Gerrits Jeroen H, van de Wetering Jacqueline, Drabbels Jos J M, Claas Frans H J, Weimar Willem, van Besouw Nicole M
Department of Internal Medicine - Transplantation, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Nephrol Dial Transplant. 2008 Jun;23(6):2016-23. doi: 10.1093/ndt/gfm899. Epub 2007 Dec 22.
After HLA-identical living-related (LR) kidney transplantation, only non-HLA antigen mismatches between donor and recipient may exist. We questioned whether donor-reactive responses against non-HLA antigens could be found after HLA-identical LR kidney transplantation, and wondered whether donor reactivity in the HLA-identical setting was different from the HLA-mismatched setting during immunological quiescence. Healthy individuals served as controls.
Elispot assays were performed to determine the number of alloreactive IFN-gamma-producing cells (pc), IL-10 pc, granzyme B (GrB) pc and IL-13 pc from peripheral blood mononuclear cells (PBMC) of HLA-identical, HLA-mismatched LR kidney transplant recipients and healthy individuals.
The frequency of alloreactive IFN-gamma pc, IL-13 pc and GrB pc was higher in healthy individuals compared to both transplant patient groups. In the HLA-identical group, significantly higher numbers of donor-reactive IL-10 pc were found compared to their autologous control. These frequencies were also higher compared to the HLA-mismatched and healthy control group. The number of donor-reactive GrB pc was higher in the HLA-mismatched group than in the HLA-identical group. Donor-reactive IFN-gamma pc and IL-13 pc were comparable in both transplant groups.
In recipients of HLA-identical LR kidney transplant, high donor-reactive IL-10 pc, in combination with low donor-reactive IFN-gamma pc, IL-13 pc and GrB pc, suggests active downregulation of reactivity against non-HLA molecules.
在 HLA 配型相同的亲属活体肾移植后，供体与受体之间可能仅存在非 HLA 抗原错配。我们质疑在 HLA 配型相同的亲属活体肾移植后是否能发现针对非 HLA 抗原的供体反应性应答，并且想知道在免疫静止期，HLA 配型相同情况下的供体反应性是否与 HLA 错配情况下不同。健康个体作为对照。
进行酶联免疫斑点分析（Elispot 分析），以确定 HLA 配型相同、HLA 错配的亲属活体肾移植受者及健康个体外周血单个核细胞（PBMC）中产生同种异体反应性γ干扰素的细胞（pc）、白细胞介素 -10 pc、颗粒酶 B（GrB）pc 和白细胞介素 -13 pc 的数量。
与两个移植患者组相比，健康个体中同种异体反应性γ干扰素 pc、白细胞介素 -13 pc 和 GrB pc 的频率更高。在 HLA 配型相同组中，与自体对照相比，发现供体反应性白细胞介素 -10 pc 的数量显著更高。这些频率也高于 HLA 错配组和健康对照组。HLA 错配组中供体反应性 GrB pc 的数量高于 HLA 配型相同组。两个移植组中供体反应性γ干扰素 pc 和白细胞介素 -13 pc 相当。
在 HLA 配型相同的亲属活体肾移植受者中，高供体反应性白细胞介素 -10 pc 与低供体反应性γ干扰素 pc、白细胞介素 -13 pc 和 GrB pc 相结合，提示对非 HLA 分子的反应性存在主动下调。
