Baldwin W M, Paul L C, Claas F H, Daha M R
Prog Clin Biol Res. 1986;224:41-67.
Clearly the pioneering studies on hyperacute rejection, which lead to the concept of antibody-mediated injury to transplants, still present challenges to the clinician today. It is obvious that tests for antibodies before and after transplantation must be further refined to more reliably distinguish among destructive, protective and innocuous antibodies. The current crossmatch tests detect antibodies to donor lymphocytes, but lymphocytes may not always represent adequately the antigenic composition of the tissue that will be transplanted. Moreover the distribution of antigens in transplanted tissues must be considered in relation to the functional anatomy of the organs in order to understand the ultimate effects of antibodies on specific transplants. Thus some antibodies that produce a positive crossmatch may be safely ignored because they exert either a beneficial or no effect on the organ that is to be transplanted, while other antibodies that remain undetected by crossmatches on lymphocytes may damage some types of transplants. Moreover, the balance between protective and destructive antibodies is not dynamic; with time potentially dangerous antibody responses may be inhibited by a variety of autoregulatory mechanisms, some of which may be mediated by antibodies. Regulatory as well as cytotoxic antibody production may be actively stimulated by pretransplant blood transfusions. These antibody-mediated immune responses probably are magnified in the clinical setting by our current therapeutic immunosuppressive drugs which have more impact on cell-mediated immunity than on antibody-mediated mechanisms. New immunosuppressive interventions devised to inhibit undesired antibody-mediated immune responses might be of benefit to those patients who fail to respond to current rejection therapy as well as to patients who have pre-existing antibodies and are waiting for transplants.
显然，关于超急性排斥反应的开创性研究，催生了抗体介导移植损伤的概念，至今仍给临床医生带来挑战。很明显，移植前后的抗体检测必须进一步完善，以便更可靠地区分具有破坏性、保护性和无害性的抗体。目前的交叉配型试验检测针对供体淋巴细胞的抗体，但淋巴细胞可能并不总能充分代表将要移植组织的抗原组成。此外，为了理解抗体对特定移植器官的最终影响，必须结合器官的功能解剖结构来考虑移植组织中抗原的分布。因此，一些产生阳性交叉配型结果的抗体可能可以安全地忽略，因为它们对将要移植的器官要么产生有益作用，要么没有影响，而其他在淋巴细胞交叉配型中未被检测到的抗体可能会损害某些类型的移植器官。此外，保护性抗体和破坏性抗体之间的平衡并非动态的；随着时间推移，潜在危险的抗体反应可能会受到多种自身调节机制的抑制，其中一些可能由抗体介导。移植前输血可能会积极刺激调节性抗体以及细胞毒性抗体的产生。在临床环境中，我们目前的治疗性免疫抑制药物可能会放大这些抗体介导的免疫反应，这些药物对细胞介导免疫的影响比对抗体介导机制的影响更大。设计用于抑制不良抗体介导免疫反应的新型免疫抑制干预措施，可能会对那些对当前排斥治疗无反应的患者以及那些已有抗体并等待移植的患者有益。
