The Research Laboratory, Bonfils Blood Center, Denver, CO, USA; Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO, USA; Department of Surgery, School of Medicine, University of Colorado Denver, Aurora, CO, USA.
Vox Sang. 2014 Jul;107(1):76-82. doi: 10.1111/vox.12129. Epub 2013 Dec 30.
Transfusion-related acute lung injury (TRALI) is the most common cause of transfusion-related mortality and has been linked to the infusion of donor antibodies directed against recipient HLA class I antigens. We hypothesize that antibodies against HLA class I antigens bind to the antigens on the neutrophil (PMN) surface and induce priming and PMN cytotoxicity as the second event in a two-event in vitro model of PMN-mediated cytotoxicity.
Isolated PMNs from HLA-A2 homozygotes, heterozygotes and null donors were incubated with a monoclonal antibody to HLA-A2 and a human polyclonal IgG to HLA-A2 and priming of the oxidase was measured. The monoclonal antibodies and PMNs from these three groups were then used in a two-event model of PMN cytotoxicity.
The antibodies to HLA-A2 both primed PMNs from HLA-A2 homozygotes but not from heterozygotes or nulls. Antibodies to HLA-A2 also served as the second event in a two-event model to induce PMN cytotoxicity of HLA-A2 homozygous PMNs.
Antibodies to HLA class I antigens may directly prime/activate PMNs through the ligation of the antigen on the cell surface, and the antigen density appears to be important for these changes in PMN physiology.
输血相关性急性肺损伤（TRALI）是输血相关死亡的最常见原因，与输注针对受者 HLA Ⅰ类抗原的供体抗体有关。我们假设针对 HLA Ⅰ类抗原的抗体与中性粒细胞（PMN）表面的抗原结合，并在体外 PMN 介导的细胞毒性的两事件模型中作为第二个事件诱导 PMN 的致敏和细胞毒性。
用针对 HLA-A2 的单克隆抗体和针对 HLA-A2 的人多克隆 IgG 孵育来自 HLA-A2 纯合子、杂合子和缺失供体的分离 PMN，并测量氧化酶的致敏。然后将来自这三组的单克隆抗体和 PMN 用于 PMN 细胞毒性的两事件模型。
针对 HLA-A2 的抗体均可致敏 HLA-A2 纯合子的 PMN，但不能致敏杂合子或缺失供体的 PMN。针对 HLA-A2 的抗体也作为第二个事件在两事件模型中诱导 HLA-A2 纯合子 PMN 的细胞毒性。
针对 HLA Ⅰ类抗原的抗体可能通过细胞表面抗原的结合直接致敏/激活 PMN，并且抗原密度对 PMN 生理学的这些变化似乎很重要。
