Seitz Adrienne, Mounsey Katherine, Hughes Pamela, Cullen Katherine, Welberry Smith Matthew, Daga Sunil, Carter Clive, Clark Brendan, Baker Richard
Renal Transplant Unit, St James's University Hospital, Leeds, UK.
Transplant Immunology, St James's University Hospital, Leeds, UK.
Kidney Int Rep. 2022 Aug 3;7(10):2251-2263. doi: 10.1016/j.ekir.2022.07.014. eCollection 2022 Oct.
The importance of donor-specific antibodies (DSAs) in renal transplantation has long been recognized, but the significance of human leukocyte antigen (HLA)-DP antibodies remains less clear. We performed a retrospective single center study of renal transplants with pre-existing isolated HLA-DP-DSAs to assess clinical outcomes.
Twenty-three patients with isolated HLA-DP-DSAs were compared with 3 control groups as follows: standard immunological risk (calculated reaction frequency [cRF] < 85%, no current or historical DSA, no repeat mismatched antigens with previous transplants, = 46), highly sensitized (cRF > 85%, = 27), and patients with HLA-DP antibodies that were not donor-specific ( = 18). Univariate and multivariate analyses were performed comparing antibody-mediated rejection (ABMR)-free and graft survival. Factors in the final multivariable models included patient group, % cRF, B-cell flow crossmatch (BFXM) positivity and regrafts.
Over a median follow-up of 1197 days, 65% of HLA-DP-DSA patients had ABMR on indication biopsies, and 30% of HLA-DP-DSA patients lost their graft. Pre-existing HLA-DP DSAs remained the single factor associated with ABMR after multivariable analysis (hazard ratio [HR] = 9.578, = 0.012). Patients with HLA-DP DSAs had increased microvascular scores ( = 0.0346) and worse transplant glomerulopathy ( = 0.015) on biopsy compared with the standard immunological risk group. Furthermore, flow crossmatch (FXM) positivity did not help inform on the risk of graft failure or ABMR in patients with preformed DP-DSA.
Transplants with pre-existing HLA-DP-DSAs should be considered high risk. Routine laboratory tests are unable to further risk stratify these patients. Recipients should be considered for intensified immunosuppression and closely monitored.
供体特异性抗体（DSA）在肾移植中的重要性早已得到认可，但人类白细胞抗原（HLA）-DP抗体的意义仍不太明确。我们对预先存在孤立性HLA-DP-DSA的肾移植患者进行了一项回顾性单中心研究，以评估临床结局。
将23例孤立性HLA-DP-DSA患者与3个对照组进行比较，如下：标准免疫风险（计算反应频率[cRF]<85%，无当前或既往DSA，与既往移植无重复错配抗原，n = 46）、高敏（cRF>85%，n = 27），以及具有非供体特异性HLA-DP抗体的患者（n = 18）。进行单因素和多因素分析，比较无抗体介导排斥反应（ABMR）和移植物存活情况。最终多变量模型中的因素包括患者组、cRF百分比、B细胞流式交叉配型（BFXM）阳性和再次移植。
在中位随访1197天期间，65%的HLA-DP-DSA患者在指征活检时发生ABMR，30%的HLA-DP-DSA患者移植肾失功。多因素分析后，预先存在的HLA-DP DSA仍然是与ABMR相关的单一因素（风险比[HR]=9.578，P = 0.012）。与标准免疫风险组相比，HLA-DP DSA患者活检时微血管评分增加（P = 0.0346），移植肾小球病更严重（P = 0.015）。此外，流式交叉配型（FXM）阳性无助于判断预先形成DP-DSA患者的移植肾失败或ABMR风险。
预先存在HLA-DP-DSA的移植应被视为高风险。常规实验室检查无法对这些患者进一步进行风险分层。应考虑对受者加强免疫抑制并密切监测。
