Kao K J
Department of Pathology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville 32610.
Blood. 1992 Dec 1;80(11):2931-7.
Recent technologic advancement enables us to prepare leukocyte-depleted or UVB-irradiated platelet concentrates for possible prevention of primary HLA alloimmunization. However, it is yet not known which of these two approaches is more efficacious. Because well-controlled studies cannot be easily conducted in human subjects to answer this question, a series of experiments were performed using a mouse transfusion model. The results showed that 100% of CBA mice with H2k haplotype developed antibody to donor H2d major histocompatibility complex (MHC) antigens after two weekly transfusions of platelet concentrates containing 2000 leukocytes/microL. In contrast, only 50% of the mice became alloimmunized after receiving platelets containing < or = 2 leukocytes/microL. More impressively, none developed anti-H2d antibodies after receiving two platelet concentrates irradiated with 1,200 mJ/cm2 UVB. UVB irradiation was found to be equally effective in reducing the alloantigenicity of platelet concentrates regardless of whether they contained more than a fully immunogenic dose of leukocytes. The antibody titers determined after five weekly transfusions also supported the observation that UVB irradiation was more efficacious than a 3-log leukocyte depletion in the prevention of primary alloimmunization to MHC antigens. In addition, the studies showed that only transfusions of UVB-irradiated platelet products could induce the suppression of immunologic responses to donor MHC antigens in recipients and the induced immunologic suppression could not be further enhanced by gamma irradiation or by leukocyte depletion.
最近的技术进步使我们能够制备白细胞去除或紫外线B(UVB)照射的血小板浓缩物,以预防原发性人类白细胞抗原(HLA)同种免疫。然而,目前尚不清楚这两种方法中哪一种更有效。由于难以在人体受试者中进行严格对照的研究来回答这个问题,因此使用小鼠输血模型进行了一系列实验。结果显示,在每周两次输注含有2000个白细胞/微升的血小板浓缩物后,100%具有H2k单倍型的CBA小鼠产生了针对供体H2d主要组织相容性复合体(MHC)抗原的抗体。相比之下,在接受含有≤2个白细胞/微升的血小板后,只有50%的小鼠发生了同种免疫。更令人印象深刻的是,在接受两次用1200 mJ/cm2 UVB照射的血小板浓缩物后,没有小鼠产生抗H2d抗体。发现UVB照射在降低血小板浓缩物的同种抗原性方面同样有效,无论它们是否含有超过完全免疫原性剂量的白细胞。在每周输注五次后测定的抗体滴度也支持了以下观察结果:在预防对MHC抗原的原发性同种免疫方面,UVB照射比3-log级的白细胞去除更有效。此外,研究表明,只有输注UVB照射的血小板制品才能诱导受者对供体MHC抗原的免疫反应受到抑制,并且γ射线照射或白细胞去除不能进一步增强所诱导的免疫抑制。