| Co-Investigator(Kenkyū-buntansha) |
ICHIKAWA Yasuji HYOGO PREFECTURAL NISHINOMIYA HOSPITAL,DEPARTMENT OF UROLOGY AND RENAL TRANSPLAN, 腎移植センター, 部長
IHARA Hideari HYOGO COLLEGE OF MEDICINE,DEPARTMENT OF UROLOGY,ASSOCIATED PROFESSOR, 医学部, 講師 (30127188)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
The object of the present study was to confirm the HLA-DRB1 matching effect on rejection crisis, its severity and kidney graft survival based on genotyping and mixed lymphocyte reaction. Ninety-four renal allografts were included in this study. DNA typing of HLA-DRB1 was performed by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) method. The incidence of acute rejection within 6 months following transplantation, the frequency of OKT3 administration for steroid-resistant rejection, histopathological findings and graft survival rate were compared between the DRB1-matched (n=23) and DRB1-mismatched (n=71) groups. Four acute rejections occurred in the DRB1-matched group (incidence ; 17%) and 40 in the DRB1-mismatched group (56%). In the DRB1-mismatched group, the incidence of acute rejection was significantly less frequent than that of the DRB1-mismatched group (P<0.005). In the DRB1-matched group, only one patient received OKT3 administration (4%), in contrast to 16
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of 71 patients in the DRB1-mismatched group (23%). The use of OKT3 was significantly less frequent in the DRB1-matched group (P<0.05). Histopathological findings from biopsy specimens showed no constant distribution of pathological grade of acute rejection according to DRB1 matching in the present study. Graft survival rate in two groups did not differ significantly, but the graft survival rate in the DRB1-mismatched group had a tendency to decrease as the grafts survived longer.
Twenty-five HLA-DR matched living related transplants were included in mixed lymphocyte reaction test. These recipients and donors were genotyped and their class II alleles ; HLA-DRB1, -DQA,-DQB,-DPB,were examined. A stimulation index under 1.8 was defined as MLR compatible, because it was 1.15(]SY.+-[)0.58 (mean(]SY.+-[)2SD) in HLA-identical siblings. The graft survival rate at 2-year was 100% in the MLR-compatible transplants, while was 78% in the MLR-incompatible cases. Although there was no significant difference between two groups, the graft survival rate in the MLR-compatible transplants was relatively higher than in the MLR-incompatible cases. These results suggests that stimulation index has association with the graft outcome.
The DR-matched transplant were divided into 11 HLA-DRB1 matched and 14DRB1-mismatched cases. Mean stimulation index was 2.91 in the DRB1-matched cases and was 8.21 in the DRB1-mismatched cases. The stimulation index in DRB1-matched cases was lower than in the DRB1-mismatched cases. On the other han, the stimulation index was not significantly influenced by DQA matching, DQB matching and DPB matching. These result supported that HLA-DRB1 as the DR antigen in the molecular level had strongest effect on the MLR induction.
In conclusion, the results of the present study confirm that HLA-DRB1 matching has marked beneficial effects on kidney transplants through the weak stimulation of HLA antigen to the lymphocytes and, in the clinical transplants, reduction of the acute rejection rate and decrease of the severity of rejection and suggest that improvement of graft survival will be obtained through kidney allocation to a DRB1-matched recipient. Less
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