Abstract
Objectives: Graft-versus-host disease (GVHD) is the most common complication after hematopoietic stem cell transplantation (HSCT) and remains to be a major cause of mortality. Activation of toll-like receptor 4 (TLR-4) by lipopolysaccharide induces the NF-κB signaling pathway to release critical proinflammatory cytokines and increases the recipient response to GVHD. In order to clarify the role of TLR-4 in the occurrence of acute GVHD after HSCT, we collected 208 samples from HSCT recipients and their human lecucyte antigen identical donors to test the hypothesis that TLR-4polymorphism in the recipients or donors influence the risk of acute GVHD in allogeneic HSCT recipients.
Methods: TLR-4 Asp299Gly and Thr399Ile polymorphisms of each sample were examined by using DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods.
Results: No homozygous or heterozygous variant alleles of the Asp299Gly or Thr339Ile polymorphism were detected in any samples in our study. Our results demonstrate that TLR-4 Asp299Gly and Thr399Ile polymorphisms might be very rare in the Chinese population (Eastern China and Taiwan region).
Conclusion: The results of this study cannot confirm the role of TLR-4 mutations in the pathogenesis of GVHD in humans, yet we reach a definite conclusion by a TLR-4 knockout murine GVHD model in our ongoing project.
Keywords: Toll-like receptor 4, polymorphisms, graft-versus-host disease, mutation, chinese population, pathogenesis.
Graphical Abstract
[http://dx.doi.org/10.1111/bjh.13959] [PMID: 27019012]
[http://dx.doi.org/10.1111/sji.12597] [PMID: 28853768]
[http://dx.doi.org/10.1038/s41467-020-15161-8] [PMID: 32152304]
[http://dx.doi.org/10.2174/156652409787847137] [PMID: 19355917]
[http://dx.doi.org/10.1155/2017/8391230] [PMID: 28553556]
[http://dx.doi.org/10.1016/j.intimp.2018.06.044] [PMID: 30089605]
[http://dx.doi.org/10.1007/s10753-016-0447-7] [PMID: 27718095]
[http://dx.doi.org/10.3892/mmr.2014.2191] [PMID: 24789089]
[http://dx.doi.org/10.1038/76048] [PMID: 10835634]
[http://dx.doi.org/10.2119/2007-00135.Ferwerda] [PMID: 18231573]
[http://dx.doi.org/10.1053/bbmt.2001.v7.pm11529488] [PMID: 11529488]
[http://dx.doi.org/10.1038/cmi.2012.58] [PMID: 23262974]
[http://dx.doi.org/10.4049/jimmunol.181.9.6132] [PMID: 18941203]
[http://dx.doi.org/10.1016/j.bbmt.2009.04.012] [PMID: 19660727]
[http://dx.doi.org/10.12659/AOT.895389] [PMID: 26827181]
[http://dx.doi.org/10.1182/bloodadvances.2017011502] [PMID: 30030270]
[http://dx.doi.org/10.1182/blood-2011-09-371153] [PMID: 22282500]
[PMID: 7581076]
[http://dx.doi.org/10.1371/journal.pone.0093550] [PMID: 24695807]
[http://dx.doi.org/10.1164/rccm.200207-634OC] [PMID: 12406828]
[http://dx.doi.org/10.1016/j.mcp.2007.03.005] [PMID: 17482427]
[http://dx.doi.org/10.1111/j.1600-051X.2007.01092.x] [PMID: 17555409]
[http://dx.doi.org/10.1016/j.mad.2007.04.001] [PMID: 17493663]
[http://dx.doi.org/10.4049/jimmunol.179.5.3171] [PMID: 17709532]
[http://dx.doi.org/10.1016/j.jinf.2005.10.018] [PMID: 16343635]
[http://dx.doi.org/10.3349/ymj.2008.49.1.58] [PMID: 18306470]
[http://dx.doi.org/10.7754/Clin.Lab.2015.150145] [PMID: 26642699]
[http://dx.doi.org/10.3109/00207451003778736] [PMID: 20504212]
[http://dx.doi.org/10.7883/yoken.JJID.2014.420] [PMID: 25766605]
[http://dx.doi.org/10.1016/j.jdermsci.2016.04.014] [PMID: 27155792]
[http://dx.doi.org/10.1186/s12879-018-2943-x] [PMID: 29320990]