.issn.1674-0785.2013.17.057.
    [24]
    FerrariD, GambariR, IdzkoM, et al. Purinergic signaling in scarring[J]. FASEB J, 2016,30(1):3-12. DOI: 10.1096/fj.15-274563.
    [25]
    EltzschigHK, SitkovskyMV, RobsonSC. Purinergic signaling during inflammation[J]. N Engl J Med, 2012,367(24):2322-2333. DOI: 10.1056/NEJMra1205750.
    [26]
    FernándezP, Perez-AsoM, SmithG, et al. Extracellular generation of adenosine by the ectonucleotidases CD39 and CD73 promotes dermal fibrosis[J]. Am J Pathol, 2013,183(6):1740-1746. DOI: 10.1016/j.ajpath.2013.08.024.
    [27]
    HuangX, GuS, LiuC, et al. CD39+ fibroblasts enhance myofibroblast activation by promoting IL-11 secretion in hypertrophic scars[J]. J Invest Dermatol, 2022,142(4):1065-1076.e19. DOI: 10.1016/j.jid.2021.07.181.
    [28]
    ChenY, JinQ, FuX, et al. Connection between T regulatory cell enrichment and collagen deposition in keloid[J]. Exp Cell Res, 2019,383(2):111549. DOI: 10.1016/j.yexcr.2019.111549.
    [29]
    KnoedlerS, KnoedlerL, Kauke-NavarroM, et al. Regulatory T cells in skin regeneration and wound healing[J]. Mil Med Res, 2023,10(1):49. DOI: 10.1186/s40779-023-00484-6.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(5)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (266) PDF downloads(23) Cited by()
    Proportional views
    Related

    Copyright © Chinese Journal of Burns京ICP备07035254号-14

    E-mail：shaoshangzazhi@163.com

    Website：https://zhsszz.xml-journal.net/

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return