CAJ | 학술논문

目的研究HLA-Cw位点低分辨基因分型"纯合子"的等位基因特性,为临床移植配型提供精确资料.方法在43例血缘关系造血干细胞移植(HSCT)供受者中,对中国最常见的低分辨基因分型Cw*03和Cw*07的"纯合子"个体采用聚合酶链反应-序列特异性引物(PCR-SSP)高分辨基因分型方法进行等位基因定型,并采用自主研制的三维结构匹配软件系统(HLA StrucMark version1.0)对其等位基因产物进行三维结构匹配,以预测不同分辨率分型结果对移植物抗宿主病(GVHD)发生的影响.结果低分辨基因分型Cw*03、Cw*07"纯合子"个体的高分辨基因分型结果显示Cw*03及Cw*07的纯合子分别为14%和43%,其余均为Cw*03及Cw*07杂合子个体.可见其低分辨基因分型易造成供受者问等位基因的错配;在有家系校正的情况下,标本的低分辨模糊结果可以通过家系遗传分析来校正定型;在无家系校正的情况下,应通过高分辨基因分型来确定等位基因,三维结构差异分析则显示这些错配有可能造成HSCT后GVHD的发生.结论当低分辨基因分型结果只出现Cw位点"纯合子"时,有家系的标本应当以家系分型结果校正定型,无家系校正的标本应当用高分辨基因分型方法进行核实,从而为临床移植提供准确的配型报告,以防止无关供-受者HSCT后因等位基因错配而引起的严重GVHD.
목적 연구HLA-Cw위점저분변기인분형"순합자"적등위기인특성,위림상이식배형제공정학자료.방법 재43례혈연관계조혈간세포이식(HSCT)공수자중,대중국최상견적저분변기인분형Cw*03화Cw*07적"순합자"개체채용취합매련반응-서렬특이성인물(PCR-SSP)고분변기인분형방법 진행등위기인정형,병채용자주연제적삼유결구필배연건계통(HLA StrucMark version1.0)대기등위기인산물진행삼유결구필배,이예측불동분변솔분형결과 대이식물항숙주병(GVHD)발생적영향.결과 저분변기인분형Cw*03、Cw*07"순합자"개체적고분변기인분형결과 현시Cw*03급Cw*07적순합자분별위14%화43%,기여균위Cw*03급Cw*07잡합자개체.가견기저분변기인분형역조성공수자문등위기인적착배;재유가계교정적정황하,표본적저분변모호결과 가이통과가계유전분석래교정정형;재무가계교정적정황하,응통과고분변기인분형래학정등위기인,삼유결구차이분석칙현시저사착배유가능조성HSCT후GVHD적발생.결론 당저분변기인분형결과 지출현Cw위점"순합자"시,유가계적표본응당이가계분형결과 교정정형,무가계교정적표본응당용고분변기인분형방법 진행핵실,종이위림상이식제공준학적배형보고,이방지무관공-수자HSCT후인등위기인착배이인기적엄중GVHD.
Objective To study the allelic characteristics of "homozygote" resulted from low resolution genotyping of HLA-Cw locus and to provide more precise typing data for clinical transplantation. Methods Forty three related allogeneic hematopoietic stem cell transplantation(allo-HSCT) donors and patients with HLA-Cw * 03, Cw * 07 homozygote, which were the most common gene groups in Chinese population, identified by low resolution genotyping level were retyped by high resolution PCR-SSP genotyping method, and three dimensional structure modelling was also made by using a solely developed HLA three-dimensional matching software (HLA strucMark version 1.0) to evaluate the effect of differences between two mismatched alleles and its relationship with GVHD occurrence. Results The typing results of high resolution level demonstrated that the confirmed allelic homozygotes for Cw *03 and Cw *07 were 14% and 43%, respectively, while the others were all heterozygotes. The ambiguous typing results could be confirmed by family data study or by high resolution typing methods when there was no family data available, Three-dimensional modeling results of the mismatched alleles undetected in low resolution typing level indicated that family data study or high resolution PCR-SSP genotyping were important in preventing graft-versus-host disease. Conclusions When HLA-Cw ho-mozygote results were found in low resolution genotyping method, the results should be reconfirmed by family data study or by high resolution typing methods to provide precise typing results for avoiding severe graft-ver-sus-host disease.