Zoet Yvonne M, Eijsink Chantal, Kardol Marrie J, Franke-van Dijk Marry E I, Wilson G Louis, de Paus Roel, Mickelson Eric, Heemskerk Mirjam, van den Elsen Peter J, Claas Frans H J, Mulder Arend, Doxiadis Ilias I N
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Hum Immunol. 2005 May;66(5):519-25. doi: 10.1016/j.humimm.2005.01.007. Epub 2005 Feb 12.
Definition of the antibody specificity in the serum of patients waiting for a renal transplant or in need for platelet transfusion is a crucial step for finding adequate donors. Confounding factors are the complexity of the serum antibodies and the expression of several, up to six, different human leukocyte antigens (HLA) on peripheral blood lymphocytes used as target cells in the antibody screening. Single antigen-expressing (SAL) cell lines were generated by transfecting human major histocompatibility complex (MHC) class I sequences into K562, an erythroleukemia-derived cell line lacking MHC class I and II expression. Thirty-seven different SALs have been generated so far. In this study, we present the validation of 16 of those SALs by flow cytometry against a panel of 84 human HLA-specific monoclonal antibodies (30 HLA-A [8 IgG/22 IgM], 45 HLA-B [18 IgG/27 IgM], 6 HLA-A, B [3 IgG/3 IgM], and 3 HLA-C [all IgM]) developed in our laboratory. The SALs proved to be suitable tools to determine acceptable mismatches for highly sensitized patients. This concept of transfecting target sequences in immortalized cell lines opens up new avenues in the definition of serum and cellular reactivity for sensitized patients awaiting a suitable organ or blood component.
确定等待肾移植或需要血小板输注患者血清中的抗体特异性是找到合适供体的关键步骤。混杂因素包括血清抗体的复杂性以及用作抗体筛查靶细胞的外周血淋巴细胞上多达六种不同人类白细胞抗原(HLA)的表达。通过将人类主要组织相容性复合体(MHC)I类序列转染到缺乏MHC I类和II类表达的红白血病衍生细胞系K562中,产生了单抗原表达(SAL)细胞系。到目前为止,已经产生了37种不同的SAL。在本研究中,我们通过流式细胞术对16种此类SAL进行了验证,所用对照为我们实验室开发的一组84种人类HLA特异性单克隆抗体(30种HLA - A [8种IgG/22种IgM],45种HLA - B [18种IgG/27种IgM],6种HLA - A、B [3种IgG/3种IgM],以及3种HLA - C [均为IgM])。这些SAL被证明是确定高度致敏患者可接受错配的合适工具。在永生化细胞系中转染靶序列这一概念为定义等待合适器官或血液成分的致敏患者的血清和细胞反应性开辟了新途径。