Mueller Regula J, Stussi Georg, Odermatt Bernhard, Halter Jörg, Schanz Urs, Seebach Jörg D
Laboratory for Transplantation Immunology, Department of Internal Medicine, Univeristy Hospital Zürich, Zürich, Switzerland.
Xenotransplantation. 2006 Mar;13(2):126-32. doi: 10.1111/j.1399-3089.2006.00281.x.
In contrast to human leukocyte antigen (HLA) matching, ABO-blood group incompatibility plays a minor role in the success of allogeneic hematopoietic stem cell transplantation (HSCT). Incompatible ABH histo-blood group antigens, expressed on recipient endothelial cells (EC) and donor erythroid progenitor cells, may represent targets for graft-versus-host disease (GVHD) and host-versus-graft reactions, respectively. The aims of the current study were to investigate: (1) red blood cell (RBC) engraftment and (2) EC chimerism as a potential result of replacement of recipient EC by donor bone marrow (BM)-derived EC in a patient following major ABO-incompatible (A to O) and gender-mismatched HSCT, who died at day 350 of severe acute GVHD.
Blood counts and anti-A/B isoagglutinin titers were analyzed repeatedly. Heart and BM specimens were obtained at autopsy. The expression of ABH histo-blood group antigens was examined by immunhistochemistry, X/Y chromosomes were detected by chromogen in situ hybridization (CISH).
RBC engraftment defined as appearance of 1% reticulocytes in the peripheral blood was delayed and correlated with anti-donor isoagglutinin titers. Circulating hematopoietic cells were exclusively of donor origin demonstrating full donor hematopoietic chimerism, whereas EC in heart and BM blood vessels were exclusively of the recipient type.
Pure red cell aplasia (PRCA) after major ABO-incompatible HSCT was caused by anti-A/B isoagglutinins produced by recipient-type plasma cells. Using ABO and gender mismatch for discrimination, heart and BM blood vessels demonstrated no evidence for EC chimerism 11 months after ABO-incompatible HSCT. These findings suggest that EC replacement and chimerism do not represent major mechanisms responsible for tolerance induction after HSCT.
与人类白细胞抗原（HLA）配型不同，ABO血型不相容在异基因造血干细胞移植（HSCT）成功中所起作用较小。受体内皮细胞（EC）和供体红系祖细胞上表达的不相容ABH组织血型抗原，可能分别是移植物抗宿主病（GVHD）和宿主抗移植物反应的靶点。本研究的目的是调查：（1）红细胞（RBC）植入情况，以及（2）在一名主要ABO不相容（A到O）且性别不匹配的HSCT患者中，供体骨髓（BM）来源的EC替代受体EC后，作为潜在结果的EC嵌合情况。该患者在严重急性GVHD的第350天死亡。
反复分析血细胞计数和抗A/B同种凝集素滴度。尸检时获取心脏和骨髓标本。通过免疫组织化学检查ABH组织血型抗原的表达，通过显色原位杂交（CISH）检测X/Y染色体。
定义为外周血中出现1%网织红细胞的RBC植入延迟，且与抗供体同种凝集素滴度相关。循环造血细胞完全来自供体，表明完全供体造血嵌合，而心脏和骨髓血管中的EC完全是受体类型。
主要ABO不相容HSCT后的纯红细胞再生障碍（PRCA）是由受体型浆细胞产生的抗A/B同种凝集素引起的。利用ABO和性别不匹配进行区分，在ABO不相容HSCT后11个月，心脏和骨髓血管未显示EC嵌合的证据。这些发现表明，EC替代和嵌合并非HSCT后耐受诱导的主要机制。
