University Hospital of the Faculty of Medical Sciences, Belo Horizonte, Minas Gerais State, Brazil; Faculty of Medical Sciences, Belo Horizonte, Minas Gerais State, Brazil.
Faculty of Medical Sciences, Belo Horizonte, Minas Gerais State, Brazil; IMUNOLAB - Laboratory of Histocompatibility, Belo Horizonte, Minas Gerais State, Brazil.
Transpl Immunol. 2021 Jun;66:101390. doi: 10.1016/j.trim.2021.101390. Epub 2021 Apr 7.
The presence of donor-specific antibodies (DSAs) against HLA-DQB1 is considered a significant barrier to good outcome and allograft survival in kidney transplantation (KT). This study aimed to assess the impact of induction immunotherapy on the outcome and allograft survival in KT patients with HLA-DQB1-DSA.
Thirty-two patients who had undergone KT and found to be positive for HLA-DQB1-DSA were monitored at least one to 10 years. They were allocated into two groups of patients: G1 received induction immunotherapy (n = 14 patients; 43.75%), and G2 did not (n = 18 patients; 56.25%).
In G1, 6 (42.86%) patients experienced rejection episodes (RE), 2 (14.29%) due to antibody-mediated rejection (ABMR) and 4 (28.57%) due to T-cell-mediated rejection (TCMR). In G2, 13 (72.22%) patients experienced RE, 3 (16.67%) due to ABMR, and 10 (55.56%) due to TCMR. Graft loss occurred in 4 patients from G1, 2 (14.29%) due to ABMR and 2 (14.29%) due to non-immunological causes. In G2, 9 (50.00%) patients lost their grafts, 2 (11.11%) due to TCMR, 2 (11.11%) due to ABMR, and 5 (27.78%) due to non-immunological causes. The graft survival rate was 64.29% in G1 and 45.83% in G2. Glomerulitis and peritubular capillaritis were observed in 3 and C4d-positive patients with/or without induction who lost their grafts by ABMR by HLA-DQ DSA. Two patients from G2 lost their graft by TCMR due to interstitial lymphocytic infiltrate (i1), foci of mild tubulitis (t2), interstitial edema, moderate interstitial fibrosis and tubular atrophy. Better graft survival rates were shown in patients from G1 who received induction immunotherapy.
Our study suggests that patients with an immunological profile of HLA-DQ+ DSA+ treated by immunotherapy induction have a decreased risk of ABMR and increased allograft survival, and the presence of anti-HLA-DQB1 DSA+ detected before and after KT were associated with ABMR episodes and failure.
供体特异性抗体（DSA）针对 HLA-DQB1 的存在被认为是肾移植（KT）中良好结局和移植物存活的重要障碍。本研究旨在评估诱导免疫治疗对 HLA-DQB1-DSA 阳性 KT 患者结局和移植物存活的影响。
32 名接受 KT 并发现 HLA-DQB1-DSA 阳性的患者至少监测了 1 至 10 年。他们被分为两组患者：G1 接受诱导免疫治疗（n=14 例；43.75%），G2 未接受（n=18 例；56.25%）。
G1 中有 6 名（42.86%）患者发生排斥反应（RE），2 名（14.29%）为抗体介导的排斥反应（ABMR），4 名（28.57%）为 T 细胞介导的排斥反应（TCMR）。G2 中有 13 名（72.22%）患者发生 RE，3 名（16.67%）为 ABMR，10 名（55.56%）为 TCMR。G1 中有 4 名患者发生移植物丢失，2 名（14.29%）为 ABMR，2 名（14.29%）为非免疫原因。G2 中有 9 名（50.00%）患者失去移植物，2 名（11.11%）为 TCMR，2 名（11.11%）为 ABMR，5 名（27.78%）为非免疫原因。G1 组移植物存活率为 64.29%，G2 组为 45.83%。在接受 HLA-DQ DSA 诱导治疗后发生 ABMR 并失去移植物的 3 名和 C4d 阳性患者中，观察到肾小球肾炎和肾小管毛细血管炎。G2 中有 2 名患者因间质淋巴细胞浸润（i1）、轻度小管炎（t2）、间质水肿、中度间质纤维化和肾小管萎缩而失去移植物，发生 TCMR。接受诱导免疫治疗的 G1 患者显示出更好的移植物存活率。
本研究表明，接受免疫治疗诱导的 HLA-DQ+DSA+免疫患者发生 ABMR 的风险降低，移植物存活率增加，KT 前后检测到的抗 HLA-DQB1 DSA+与 ABMR 发作和失败相关。
