Bartel Gregor, Wahrmann Markus, Exner Markus, Regele Heinz, Schillinger Martin, Hörl Walter H, Böhmig Georg A
Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Transplantation. 2007 Mar 27;83(6):727-33. doi: 10.1097/01.tp.0000256337.18347.aa.
The presence of preformed alloantibodies with the ability to activate complement may pose a particular risk for kidney allograft rejection. The aim of this study was to evaluate variables that determine the complement-fixing capability of human leukocyte antigen (HLA) sensitization.
Sixty-five sensitized patients with > or =10% pretransplant panel-reactive antibody (PRA) levels uncovered by immunoglobulin G [IgG]FlowPRA HLA class I and/or class II screening were included. Applying modified FlowPRA screening, sera were evaluated for patterns of alloreactive IgG subclasses and IgM, and, in parallel, for their complement-activating ability assessed by flow cytometric detection of human complement split product deposition ([C4d]FlowPRA).
Approximately two-thirds (68%) of tested sera were found to contain complement-fixing alloreactivity (> or =10%[C4d]FlowPRA). IgG1 type panel reactivity was predominant (detectable HLA class I and II reactivity in 93% and 91% of IgG-positive sera), followed by IgG3 (49%/44%), IgG2 (44%/27%), and IgG4 (19%/11%). Applying partial correlation we found an independent correlation of both %[IgG1]FlowPRA and %[IgG3]FlowPRA with %[C4d]FlowPRA reactivities (P< or =0.01). In addition, for IgG1 a contribution of the amount of bound alloantibody to complement-fixation was observed. Complement-fixation was also favored by the simultaneous presence of alloreactive IgG1, IgG3, and IgM. Previous grafting, but not pregnancy and transfusion, was independently associated with complement-fixing sensitization (P<0.05), presumably due to increased IgG1 type reactivity.
Anti-HLA antibody-triggered complement activation is dependent on both the pattern of Ig reactivities and the amount of bound antibody. Previous transplantation represents a major risk factor for the development of complement-fixing sensitization.
预先形成的具有激活补体能力的同种异体抗体的存在可能给肾移植排斥带来特殊风险。本研究的目的是评估决定人类白细胞抗原（HLA）致敏补体固定能力的变量。
纳入65例致敏患者，这些患者通过免疫球蛋白G[IgG]流式PRA HLA I类和/或II类筛查发现移植前群体反应性抗体（PRA）水平≥10%。应用改良的流式PRA筛查，评估血清中同种反应性IgG亚类和IgM的模式，并同时通过流式细胞术检测人补体裂解产物沉积（[C4d]流式PRA）评估其补体激活能力。
发现约三分之二（68%）的检测血清含有补体固定同种反应性（≥10%[C4d]流式PRA）。IgG1型群体反应性占主导（在93%和91%的IgG阳性血清中可检测到HLA I类和II类反应性），其次是IgG3（49%/44%）、IgG2（44%/27%）和IgG4（19%/11%）。应用偏相关分析，我们发现%[IgG1]流式PRA和%[IgG3]流式PRA与%[C4d]流式PRA反应性均独立相关（P≤0.01）。此外，对于IgG1，观察到结合的同种异体抗体量对补体固定有贡献。同种反应性IgG1、IgG3和IgM同时存在也有利于补体固定。既往移植，但非妊娠和输血，与补体固定致敏独立相关（P<0.05），可能是由于IgG1型反应性增加。
抗HLA抗体触发的补体激活既取决于Ig反应模式，也取决于结合抗体的量。既往移植是补体固定致敏发生的主要危险因素。
