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目的 :进一步探索GVHD的发病机理 ,提高临床移植疗效。方法 :采用国际通用的微量淋巴细胞毒试验和混合淋巴细胞培养方法 ;基因分型采用PCR SSP方法 ,对基因亚型进行DNA测序 ,再进行HLA三维结构模拟。结果 :① 4名骨髓移植患者中 ,例 1供 受体间HLA Ⅰ、Ⅱ类血清学分型相合 ,DQB1基因亚型不同 ,例 2、3、4均有 1个Ⅰ类抗原 (分别为HLA A、B和A)血清学分型不合和 1个基因亚型不同。HLA三维结构模拟例 1、3、4供 受者差别明显 ,骨髓移植后发生了Ⅲ～Ⅳ度GVHD ;例 2三维结构模拟差别不明显 ,仅发生Ⅰ度GVHD ;② 4个病例供 受体间HLA分子分别相差 14、17、2 0、12个氨基酸 ,相差数量与GVHD无相关性 ;3例重度GVHD供 受体的HLA分子三维结构均在抗原结合区的β转角处出现明显差异 ,而 1例轻度GVHD则无明显差异。 结论 :当异基因骨髓移植供 受体间HLA基因亚型不同时 ,移植后发生GVHD的程度与HLA分子三维结构差别大小有密切关系 ;三维结构的差别又与差异氨基酸所处的位置有关 ;GVHD与抗原氨基酸差别的数量多少没有直接关系。
Objective: To further explore the pathogenesis of GVHD and improve the clinical efficacy of transplantation. Methods: The most commonly used method of microlymph lymphocytotoxicity and mixed lymphocyte culture were used. Genotyping PCR-SSP method was used to genotype the DNA sequence and HLA three-dimensional structure simulation. RESULTS: Among the 4 bone marrow transplant recipients, HLA class I and II serotypes were coincident with HLA class I and HLA class II subtypes in Example 1, and there were 1 class I antigens in cases 2, 3 and 4 (HLA A , B and A) serological typing is different from that of one gene subtype. HLA 3-D structural simulation of 1, 3, 4 for the recipient was significantly different, bone marrow transplantation occurred after Ⅲ ~ Ⅳ degree GVHD; Example 2 three-dimensional structure simulation was not obvious, only grade Ⅰ GVHD; ② 4 cases for the recipient HLA molecules were 14,17,2 0,12 amino acids difference, the number of differences and GVHD no correlation; three cases of severe GVHD donor HLA molecules three-dimensional structure of the antigen binding region of β-turn significant differences, and 1 Cases of mild GVHD no significant difference. CONCLUSION: When allogenic HLA genotypes are different between allogeneic bone marrow transplantation recipients, the degree of GVHD after transplantation is closely related to the difference in the three-dimensional structure of HLA molecules. The difference of three-dimensional structure is related to the location of different amino acids. GVHD There is no direct relationship between the number of amino acids and antigen number.