CD31 mismatching affects marrow transplantation outcome
CD31 mismatching affects marrow transplantation outcome
复制标题
DOI：
10.1053/bbmt.2001.v7.pm11669217
复制
发表时间：
2001-01-01
影响因子：
4.3
通讯作者：
Negrin, RS
中科院分区：
文献类型：
--
作者：
Grumet, FC;Hiraki, DD;Negrin, RS
与同种异体骨髓移植 (BMT) 并发的移植物抗宿主病 (GVHD) 通常归因于次要组织相容性抗原 (mHags) 不匹配，而这种抗原在人类中的定义尚不清楚。 CD31 是与急性 GVHD 相关的候选人类 mHag，但报告对其重要性水平、HLA 限制的作用以及分子内不同多态性密码子的相对重要性存在不同意见。因此，我们在单个机构的一项前瞻性研究中更详细地研究了 CD31 匹配对 BMT 结果的影响。移植前收集受体和供体 DNA 样本。适用于在我们机构 45 个月内接受来自 FILA 相同兄弟姐妹的未操作骨髓的所有患者。对 118 个患者-供体对以及另外 2 对仅进行密码子 125 分型的患者-供体对进行了 3 个多态性密码子 125（L 或 V）、563（N 或 S）和 670（R 或 G）等位基因的 CD31 DNA 分型。测试供体-受体 CD31 不一致与严重急性 GVHD、慢性 GVHD、复发和生存的 BMT 临床结果指标的相关性。所有 3 个密码子的每个等位基因的基因频率约为 0.5，与之前的报告相当。由于发现 563N 与 670G 以及 563S 与 670R 完全关联，因此这些密码子的非同一性被分析为指定为密码子 563/670 的单一遗传标记。供体-受体 CD31 不一致是总体生存的重要危险因素，无论是在密码子 563/670（风险比 [hr] = 2.58，P = .005）还是在密码子 125（hr = 1.07，P = .036）。对于无病生存也有类似的结果。密码子 563/670 的不一致也是重度（III 级、IV 级）与无（0 级）急性 GVHD 的显着风险因素（比值比 [OR] = 11.15，P = .011）。密码子 125 的不一致带来的风险较小，但仍然显着（OR = 9.30，P = .030）。当没有严重急性 GVHD 的对照组扩大到包括 I 级和 0 级患者时，密码子 563/670（OR = 12.31，P = .010）和密码子 125（OR = 11.24，P = .011）的 CD31 不一致的风险均增加。当对成年期、受者-供者性别差异、种族、疾病、移植前风险类别、HLA-A2 类型、B44 样类型和 GVHD 预防方案等协变量进行多变量分析时，CD31 不一致仍然是生存和严重急性 GVHD 的重要独立危险因素。 CD31 不一致显示出趋势，但作为复发和慢性 GVHD 的危险因素未能达到统计学意义。总之，供体-受体 CD31 不一致是 BLA 相同同胞 BMT 中生存和严重急性 GVHD 的重要危险因素。与密码子 563/670 更强的关联表明多态性可能比密码子 125 处的相关多态性更重要。
Graft-versus-host disease (GVHD) complicating allogeneic bone marrow transplantation (BMT) is often attributed to mismatched minor histocompatibility antigens (mHags), which are poorly defined in humans. CD31 is a candidate human mHag relevant to acute GVHD, but reports disagree about its level of significance, the role of HLA restriction, and the relative importance of different polymorphic codons within the molecule. We therefore examined in greater detail the impact of CD31-matching on BMT outcome in a prospective study from a single institution. Samples of recipient and donor DNA were collected pretransplantation. for all patients receiving unmanipulated bone marrow from an FILA-identical sibling over a 45-month period at our institution. CD31 DNA typing of alleles at the 3 polymorphic codons 125 (L or V), 563 (N or S), and 670 (R or G) was performed for 118 patient-donor pairs plus 2 additional pairs who had codon 125 typing only. Donor-recipient CD31 nonidentity was tested for correlation with BMT clinical outcome measures of severe acute GVHD, chronic GVHD, relapse, and survival. Gene frequencies of approximately 0.5 for each allele at all 3 codons were comparable to previous reports. Because complete association was seen for 563N with 670G and for 563S with 670R, nonidentity for those codons was analyzed as a single genetic marker designated codon 563/670. Donor-recipient CD31 nonidentity was a significant risk factor for overall survival, both at codon 563/670 (hazard ratio [hr] = 2.58, P = .005) and at codon 125 (hr = 1.07, P = .036). Similar results held for disease-free survival. Nonidentity at codon 563/670 was also a significant risk factor (odds ratio [OR] = 11.15, P = .011) for severe (grades III, IV) versus no (grade 0) acute GVHD. Nonidentity at codon 125 posed less but still significant risk (OR = 9.30, P = .030). When the comparison group without severe acute GVHD was expanded to include grade I as well as grade 0 patients, the risk from CD31 nonidentity increased for both, codon 563/670 (OR = 12.31, P = .010) and codon 125 (OR = 11.24, P = .011). CD31 nonidentity remained a significant independent risk factor for survival and for severe acute GVHD when tested in multivariate analysis with the covariates of adulthood, recipient-donor sex difference, ethnic group, disease, pretransplantation risk category, HLA-A2 type, B44-like types, and GVHD prophylactic regimen. CD31 nonidentity showed a trend but failed to achieve statistical significance as a risk factor for relapse and for chronic GVHD. In conclusion, donor-recipient CD31 nonidentity is a significant risk factor for survival and for severe acute GVHD in BLA-identical sibling BMT. The stronger associations with codon 563/670 suggest that polymorphism may be more important than the linked polymorphism at codon 125.