Milongo David, Vieu Guillaume, Blavy Sarah, Del Bello Arnaud, Sallusto Federico, Rostaing Lionel, Kamar Nassim, Congy-Jolivet Nicolas
Department of Nephrology and Organ Transplantation, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France.
Laboratoire d'immunologie, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France; Laboratoire d'Immunogénétique Moléculaire, EA 3034, Université Toulouse III Paul-Sabatier, 118 Route de Narbonne, 31062 Toulouse, France.
Transpl Immunol. 2015 Jun;32(3):151-5. doi: 10.1016/j.trim.2015.04.004. Epub 2015 Apr 30.
Therapeutic antibodies used to desensitize patients awaiting a human leukocyte antigen (HLA) or ABO-mismatched graft are suspected to interfere with the lymphocytotoxicity crossmatch (LCT-XM) test when they are present in the tested sera because of their potential ability to activate or inhibit the complement.
The most frequent therapeutic antibodies (Abs) used in desensitization protocols (intravenous immunoglobulins, rituximab, basiliximab, eculizumab, antithymocyte globulin) were added to a negative- or a positive-control serum at various concentrations, and tested in vitro in a LCT-XM test.
Rituximab turned the LCT-XM positive on B cells at 0.2 μg/mL and antithymocyte globulin turned the LCT-XM positive with T and B cells at 20 μg/mL and 200 μg/mL, respectively. Treatment with dithiothreitol sera, supplemented with rituximab (0.2 and 2 μg/mL) and antithymocyte globulins (20 and 200 μg/mL), partially or totally reduced this positive interference. Intravenous immunoglobulin, eculizumab, and basiliximab did not trigger any interference with the negative control serum. In a positive LCT-XM, eculizumab did not annihilate activation of the rabbit complement. Intravenous immunoglobulins (25 g/L) could partially or totally reduced lysis score of positive crossmatch with weak lysis scores.
If eculizumab within the serum did not annihilate rabbit complement activation and basiliximab did not interfere with the crossmatch reaction, treatments based on rituximab, antithymocyte globulin and intravenous immunoglobulins need to be taken into account when interpreting a positive or negative crossmatch test.
用于使等待人类白细胞抗原（HLA）或ABO血型不匹配移植的患者脱敏的治疗性抗体，当它们存在于检测血清中时，由于其激活或抑制补体的潜在能力，被怀疑会干扰淋巴细胞毒性交叉配型（LCT-XM）试验。
将脱敏方案中最常用的治疗性抗体（静脉注射免疫球蛋白、利妥昔单抗、巴利昔单抗、依库珠单抗、抗胸腺细胞球蛋白）以不同浓度添加到阴性或阳性对照血清中，并在LCT-XM试验中进行体外测试。
利妥昔单抗在0.2μg/mL时使B细胞的LCT-XM呈阳性，抗胸腺细胞球蛋白在20μg/mL和200μg/mL时分别使T细胞和B细胞的LCT-XM呈阳性。用补充有利妥昔单抗（0.2和2μg/mL）和抗胸腺细胞球蛋白（20和200μg/mL）的二硫苏糖醇血清处理，部分或完全减少了这种阳性干扰。静脉注射免疫球蛋白、依库珠单抗和巴利昔单抗对阴性对照血清未产生任何干扰。在阳性LCT-XM中，依库珠单抗未消除兔补体的激活。静脉注射免疫球蛋白（25g/L）可部分或完全降低弱阳性交叉配型的裂解评分。
如果血清中的依库珠单抗未消除兔补体激活，且巴利昔单抗未干扰交叉配型反应，那么在解释阳性或阴性交叉配型试验结果时，需要考虑基于利妥昔单抗、抗胸腺细胞球蛋白和静脉注射免疫球蛋白的治疗方法。
