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. 2019 Jun;7(6):e689.
doi: 10.1002/mgg3.689. Epub 2019 May 1.

A risk assessment model of acute liver allograft rejection by genetic polymorphism of CD276

Xiaobo Yu  1   2   3   4   5 , Bajin Wei  2   3   4 , Rong Su  2   3   4 , Jia Yao  2   3   4 , Xiaowen Feng  1   2   3   4   5 , Guoping Jiang  1   2   3   4   5 , Haiyang Xie  1   2   3   4   5 , Jian Wu  1   2   3   4   5 , Xiao Xu  1   2   3   4   5 , Min Zhang  1   2   3   4   5 , Shusen Zheng  1   2   3   4   5 , Lin Zhou  1   2   3   4   5
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A risk assessment model of acute liver allograft rejection by genetic polymorphism of CD276

Xiaobo Yu et al. Mol Genet Genomic Med. 2019 Jun.

Abstract

Background: Liver transplantation is an effective therapy for end-stage liver diseases and acute liver failure. After the operation, however, recipients may suffer grafts loss induced by alloimmune reaction, which is termed as acute allograft rejection. The interaction between costimulatory molecules, CD276, and its ligand, TREML2, promotes T cell-mediated immune response, as well as acute or chronic allograft rejection. Our research aimed at correlating genetic polymorphisms of CD276/TREML2 with acute rejection, and evaluating its prognostic value of acute rejection after liver transplantation.

Methods: The study enrolled a total of 388 recipients. Among them, acute allograft rejection was observed in 54 cases. We performed single nucleotide polymorphism genotyping of CD276, including rs11072431, rs11574495, rs12593558, rs12594627, rs2127015, rs3816661 and rs7176654, and TREML2, including rs4714431, rs6915083, rs7754593, and rs9394767 from preoperative peripheral blood genome DNA.

Results: We found rs2127015 of CD276, rs6915083 and rs7754593 of TREML2, and HBV infection as well were associated with acute rejection. And, rs2127015 influences CD276 expression. Moreover, we established a risk assessment model, composited by statistically proved risk factors.

Conclusion: By integrating both clinical and genetic variables, liver transplant recipients can be categorized into different risk groups, and might benefit from individualized therapies.

Keywords: CD276; SNP; acute rejection; costimulatory molecule; liver transplantation.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
LD plots of CD276 and TREML2. We identified two haplotype blocks, block 1 and block 2, in CD276, and one haplotype block, block 3, in TREML2
Figure 2
Figure 2
CD276 and TREML2 mRNA expression in PBMCs. Plots represented relative expression level of mRNA of each individual recipient. The result indicated that T allele carriers of rs2127015 expressed more CD276 mRNA than the others (p < 0.05). Bar represented mean ± standard deviation of the scatter plots
Figure 3
Figure 3
Membrane CD276 expression in CD3‐ PBMCs. Plots represented the percent of CD276 positive cells in CD3‐ PBMCs of each individual recipient. The result indicated that T allele carriers of rs2127015 possessed more CD276 + cell in CD3‐ peripheral blood (p < 0.05). Bar represented mean ± standard deviation of the scatter plots
Figure 4
Figure 4
Acute rejection model assessment with ROC curve
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