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用于选择非血缘关系骨髓供者的HLA基因分子分析

Molecular analysis of HLA genes for the selection of unrelated bone marrow donor.

作者信息

Mantovani V, Martinelli G, Bragliani M, Buzzi M, Selva P, Collina E, Farabegoli P, Rosti G A, Bandini G, Tura S

机构信息

Tissue Typing Laboratory, Malpighi Hospital, Bologna, Italy.

出版信息

Bone Marrow Transplant. 1995 Sep;16(3):329-35.

PMID:8535303
Abstract

The selection of fully matched unrelated volunteer donors (UVD) in BMT requires a molecular characterization of MHC polymorphism, since most phenotypically HLA-identical donors can be non-identical when analyzed at a genomic level. The present report describes a molecular typing protocol for HLA genes developed for the selection of UVD, and its application to some donor-recipient pairs. The protocol involves three successive steps. Firstly, PCR with sequence-specific primers for HLA-DRB1 and -DQB1 genes is performed to identify the major alleles of the recipient. PCR-fingerprint matching is then introduced for HLA-A, B, C and DRB, DQB and DPB genes to screen prospective donors. Those showing matched fingerprinting patterns are finally submitted to direct sequencing of the DRB1 gene. DPB compatibility is assessed by oligotyping when there are several potential class I and DRB matched donors. This strategy was applied retrospectively to three BMT recipients and their previously selected donors. Three other patients and their 12 prospective donors were submitted to our protocol before BMT. Clinical evaluation of transplant outcomes indicates the primary importance of complete DRB and class I matching, while DQB and DPB compatibility seems to be less critical.

摘要

在骨髓移植中选择完全匹配的无关志愿供者(UVD)需要对MHC多态性进行分子特征分析,因为大多数表型上HLA相同的供者在基因组水平分析时可能并不相同。本报告描述了一种为选择UVD而开发的HLA基因分子分型方案及其在一些供者 - 受者配对中的应用。该方案包括三个连续步骤。首先,使用针对HLA - DRB1和 - DQB1基因的序列特异性引物进行PCR,以鉴定受者的主要等位基因。然后对HLA - A、B、C和DRB、DQB及DPB基因引入PCR指纹匹配以筛选潜在供者。那些显示指纹匹配模式的供者最终进行DRB1基因的直接测序。当有几个潜在的I类和DRB匹配供者时,通过寡核苷酸分型评估DPB相容性。该策略被回顾性地应用于三名骨髓移植受者及其先前选择的供者。另外三名患者及其12名潜在供者在骨髓移植前接受了我们的方案。移植结果的临床评估表明完全的DRB和I类匹配至关重要,而DQB和DPB相容性似乎不太关键。

相似文献

1
Molecular analysis of HLA genes for the selection of unrelated bone marrow donor.用于选择非血缘关系骨髓供者的HLA基因分子分析
Bone Marrow Transplant. 1995 Sep;16(3):329-35.
2
New strategies for selection of unrelated bone marrow donors.选择非亲属骨髓供者的新策略。
Bone Marrow Transplant. 1993;11 Suppl 1:31-2.
3
Identification of unrelated HLA-identical bone marrow donors: RFLP, oligotyping and PCR fingerprinting for HLA class II compared to MLC responses.无关的HLA匹配骨髓供者的鉴定:与混合淋巴细胞培养反应相比,HLAⅡ类的限制性片段长度多态性分析、寡核苷酸分型及PCR指纹分析
Bone Marrow Transplant. 1993;11 Suppl 1:24-7.
4
MHC class III polymorphisms in selection of donors for BMT.骨髓移植供体选择中的MHC Ⅲ类多态性
Bone Marrow Transplant. 1993 Jan;11(1):37-41.
5
European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.欧洲无关供者匹配的骨髓移植治疗慢性粒细胞白血病的结果。HLA Ⅱ类匹配的影响。欧洲血液与骨髓移植组慢性白血病工作组
Bone Marrow Transplant. 1997 Jul;20(1):11-9. doi: 10.1038/sj.bmt.1700844.
6
Molecular techniques for typing unrelated marrow donors: potential impact of molecular typing disparity on donor selection.用于对非亲属骨髓供者进行分型的分子技术:分子分型差异对供者选择的潜在影响。
Bone Marrow Transplant. 1994;14 Suppl 4:S42-50.
7
Problems and possible solutions in finding an unrelated bone marrow donor. Results of consecutive searches for 240 Dutch patients.寻找非亲属骨髓供者的问题及可能的解决方法。240例荷兰患者连续搜索的结果。
Bone Marrow Transplant. 1997 Dec;20(12):1011-7. doi: 10.1038/sj.bmt.1701025.
8
Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/Cw/DRB1/B3/B5/DQB1-matched donor?非亲缘供者骨髓移植:找到一位HLA-A/B/Cw/DRB1/B3/B5/DQB1配型相合供者的概率是多少?
Bone Marrow Transplant. 2000 Aug;26(4):437-41. doi: 10.1038/sj.bmt.1702529.
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Selection of unrelated bone marrow donors: does the current procedure warrant complete MHC class II identity?无关骨髓供体的选择:当前程序是否需要完全的MHC II类匹配?
Beitr Infusionsther. 1992;30:320-3.
10
The extent of HLA class II allele level disparity in unrelated bone marrow transplantation: analysis of 1259 National Marrow Donor Program donor-recipient pairs.非亲缘骨髓移植中HLA II类等位基因水平的差异程度:对1259例国家骨髓捐献计划供受者配对的分析
Bone Marrow Transplant. 2000 Feb;25(4):385-93. doi: 10.1038/sj.bmt.1702161.

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Dig Dis Sci. 2007 Jan;52(1):179-84. doi: 10.1007/s10620-006-9495-4. Epub 2006 Dec 8.
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World J Gastroenterol. 2005 Mar 28;11(12):1862-6. doi: 10.3748/wjg.v11.i12.1862.
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HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity.
意大利北部与风湿性多肌痛相关的HLA - DRB1等位基因:与疾病严重程度的相关性
Ann Rheum Dis. 1999 May;58(5):303-8. doi: 10.1136/ard.58.5.303.