造血干细胞移植的HLA配型.ppt

造血干细胞移植的HLA配型 中国医学科学院血液病医院 杨栋林 HLA HLA (human leucocyte antigen) system or MHC (major histocompatibility complex) is the name given to the highly polymorphic gene cluster region on chromosome 6 which codes for cell surface proteins involved in immune recognition. 　HLA ,即人类主要组织相容性复合物(major histocompatibility complex , MHC) ,定位于人类6 号染色体短臂区域 6p21. 3 ,包括220 多个基因, 大小4Mb 左右。 其中许多基因编码免疫系统蛋白质,包括那些控制T 淋巴细胞和自然杀伤细胞反应的蛋白质。 The gene complex is subdivided into 2 regions Class 1 The A, B and C loci. These proteins are found on most nucleated cells and interact with CD8+ T lymphocytes. Class 2 Comprising of DR, DP, DQ loci present only on APC, such as B lymphocytes, monocytes, dendritic cells, macrophages and activated T lymphocytes. Interact with CD4+ T lymphocytes. HLA Proteins Expressed on Cells MHC-Ⅰ CD8+ T cells CTL MHC-Ⅱ CD4+ T cells Th cell 不发生重组时，子代间两条染色体相同的占25％，一条染色体相同的占50％，两条染色体都不相同的占25％。 理论上有1/4的患者可找到供者。 而寻找到配型完全相合的无关供者的概率只有1/10万。 Serologic Types (Antigen Names) Allele (DNA) Names Impact of Mismatch on Survival Allele vs. Antigen Mismatch: Survival DQ/DP: Survival DQ/DP Mismatching Is Not a Risk Factor Overall Survival by Matching Groups Matching Group N Survival Matched at 8 loci [16/16] 108 39% ± 9% MM at DQ/DP only 683 39% ± 4% Allele MM at A,B,C or DR 631 29% ± 4% Serologic MM 452 23% ± 4% * HLA-A, -B, -C, DRB1, DQA1, DQB1, DPA1 and DPB1 HLA-A, -B -DR Serologically Matched Pairsnumber of allele mismatches HLA-A, -B, -C -DR How many loci should we type? How many loci should I match? The Minimum Acceptable Matchin the NMDP How do we search for the best donor? Strategy: Search for an allele matched donor at HLA-A, -B, -C and DRB1 (8 of 8 allele match) Minimize the number of allele-level mismatches Try to avoid an antigen-level mismatch What if there is no perfect match? Assume that HLA-A, -B, -C and -DRB1 are equally important Accept one allele mismatch over one antigen mismatch Minimize the number of allele mismatches