Snanoudj Renaud, Beaudreuil Séverine, Arzouk Nadia, de Preneuf Hélène, Durrbach Antoine, Charpentier Bernard
Nephrology and Transplantation Department, Kremlin-Bicêtre Hospital, Le Kremlin-Bicêtre, France.
Transplantation. 2005 Feb 15;79(3 Suppl):S33-6. doi: 10.1097/01.tp.0000153298.48353.a4.
After delayed-type hypersensitivity and T cell cytotoxicity, the production of alloantibodies is the third effector mechanism contributing to graft injury. Histological characterization of antibody-mediated rejection and the detection of donor-reactive antibodies have highlighted the role of humoral immunity in acute and chronic rejection. A potential way of achieving central B cell tolerance is to induce complete chimerism with a myeloablative regimen and bone marrow transplant. However, nonmyeloablative regimens have been developed to create a state of "mixed chimerism" in patients without hematologic malignancies. Other strategies targeting B cells have been developed for the management of "high risk" clinical situations, including highly sensitized patients and transplantation with a positive crossmatch. These strategies have been extended to ABO incompatible transplantations and xenotransplantations. We will review therapeutic regimens that allow the removal or neutralization of pathogenic antibodies (immunoadsorption, plasmapheresis, intravenous globulins) and the blockade of memory B cell proliferation and differentiation into plasmocytes, including cyclophosphamide, the tacrolimus/mycophenolate mofetil combination, and anti-CD20 antibodies.
在迟发型超敏反应和T细胞细胞毒性之后，同种异体抗体的产生是导致移植物损伤的第三种效应机制。抗体介导排斥反应的组织学特征以及供体反应性抗体的检测突出了体液免疫在急性和慢性排斥反应中的作用。实现中枢B细胞耐受的一种潜在方法是通过清髓方案和骨髓移植诱导完全嵌合。然而，已经开发出非清髓方案以在没有血液系统恶性肿瘤的患者中创造“混合嵌合”状态。针对B细胞的其他策略已被开发用于管理“高风险”临床情况，包括高度致敏患者和交叉配型阳性的移植。这些策略已扩展到ABO血型不相容移植和异种移植。我们将回顾能够去除或中和致病性抗体的治疗方案（免疫吸附、血浆置换、静脉注射球蛋白）以及阻断记忆B细胞增殖和分化为浆细胞的治疗方案，包括环磷酰胺、他克莫司/霉酚酸酯组合以及抗CD20抗体。
