Histocompatibility and Immunogenetics Laboratory, Northwest London Pathology NHS Trust, Hammersmith Hospital, London, UK.
Imperial College Renal and Transplant Centre, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, Hammersmith Campus, London, UK.
Am J Transplant. 2024 Jul;24(7):1218-1232. doi: 10.1016/j.ajt.2024.02.019. Epub 2024 Feb 23.
Defining HLA mismatch at the molecular compared with the antigen level has been shown to be superior in predicting alloimmune responses, although data from across different patient populations are lacking. Using HLA-Matchmaker, HLA-EMMA and PIRCHE-II, this study reports on the association between molecular mismatch (MolMM) and de novo donor-specific antibody (dnDSA) in an ethnically diverse kidney transplant population receiving a steroid-sparing immunosuppression protocol. Of the 419 patients, 51 (12.2%) patients had dnDSA. De novo DSA were seen more frequently with males, primary transplants, patients receiving tacrolimus monotherapy, and unfavorably HLA-matched transplants. There was a strong correlation between MolMM load and antigen mismatch, although significant variation of MolMM load existed at each antigen mismatch. MolMM loads differed significantly by recipient ethnicity, although ethnicity alone was not associated with dnDSA. On multivariate analysis, increasing MolMM loads associated with dnDSA, whereas antigen mismatch did not. De novo DSA against 8 specific epitopes occurred at high frequency; of the 51 patients, 47 (92.1%) patients with dnDSA underwent a pretreatment biopsy, with 21 (44.7%) having evidence of alloimmune injury. MolMM has higher specificity than antigen mismatching at identifying recipients who are at low risk of dnDSA while receiving minimalist immunosuppression. Immunogenicity consideration is important, with more work needed on identification, especially across different ethnic groups.
与抗原水平相比，在分子水平上定义 HLA 不匹配已被证明可以更好地预测同种异体免疫反应，尽管缺乏来自不同患者群体的数据。本研究使用 HLA-Matchmaker、HLA-EMMA 和 PIRCHE-II，报告了在接受类固醇节约免疫抑制方案的种族多样化肾移植人群中，分子不匹配（MolMM）与新出现的供体特异性抗体（dnDSA）之间的关联。在 419 名患者中，有 51 名（12.2%）患者出现 dnDSA。dnDSA 更常见于男性、原发性移植、接受他克莫司单药治疗以及 HLA 匹配不佳的移植患者。MolMM 负荷与抗原不匹配之间存在很强的相关性，尽管在每个抗原不匹配时 MolMM 负荷存在显著差异。MolMM 负荷因受者种族而异，尽管种族本身与 dnDSA 无关。在多变量分析中，MolMM 负荷的增加与 dnDSA 相关，而抗原不匹配则没有。针对 8 个特定表位的新出现 DSA 发生率很高；在 51 名有 dnDSA 的患者中，47 名（92.1%）接受了预处理活检，其中 21 名（44.7%）有同种免疫损伤的证据。在接受极简免疫抑制治疗时，MolMM 比抗原错配在识别低 dnDSA 风险的受者方面具有更高的特异性。免疫原性考虑很重要，需要在不同种族群体中进行更多的鉴定工作。
