Department of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 1N4.
Bone Marrow Transplant. 2013 Jan;48(1):105-14. doi: 10.1038/bmt.2012.99. Epub 2012 Jun 4.
Anti-thymocyte globulin (ATG) is polyclonal, containing Ab specificities capable of binding to various immune-cell subsets implicated in the pathogenesis of GVHD, including T cells, B cells, natural killer cells, monocytes/macrophages, neutrophils and DC. We wished to determine which ATG specificities are important for GVHD prevention. We measured day 7 serum levels of 23 ATG specificities in 120 hematopoietic cell transplant recipients whose myeloablative conditioning included 4.5 mg/kg ATG (thymoglobulin). High levels of ATG specificities capable of binding to T- and B-cell subsets were associated with a low likelihood of acute GVHD (aGVHD). High levels of these ATG specificities were associated with increased rates of viral but not bacterial or fungal infections. They were not associated with an increased risk of malignancy relapse; on the contrary, high levels of ATG specificities capable of binding to regulatory T cells and invariant NKT cells were associated with a low risk of relapse. In conclusion, high levels of ATG antibodies to Ag(s) expressed on T and B cells are associated with a low risk of aGVHD and a high risk of viral but not bacterial or fungal infections. These antibodies have neutral or beneficial effects on relapse.
抗胸腺细胞球蛋白（ATG）是多克隆的，包含能够结合到参与 GVHD 发病机制的各种免疫细胞亚群的 Ab 特异性，包括 T 细胞、B 细胞、自然杀伤细胞、单核细胞/巨噬细胞、中性粒细胞和 DC。我们希望确定哪些 ATG 特异性对于预防 GVHD 很重要。我们在 120 例接受含 4.5mg/kg ATG（thymoglobulin）的清髓性预处理的造血细胞移植受者中测量了第 7 天的 23 种 ATG 特异性的血清水平。能够结合 T 细胞和 B 细胞亚群的高水平 ATG 特异性与急性 GVHD（aGVHD）的低可能性相关。这些 ATG 特异性的高水平与病毒感染率的增加相关，但与细菌或真菌感染率的增加无关。它们与恶性肿瘤复发的风险增加无关；相反，能够结合调节性 T 细胞和不变自然杀伤 T 细胞的 ATG 特异性的高水平与复发风险低相关。总之，高水平的 ATG 抗体针对 T 和 B 细胞上表达的 Ag(s)与 aGVHD 的低风险和病毒感染但无细菌或真菌感染的高风险相关。这些抗体对复发具有中性或有益的作用。
