ABO血型基因与移植肾急性排斥反应相关性的研究

Association of ABO genotype with acute rejection in renal transplantation

目的 探讨ABO血型基因与移植肾急性排斥反应（AR）的相关性.方法 采用引物特异性聚合酶链式反应（PCR-SSP）技术检测2009年5月至2010年2月87例肾移植受者及其对应的48例供者ABO（A1、A2、B、O1、O2）血型基因,分析供受者ABO血型基因相合组与错配组受者AR发生、治疗及转归情况.结果 PCR-SSP测定ABO血型基因推定的表型和血清学方法测定ABO血型表型完全相符.供受者ABO血型基因相合组受者50例,发生AR 6例,经甲泼尼龙（MP）冲击治疗后临床逆转.ABO血型基因错配组受者37例,发生AR 11例,经MP冲击治疗后,临床逆转10例,周期性反复发生AR 1例.错配组与相合组受者AR发生率差异有统计学意义（29.7%与12.0%,P〈0.05）.错配组1例A2O1血型基因受者接受A1O1血型基因供肾后,受者血清检测发现抗A1抗体,抗体效价IgG 1：64,IgM 1：16,移植术后3～10个月周期性反复发生AR,且周期逐渐变短,激素疗效逐渐降低,术后1年SCr达441μmol/L.结论 检测供受者HLA时同步检测ABO血型基因具有很强的可行性.A2血型基因受者适宜选择O型供肾.供受者ABO血型基因错配是介导肾移植术后AR的危险因素,检测供受者ABO血型基因,降低ABO血型基因错配率对预防AR有一定的临床意义.

Objective To investigate a possible association of donor-recipient compatibility for ABO blood group alleles with acute rejection （AR） in renal transplantation. Methods A study comprising 87 pairs of donor and recipient was performed. The ABO genotype A1, A2, O1, O2, and B alleles of renal transplanted recipients and their respective donors were assessed by PCR amplification with sequence-specific primers （PCR-SSP）. Accordingly, recipients were divided into donor-recipient ABO genotype matched and mismatched groups. Results The PCR-SSP based types of all cases showed total concordance with their serologically assigned ABO groups. Fifty pairs （57. 5%） were matched for ABO genotype among the 87 pairs of donor and recipient while 37 （42. 5%） were mismatched, including 1 allele mismatch in 31 pairs （83.8%）, 2 alleles mismatches in 6 pairs （16. 2%）.The incidence of AR was 12.0% （6 cases） and 29. 7% （11 cases） for ABO genotype matched and mismatched transplant patients, respectively （ P 〈 0.05）. After high dose methylprednisolone （MP）treatment, all cases exepienced reversion of AR except a A2O1 recipient receiving kidney from a A1O1enced 4 AR episodes within 3-10 months, and the period of AR was gradually shortened. After high dose MP was administered empirically, even though short-term improvement of renal function was observed, the serum creatinine continued to increase progressively with decreased efficacy of high dose MP. One year after operation the serum creatinine rose to 441 μmol/L. Conclusions Simultaneous definition of the ABO genotype and HLA is highly feasible. The A2 patient is suitable for receiving kidneys from blood group O donors. DNA mismatch for ABO genotype of renal transplant recipients and their respective donors is an independent risk factor for AR. Genotyping of ABO blood group is conducive to prevent AR.