Correlation Between MHC Class I-related Chain A Gene Alleles And Posttransplant Rejective Reaction In Small Intestine, Liver And Kidney

This study was undertaken with the primary aim of analyzing the clinical relevance of major histocompatibility complex (MHC) class I chain-related gene A (MICA) alleles and posttransplant rejective reaction in live related donor (LRD) small intestine, liver and kidney transplantation. Genome DNA were extracted from blood preparation or pathological sections which were collected from donors and recipients of living-related transplantion including 4 cases small bowel transplantation, 5 cases of liver transplantion and 6 cases of kidney transplantion. HLA Zygosity of all cases of transplantation were confirmed to be half-matching. Eight frequent MICA generic types (MICA*008, MICA*010, MICA*002, MICA*012, MICA*007, MICA*004, MICA*017 and MICA*049) consisit of 13 alleles were choosed and detected by way of sequence-specific primers (PCR-SSP). It has been reported that patients with lower matching rate of HLA have more acute rejection episodes as compared with the higher matching rate ones and also have poor graft survival. Similarly, we found that patients with lower matching rate of MICA alleles also had more severe clinical and pathological rejection and shorter graft survival as compared with the higher matching rate ones(P<0.05). This study illustrated that there was some kind of correlation between matching rate of MICA alleles and posttransplant acute rejective reaction or survival time. MICA could be an important prognostic marker in live related donor organ transplantation.METHODS:1. Extracted blood preparation or pathological sections which were collected from donors and recipients of living-related transplantion including 4 cases small bowel transplantation (1999-2003), 5 cases of liver transplantion (2006-2008) and 6 cases of kidney transplantion (2006-2008).2. DNA of all cases was extracted from whole blood or pathological sections using HLA-Morgantm ABDR SSP Kit (Texas BioGene,Inc) according to the manufacturers'instructions, HLA typing were performed by DNA sequencing, including all alleles of HLA-A, HLA-B, HLA-DR.3. We chosed 8 frequent MICA generic types consisting of 13 alleles in Chinese (MICA*008, MICA*010, MICA*002, MICA*012, MICA*007, MICA*004, MICA*017, MICA*049). MICA alleles were determinated by polymerase chain reaction based on sequence-specific primers(PCR-SSP).4. The correlation between matching rate of 13 alleles of MICA and levels of posttransplant acute rejective reaction in donors and recipients were analyzed by using statistical Analysis. RESULTS:1. Fifteen donor–recipient pairs were all HLA half-matching whose relationship were parents and children except for one case of uncle and nephew in LRD kidney transplantation.2. Under the same benchmark of HLA matching, we found that MICA matching of three kinds of LDR organ transplantations was irregular. The highest MICA matching rate in LRD small intestine transplantation was 10/13, the lowest one was 4/13. Table 3 shows the MICA alleles matching rate between donors and recipients in three kinds of LRD organ transplantations.3. We had observed negative correlation between MICA matching rate and pathological classification (coefficient correlation= -0.667, P<0.05). That is, The recipients displaying higher matching rates of MICA alleles with donors showed lighter clinical and pathological rejection and longer survival time. Table 3 shows the survival of total 15 recipients until the testing completed. We can found the tendency that recipient who had higher MICA matching rate had showed longer survival time (coefficient of regression= -0.795, RR= 0.451, 95% confidence interval= 0.212-0.962). That is to say, matching rate of MICA is the protection factor to survival.4.. Taking 6.5/13 as standard, we divided all cases into two groups and contrasted the disparity between them by Log Rank (coefficient correlation= 4.967, P<0.05). Statistic hint that there is disparity between two groups (>6/13 and <=6/13). Figure 14 shows the survival curve of each group.CONCLUSION:Our data indicates some kind of tendency that matching rates of MICA alleles bwtween recipients and donors have negtive relevance to acute rejective reaction, and positive relevance to survival time of recipient after small bowel, liver, and kidney transplantation. There will be more MICA antibody produced and more severe postgraft rejection when MICA matching rate is lower. On the contrary, there will be fewer MICA antibody produced when MICA matching rate is higher. According to our research, non-classical HLA antigen plays the important roles when HLA matching rate is same. So we should carry out MICA matching between recipients and donors before LRD organ transplantation probably.