(Introduction) Previous studies found that preferential accumulation of regulatory T (Treg) cells in the liver allografts during acute cellular rejection (ACR) was associated with less severity of rejection, suggesting a role of Treg cells in preventing excessive progress of ACR. We investigated the impact of single nucleotide polymorphisms (SNPs) of Forkhead box P3 (FOXP3) gene, a master regulator gene of Treg cells, on the severity of ACR in liver transplantation (LT) recipients.

(Method) A total of 102 living donor LT patients were enrolled in this study and categorized into no rejection, steroid sensitive acute rejection (SSAR) and steroid resistant acute rejection (SRAR). Genotyping of FOXP3 SNPs -3499 A/G (rs3761547), -3279 A/C (rs3761548) and -924 A/G (rs2232365) was performed using polymerase chain reaction restriction fragment length polymorphism technique (PCR-RFLP) technique.

(Result) Eighteen of the 102 (17.64%) patients experienced ACR within 6 weeks after LDLT. Consistent with the incidence of SRAR in previous reports, four of the 18 (22.22%) patients suffering ACR were diagnosed as having SRAR. One of the four were treated with OKT3 and the other three patients were treated with ATG. We did not find any statistical association between the FOXP3 SNPs genotype frequencies and the incidence of ACR. However, significantly higher incidence of SRAR was observed in the LT patients with FOXP3 rs3761548 A/C+A/A genotype than those with C/C genotype (A/C+A/A vs C/C; no rejection, SSAR, SRAR, 82.86%, 5.71%, 11.43% vs 82.09%, 17.91%, 0%, respectively, p=0.0063). The total dose of intravenous methylprednisolone used for ACR treatment was significantly higher in the rs3761548 A/C+A/A genotype than that in the C/C genotype (2037.5±887.5 gm vs 906.3±377.4 gm, p=0.005). The MLR assay performed at the time of diagnosing ACR showed significantly higher anti-donor alloimmune index in patients carrying rs3761548 A/C+A/A genotype compared to those with C/C genotype (71.4±94.5 vs 6.34±5.89, p=0.039). No significant association was observed between the incidence of SRAR and either rs3761547A/G or rs2232365 A/G SNPs.

(Conclusion) Our findings indicate that FOXP3 SNP rs3761548 A/C might be a predisposing factor for SRAR after LT.

CITATION INFORMATION: Tanaka Y, Sapana V, Ohdan H. FOXP3 rs3761548 A/C+A/A Genotype Is a Risk Factor for Steroid Resistant Rejection After Liver Transplantation. Am J Transplant. 2017;17 (suppl 3).

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