Leffell Mary S, Montgomery Robert A, Zachary Andrea A
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Clin Transpl. 2005:259-71.
Although it was established in the 1980's that positive crossmatches associated with adverse transplant outcomes were those due to HLA specific antibodies, the cell-based assays for determining antibody specificity were time consuming, laborious, and moderately specific and sensitive. Technological advances now permit much more rapid and thorough antibody characterization. While no single assay can identify all anti-HLA antibodies in a patient's serum, the repertoire of specificities that can be defined is impressive and continues to improve. By using complimentary assays, most predominant specificities can be defined in even very highly sensitized patients. Perhaps, more critical, the sensitivity of solid phase immunoassays, which in some cases surpasses that of cell-based flow cytometry, provides a new level of assurance in the detection of humoral sensitization. The impact of these changes in antibody testing is already being felt in transplantation, providing a better evaluation of the level and breadth of sensitization prior to transplantation and greatly facilitating the success of humoral desensitization protocols. Thorough antibody identification can also provide a "virtual crossmatch" or a profile of incompatible donors defined by unacceptable antigens. An approach using the frequencies of unacceptable antigens to derive the probability of incompatible donors will likely be a feature of revised renal allocation for sensitized patients in the US. A compelling body of data is also accumulating proving the efficacy of monitoring for the recurrence or de-novo production of anti-donor HLA specific antibodies after transplantation. The possibility of early detection of humoral rejection in time for effective clinical intervention may offer a means to combat the inexorable loss of grafts to chronic rejection. Looking further into the future, as extensive antibody definition and monitoring are more universally applied, the ability to rule out HLA specific antibodies as a cause of graft loss will certainly also help determine the role of non-HLA antibodies in the outcome of solid organ and hematopoietic stem cell transplantation.
尽管在20世纪80年代就已确定，与移植不良结果相关的阳性交叉配型是由HLA特异性抗体所致，但用于确定抗体特异性的基于细胞的检测方法耗时、费力，且特异性和敏感性一般。如今，技术进步使得抗体特征鉴定能够更快、更全面地进行。虽然没有一种检测方法能够识别患者血清中的所有抗HLA抗体，但能够确定的特异性种类令人印象深刻，并且还在不断改进。通过使用互补检测方法，即使是高度致敏的患者，也能确定大多数主要的特异性。或许更关键的是，固相免疫检测的敏感性在某些情况下超过了基于细胞的流式细胞术，为体液致敏检测提供了新的保障水平。这些抗体检测变化的影响在移植领域已经显现，能够在移植前更好地评估致敏的水平和广度，并极大地促进体液脱敏方案的成功。全面的抗体鉴定还可以提供“虚拟交叉配型”，即由不可接受抗原定义的不相容供体概况。利用不可接受抗原的频率来推导不相容供体概率的方法，可能会成为美国修订后的致敏患者肾脏分配方案的一个特点。越来越多令人信服的数据也在积累，证明了移植后监测抗供体HLA特异性抗体复发或新生的有效性。及时早期检测体液排斥以便进行有效临床干预的可能性，可能提供一种手段来对抗移植物因慢性排斥而不可避免的丧失。展望更远的未来，随着广泛的抗体定义和监测得到更普遍的应用，排除HLA特异性抗体作为移植物丢失原因的能力，肯定也将有助于确定非HLA抗体在实体器官和造血干细胞移植结果中的作用。
