Kögler Gesine, Middleton Peter G, Wilke Martina, Rocha Vanderson, Esendam Bennie, Enczmann Jürgen, Wernet Peter, Gluckman Eliane, Querol Sergio, Lecchi Lucilla, Goulmy Els, Dickinson Anne M
José Carreras Eurocord/Netcord Bank Germany, Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University, Moorenstrasse 5, Bldg. 14.80, 40225 Düsseldorf, Germany.
Transplantation. 2002 Oct 27;74(8):1167-75. doi: 10.1097/00007890-200210270-00019.
In HLA-identical sibling bone marrow transplantation, certain recipient cytokine gene polymorphism genotypes and minor histocompatibility differences influence the occurrence and severity of acute graft-versus-host disease (aGvHD). The present study investigated the role of cytokine tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 gene polymorphisms HY, HA-1, and CD31 minor histocompatibility antigen (mHag) mismatch in the development of aGvHD after unrelated cord blood (CB) transplant (CBT).
DNA samples of 115 CB recipients and their unrelated CB grafts were analyzed for genotype associated with TNF-alpha (TNFd3/d3) and IL-10 (IL-10(-1064), 11-16) and for disparities in major and three minor histocompatibility antigens, HY, HA-1, and CD31 codon 125. Results were correlated with the incidence of aGvHD grades II to IV.
Neither the donor nor the recipient GvHD risk alleles TNFd3/d3 and IL-10(-1064) (11-16) were associated with the development of aGvHD grades II to IV and I to IV. Because of the heterogeneity of CBTs, the data were reanalyzed separately for patients with malignancies (n=83) or with inborn errors (n=24). No significant association was observed between the severity of aGvHD and the possession of either TNFd3/d3 or IL-10 (11-16) genotypes. Mismatches for the mHags HY, HA-1, and CD31 exon 125 between donor and recipient did not associate with aGvHD grades II to IV.
In contrast to HLA-identical sibling bone marrow transplantation, in mismatched unrelated CBT, neither the cytokine genotypes TNFd3/d3 alone or in combination with IL-10(-1064) alleles nor the minor histocompatibility antigens HY, HA-1, and CD31 exon 125 were associated with aGvHD grades II to IV. Further determination of the cytokine gene polymorphism genotypes in CBTs compared with bone marrow transplants may identify those polymorphisms that could be potential predictive markers for the occurrence of aGvHD.
在人类白细胞抗原（HLA）匹配的同胞骨髓移植中，某些受者细胞因子基因多态性基因型和次要组织相容性差异会影响急性移植物抗宿主病（aGvHD）的发生和严重程度。本研究调查了细胞因子肿瘤坏死因子（TNF）-α和白细胞介素（IL）-10基因多态性HY、HA-1以及CD31次要组织相容性抗原（mHag）错配在非亲缘脐血（CB）移植（CBT）后aGvHD发生中的作用。
对115例CB受者及其非亲缘CB移植物的DNA样本进行分析，检测与TNF-α（TNFd3/d3）和IL-10（IL-10(-1064)，11-16）相关的基因型，以及主要和三种次要组织相容性抗原HY、HA-1和CD31密码子125的差异。结果与II至IV级aGvHD的发生率相关。
供者和受者的GvHD风险等位基因TNFd3/d3和IL-10(-1064)（11-16）均与II至IV级和I至IV级aGvHD的发生无关。由于CBT的异质性，分别对患有恶性肿瘤（n=83）或先天性疾病（n=24）的患者重新分析数据。未观察到aGvHD的严重程度与TNFd3/d3或IL-10（11-16）基因型的拥有情况之间存在显著关联。供者和受者之间mHags HY、HA-1和CD31外显子125的错配与II至IV级aGvHD无关。
与HLA匹配的同胞骨髓移植不同，在错配的非亲缘CBT中，单独的细胞因子基因型TNFd3/d3或与IL-10(-1064)等位基因组合，以及次要组织相容性抗原HY、HA-1和CD31外显子125均与II至IV级aGvHD无关。与骨髓移植相比，进一步确定CBT中的细胞因子基因多态性基因型可能会识别出那些可能成为aGvHD发生的潜在预测标志物的多态性。
