Session Time: 2:15pm-3:45pm
Presentation Time: 3:15pm-3:27pm
Location: Room 120-ABC
Aim- Acute cellular rejection (ACR) accounts for 15-25% of graft failure in living donor liver transplantation (LDLT). T regulatory cells (Treg) play an important role in regulation of T cell activation during allo-immune response after Liver Transplantation (LT). Forkhead box P3 (FoxP3) is well known as a master gene of Treg. However, no reports have so far shown that Foxp3 gene polymorphism affect the Treg function in allo-immune response. Therefore, we investigated the Foxp3 gene polymorphism in LDLT recipients and evaluated the potential impact on the severity of acute cellular rejection (ACR).
Methods: We enrolled 93 consecutive patients who underwent LDLT. Rs3761548 (A/C) variant allele in Foxp3 gene was genotyped by using PCR-RFLP technique. To monitor alloimmune responses, multiparameter mixed lymphocyte reaction (MLR) assay, wherein the number and phenotype of alloreactive precursors are quantified by combining CFSE-labeling and FCM analyses was performed pre and post LT. The clinical severity of ACR was categorized in accordance with response to anti-ACR treatments; i.e. the cases in which the accumulated dose of methylprednisolone for 3 days was over 500 mg but less than 1000 mg for curing ACR, were defined as mild ACR, whereas the cases in which that was over 1000 mg or thymoglobulin was used, were defined as severe ACR.
Results: Among the 93 LT recipients, 32 patients (34.4%) were Foxp3 [-3279A/A, A/C], which causes defective transcription of Foxp3 gene, whereas 61 patients (65.6%) were Foxp3 [-3279C/C], which leads to competent transcription of Foxp3 gene. In the 32 patients with Foxp3 [-3279A/A, A/C], 6 patients suffered from severe ACR (18.8%*), but none encountered mild ACR. In the 61 patients with Foxp3 [3279C/C], only one patient suffered from severe ACR (1.6%, P-0.0006*), while 10 patients encountered mild ACR (16.4%). The MLR assay revealed that stimulation indexes (S.I.) of both CD4+ and CD8+ T cells in responses to anti-donor stimulation at the time of diagnosing ACR were higher in patients with Foxp3 [-3279A/A, A/C] (8.2±4.7 and 6.1±5.8, respectively) in comparison with that in patients with Foxp3 [-3279C/C] (4.9±9.7 and 3.1±2.4, respectively).
Conclusions: There was strong association between Foxp3 gene SNP (Rs3761548) and severe ACR in the recipients of LDLT. Rs3761548 A carriers have an exacerbation risk of ACR once it occurs.
To cite this abstract in AMA style:Verma S, Tanaka Y, Shimizu S, Das L, Ohdan H. The Significant Association Between the Functional Polymorphism (Rs3761548) of Foxp3 Gene and the Severity of Acute Cellular Rejection in Liver Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/the-significant-association-between-the-functional-polymorphism-rs3761548-of-foxp3-gene-and-the-severity-of-acute-cellular-rejection-in-liver-transplantation/. Accessed December 1, 2020.
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