Burlingham W J, Pan M H, Mason B, Ceman S, Sollinger H W
Department of Surgery, University of Wisconsin Hospital, Madison 53792.
Transplantation. 1988 Jun;45(6):1066-71. doi: 10.1097/00007890-198806000-00013.
A patient (HLA-A2,3; B35,60) with end-stage renal disease and a high level of pretransfusion (t0) anti-HLA cytotoxic antibodies (60% positive to a random panel), but lacking cytotoxic antibodies against her HLA haploidentical sister (HLA-A2,3; B35,44), received 3 donor-specific transfusions (DST) from the latter: 200 cc fresh whole blood at biweekly intervals, while being treated with azathioprine (AZA, 1 mg/kg/day). Her serum remained negative for antidonor antibodies both by standard cytotoxicity assay and by immunofluorescence flow cytometry after DST + AZA treatment, and she experienced no acute rejection episodes following donor kidney transplantation. Microcytotoxicity inhibition tests were performed using standard HLA-typing sera as a source of Ab-1, and pre- and posttransfusion sera were added to serial dilutions of Ab-1 to test for the presence of Ab-2 (antiidiotype) to donor HLA class I specificities. Although both pre- and posttransfusion sera inhibited cytotoxicity toward HLA-A2 antigens expressed on recipient target cells, only posttransfusion serum was found to inhibit cytotoxicity against the HLA-A2 antigens expressed on donor target cells. Absorption of soluble HLA class I antigens present in pre- or posttransfusion sera removed the inhibition of cytotoxicity toward recipient HLA-A2 but did not affect the inhibition of cytotoxicity toward donor HLA-A2 by posttransfusion sera. The F(ab')2 fragment of the IgG fraction of posttransfusion sera contained the inhibitory activity, suggesting induction of Ab-2 toward idiotypes specific for donor HLA-A2 antigens encoded on the unshared haplotype.
一名患有终末期肾病的患者（HLA-A2,3；B35,60），输血前（t0）抗HLA细胞毒性抗体水平较高（对随机细胞毒试验板60%呈阳性），但缺乏针对其HLA单倍型相同姐妹（HLA-A2,3；B35,44）的细胞毒性抗体，接受了来自后者的3次供者特异性输血（DST）：每两周输注200 cc新鲜全血，同时接受硫唑嘌呤（AZA，1 mg/kg/天）治疗。在DST + AZA治疗后，通过标准细胞毒性试验和免疫荧光流式细胞术检测，其血清中抗供者抗体均为阴性，并且在接受供者肾移植后未发生急性排斥反应。使用标准HLA分型血清作为Ab-1来源进行微量细胞毒性抑制试验，将输血前和输血后血清加入Ab-1的系列稀释液中，以检测是否存在针对供者HLA I类特异性的Ab-2（抗独特型）。尽管输血前和输血后血清均抑制了对受者靶细胞上表达的HLA-A2抗原的细胞毒性，但仅发现输血后血清抑制了对供者靶细胞上表达的HLA-A2抗原的细胞毒性。输血前或输血后血清中存在的可溶性HLA I类抗原的吸收消除了对受者HLA-A2细胞毒性的抑制，但不影响输血后血清对供者HLA-A2细胞毒性的抑制。输血后血清IgG组分的F(ab')2片段具有抑制活性，提示诱导产生了针对非共享单倍型上编码的供者HLA-A2抗原独特型的Ab-2。
