背景:已经假设抗谷胱甘肽S-转移酶T1(GSTT1)抗体(abs)的存在是抗体介导的排斥(AMR)的致病因素。
方法:我们的目的是使用Immucor的非HLALuminex分析,在87例肾移植(KTx)患者的队列中评估GSTT1,抗GSTT1ab和AMR的遗传变异之间的关系。根据活检证实的AMR和HLA-DSA状态对患者进行分类:抗HLA-DSA阳性的AMR(AMR/DSA+,n=29),AMR但未检测到抗HLA-DSA(AMR/DSA-,n=28)和同种异体移植功能稳定且无排斥反应的对照患者(n=30)。
结果:在MFI截止值为3000时,抗GSTT1abs的总患病率为18.3%。抗GSTT1abs的患者比例在AMR/DSA-组中较高(25%),与对照组(13.3%)和AMR/DSA组(3.4%)相比(p=0.06)。在抗GSTT1ab的患者中,AMR/DSA-和GSTT1-Null患者的MFI较高.在81例接受GSTT1基因分型的患者中,19.8%是无效等位基因(GSTT1-Null)的纯合子。移植受者的GSTT1-Null状态与抗GSTT1ab的发展有关(OR,4.49;95CI,1.2-16.7)。此外,GSTT1-Null基因型(OR26.01;95CI,1.63-404)和抗GSTT1ab阳性(OR14.8;95CI,1.1-190)与AMR相关。在AMR/DSA患者中,在研究观察期内,抗GSTT1ab的存在并未导致较高的失败风险.
结论:抗GSTT1abs和GSTT1-Null基因型的存在与AMR相关,但在这一早期同种异体移植损伤变化队列中,似乎不会导致加速的移植物损伤,有限的随访期。
The presence of anti-Glutathione S-transferase T1 (GSTT1) antibodies (abs) has been hypothesized as a pathogenic contributor in antibody-mediated rejection (AMR).
We aimed to evaluate the relationship between genetic variants of GSTT1, anti-GSTT1 abs and AMR in a cohort of 87 kidney transplant (KTx) patients using Immucor\'s non-HLA Luminex assay. Patients were classified according to biopsy-proven AMR and HLA-DSA status: AMR with positive anti-HLA-DSAs (AMR/DSA+, n = 29), AMR but no detectable anti-HLA-DSAs (AMR/DSA-, n = 28) and control patients with stable allograft function and no evidence of rejection (n = 30).
At an MFI cut-off of 3000, the overall prevalence of anti-GSTT1 abs was 18.3%. The proportion of patients with anti-GSTT1 abs was higher in the AMR/DSA- group (25%), compared to the control (13.3%) and AMR/DSA+ group (3.4%) (p = 0.06). Among patients with anti-GSTT1 abs, the MFI was higher in AMR/DSA- and GSTT1-Null patients. Of 81 patients who underwent GSTT1 genotyping, 19.8% were homozygotes for the null allele (GSTT1-Null). GSTT1-Null status in the transplant recipients was associated with the development of anti-GSTT1 abs (OR, 4.49; 95%CI, 1.2-16.7). In addition, GSTT1-Null genotype (OR 26.01; 95%CI, 1.63-404) and anti-GSTT1 ab positivity (OR 14.8; 95%CI, 1.1-190) were associated with AMR. Within AMR/DSA- patients, the presence of anti-GSTT1 abs didn\'t confer a higher risk of failure within the study observation period.
The presence of anti-GSTT1 abs and GSTT1-Null genotype is associated with AMR, but do not appear to lead to accelerated graft injury in this cohort of early allograft injury changes, with a limited period of follow-up.