Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Departments of Medicine and Immunology, University of Manitoba and Shared Health Services Manitoba, Winnipeg, Manitoba, Canada.
Curr Opin Organ Transplant. 2020 Dec;25(6):536-542. doi: 10.1097/MOT.0000000000000811.
There is tremendous interest in understanding when, if, and how non-HLA antibodies contribute to allograft injury. Numerous non-HLA target antigens have been identified and sensitization to these targets have been associated with delayed allograft function, rejection, and allograft failure. This review focuses on the clinical utility of HLA antibody testing, highlighting the strengths and limitations of current clinical studies, and the need for defining characteristics to inform non-HLA antibody pathogenicity.
Clinical studies continue to show associations between non-HLA antibodies and rejection and reduced allograft survival across multiple transplanted organ types. The worst clinical outcomes continue to be observed among recipients testing positive for both non-HLA and donor-specific HLA antibodies. Mechanistic insights from both animal and clinical studies support a model in which tissue injury accompanied by an inflammatory environment influence non-HLA antibody formation and pathogenicity.
Immune triggers that lead to non-HLA antibody formation and pathogenicity are complex and poorly understood. The ability of non-HLA antibodies to mediate allograft injury may depend upon their affinity and strength (titer), target specificity, density of the target antigen, and synergy with donor-specific HLA antibodies.
人们非常有兴趣了解非 HLA 抗体何时、是否以及如何导致移植物损伤。已经鉴定出许多非 HLA 靶抗原，并且这些靶抗原的致敏与移植物功能延迟、排斥和移植物衰竭有关。本综述重点介绍了 HLA 抗体检测的临床应用，强调了当前临床研究的优势和局限性，以及需要确定特征来告知非 HLA 抗体的致病性。
临床研究继续显示，非 HLA 抗体与排斥反应和多种移植器官类型的移植物存活率降低之间存在关联。在同时检测到非 HLA 和供体特异性 HLA 抗体阳性的受者中，观察到最严重的临床结局。来自动物和临床研究的机制见解支持这样一种模型，即伴有炎症环境的组织损伤影响非 HLA 抗体的形成和致病性。
导致非 HLA 抗体形成和致病性的免疫触发因素复杂且了解甚少。非 HLA 抗体介导移植物损伤的能力可能取决于其亲和力和强度（效价）、靶特异性、靶抗原的密度以及与供体特异性 HLA 抗体的协同作用。
