Auffermann-Gretzinger Susanne, Eger Lars, Schetelig Johannes, Bornhäuser Martin, Heidenreich Falk, Ehninger Gerhard
Medizinische Klinik und Poliklinik I Universitätsklinikum Dresden, Dresden, Germany.
Transplantation. 2007 May 15;83(9):1268-72. doi: 10.1097/01.tp.0000260433.86776.ec.
The antibody alemtuzumab (anti-CD52) is effective in preventing acute graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (aHSCT). As well as depleting donor T cells, alemtuzumab may also work by targeting host dendritic cells (DC). To determine whether this second mechanism of action is significant, we investigated the effects of intravenous alemtuzumab by comparing skin and blood DC numbers of patients with chronic lymphocytic leukemia, before and after a 4-week course of alemtuzumab treatment. Although skin DC express CD52, the epitope is only weakly detectable and their numbers were not consistently reduced by alemtuzumab. In contrast, circulating blood DC, with stronger CD52 expression, were invariably diminished by alemtuzumab. Because DC depletion in the transplant recipient remains a promising approach for GvHD prophylaxis and therapy, more potent techniques, such as an antibody of different specificity, may be required for effective DC eradication in GvHD target organs.
抗CD52抗体阿仑单抗在预防异基因造血干细胞移植(aHSCT)后的急性移植物抗宿主病(GvHD)方面有效。除了消耗供体T细胞外,阿仑单抗还可能通过靶向宿主树突状细胞(DC)发挥作用。为了确定这第二种作用机制是否重要,我们通过比较阿仑单抗治疗4周疗程前后慢性淋巴细胞白血病患者的皮肤和血液DC数量,研究了静脉注射阿仑单抗的效果。虽然皮肤DC表达CD52,但该表位仅能微弱检测到,且阿仑单抗并未持续减少其数量。相比之下,CD52表达较强的循环血液DC总是会被阿仑单抗减少。由于移植受者体内DC的消耗仍然是预防和治疗GvHD的一种有前景的方法,可能需要更有效的技术,如不同特异性的抗体,才能在GvHD靶器官中有效清除DC。