van der Straaten Hanneke M, Fijnheer Rob, Nieuwenhuis H Karel, van de Winkel Jan G J, Verdonck Leo F
Department of Haematology, University Medical Center Utrecht, The Netherlands.
Biol Blood Marrow Transplant. 2005 Mar;11(3):206-12. doi: 10.1016/j.bbmt.2004.12.331.
Graft-versus-host disease (GVHD) is a serious complication of allogeneic stem cell transplantation for hematologic diseases. Antigen mismatches due to polymorphic differences between the patient and donor are central in the mechanisms of GVHD. Polymorphisms are known for FcgammaRIIa, and this molecule is present on endothelial, dendritic, and Langerhans cells. Donor cells reacting against the patient as GVHD can also react against the malignancy of the patient, and this is known as the graft-versus-leukemia (GVL) effect. Because the FcgammaRIIa molecule is also present on acute myeloid leukemia (AML) cells, an FcgammaRIIa mismatch could be a target for both GVHD and GVL. We retrospectively studied 73 AML patients and analyzed the differences in GVHD and relapse incidence between patients with and without a pro-GVHD/GVL FcgammaRIIa allotype mismatch. We observed a difference in FcgammaRIIa receptors with a pro-GVHD/GVL mismatch in 18 patient/donor pairs (25%). Univariate and multivariate analyses demonstrated the pro-GVHD mismatch to be a significant risk factor for the development of acute GVHD. There was no effect on the occurrence of chronic GVHD. The relapse incidence was not significantly different for patients with or without the pro-GVL mismatch, although there was a trend for fewer relapses in standard-risk AML patients with the pro-GVL mismatch. We conclude that the polymorphism of the FcgammaRIIa receptor may be a candidate target for acute GVHD.
移植物抗宿主病（GVHD）是血液系统疾病异基因干细胞移植的一种严重并发症。患者与供体之间由于多态性差异导致的抗原错配是GVHD发病机制的核心。FcγRIIa存在多态性，该分子存在于内皮细胞、树突状细胞和朗格汉斯细胞上。作为GVHD对患者产生反应的供体细胞也可能对患者的恶性肿瘤产生反应，这就是所谓的移植物抗白血病（GVL）效应。由于FcγRIIa分子也存在于急性髓系白血病（AML）细胞上，FcγRIIa错配可能是GVHD和GVL的共同靶点。我们回顾性研究了73例AML患者，分析了存在和不存在促GVHD/GVL FcγRIIa同种异型错配的患者之间GVHD和复发率的差异。我们在18对患者/供体（25%）中观察到具有促GVHD/GVL错配的FcγRIIa受体存在差异。单因素和多因素分析表明，促GVHD错配是急性GVHD发生的一个重要危险因素。对慢性GVHD的发生没有影响。存在或不存在促GVL错配的患者复发率没有显著差异，尽管具有促GVL错配的标准风险AML患者的复发趋势较少。我们得出结论，FcγRIIa受体的多态性可能是急性GVHD的一个潜在靶点。
