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Biomedical subjects

G G Persijn

Publications and source records attributed to G G Persijn.

At least 127 records · Page 7Linked to original sources

An eight-year study of HLA typing proficiency in Eurotransplant.

The main purpose of Eurotransplant, an international organ exchange organisation, is to maximize the survival time of transplanted organs through tissue typing and matching. Regular proficiency testings are necessary to assess the reproducibility and the reliability of the HLA typings performed by the individual typing centres. Two different protocols have been used: 1) since 1978, 35 samples of blood and donor spleen were used for cell exchanges (CE) and typed by all participating laboratories; 2) since 1977 samples of donor spleen have been shipped to the reference laboratory in Leiden for retyping (RD) resulting in over 2600 comparable HLA typings. The discrepancy rates of the HLA-A, B, C and DR specificities were analysed over the years. A large number of discrepancies was due to false negative assignments which led to assumed homozygosity at one or more HLA-loci. The recognition of HLA-DR has improved dramatically but with much variation per DR specificity. The concordancy rates for HLA-AB + DR have improved from 40% in 1981 to 91% for CE and 80% for RD typings in 1984. The reproducibility of DR typings in individual laboratories also has improved greatly but there is still considerable variation between the different laboratories.

Antigen-Presenting Cells↗

Eurotransplant. Part II. The cyclosporine era 1981-1985.

1. The realization of the two main goals of the Eurotransplant Organization have been enhanced during the period between 1981 and 1985 by two factors: A reliable HLA-A, -B and -DR typing of kidney donors and recipients, reflected in this analysis by the Hardy-Weinberg analysis but also by the results of the regular tissue typing quality controls. The number of patients who received a kidney without HLA-DR mismatches was 53% (N = 2,904). A significant difference with the 390 of 5,535 (7%) patients who received a kidney with two HLA-DR mismatches. 2. Treatment with cyclosporine increases kidney graft survival significantly in recipients of a first cadaveric transplant which is in agreement with the results of many other groups. Also a significant improvement in kidney graft survival with cyclosporine treatment was observed in recipients of a cadaveric retransplant, an observation in contrast with those of UCLA. 3. Although no significant influence of HLA-A and -B matching was observed in patients treated with or without cyclosporine, the best matched patients had the best graft survival. As stated many times before, the beneficial effect of HLA-A and -B matching is best demonstrated four or five years posttransplantation. 4. The effect of HLA-DR matching on kidney graft survival is highly significant, regardless of whether cyclosporine has been used or not. This finding is also in accordance with those of other investigators. 5. Prolonged cold ischemia periods in cyclosporine-treated patients resulted in a significant decrease of kidney graft survival. This is in contrast with the observations in non-cyclosporine-treated recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporins↗

Cyclosporin-A experience in Eurotransplant--preliminary data.

Since 1981, more and more transplant centres collaborating within the Eurotransplant Organization started to use Cyclosporin-A (CsA) as part of their immunosuppressive protocols. Although these protocols differ from centre to centre it was felt important to study the clinical significance of CsA on renal allograft survival, especially with regard to other relevant but more constant factors such as HLA-A, -B and -DR matching, pretransplant blood transfusions, ischemia times, etc. This study encompasses 3150 transfused kidney transplant recipients of whom 765 have received CsA. Analysis shows that the group of CsA treated patients had a significantly better graft survival as compared to the non-CsA treated patients i.e., 71% versus 62% at 2 years respectively. The best kidney graft survival was obtained in the HLA-DR well matched donor-recipients combinations even when CsA was used (79% at 2 years). A significant adverse effect of prolonged cold ischemia times was observed when CsA was administered.

Cyclosporins↗

The influence of warm and cold ischemic time on the outcome of cadaveric renal transplantation.

The influence of warm and cold ischemic time (WIT and CIT) on renal allograft function and allograft survival rates was analyzed from the Eurotransplant data. From 1977 through 1980 renal allograft recipients were divided into three groups, according to the length of the WIT of their graft: group I, 0-10 min (n = 2,636); group II, 11-20 min (n = 108); group III, 21-35 min (n = 17). Differences in graft function or graft survival have not been observed between these groups. It is concluded that donor kidneys with a WIT up to 20 min are acceptable for transplantation. The transplantation results in group III suggest that 35 min is a safe limit for acceptance, but the small number of transplantations in this group does not justify a firm conclusion. A combined analysis of warm and cold ischemia shows that simple cold storage up to 50 h is safe and acceptable, provided that warm ischemia is kept minimal (less than 10 min). It seems advisable to keep hypothermic preservation within the limit of 30 h, when WIT exceeds 10 min.

Cold Temperature↗

Excellent outcome after transplantation of renal allografts from HLA-DRw6-positive donors even in HLA-DR mismatches.

The effect of the presence or absence in the donor of HLA-DRw6 on the survival of renal allografts was studied in 759 HLA-DRw6-negative recipients. The definition of HLA-DRw6 was consistent throughout the study period. 578 patients received an allograft with one HLA-DR mismatch and 181 an allograft with two HLA-DR mismatches. Allograft survival at 1 year was significantly better when the donors were HLA-DRw6-positive than when they were HLA-DRw6-negative, for both one-DR-mismatched (86% vs 65%) and two-DR-mismatched (85% vs 59%) allografts.

Cytotoxicity Tests, Immunologic↗

HLA-DRw6 and renal allograft rejection.

HLA-DRw6-positive patients are "high responders" to certain renal allograft antigens. A study was therefore conducted of the outcome of 247 first renal allografts in 74 DRw6-positive and 173 DRw6-negative recipients. The effectiveness of matching for HLA-DR determinants in both groups was also analysed. The one-year graft survival in DRw6-positive patients was 59% as compared with 75% in DRw6-negative recipients (p = 0.012). A striking difference between the two groups was that HLA-DR matching significantly improved renal allograft survival only in the DRw6-positive patients. In those patients the one-year survival of HLA-DR-identical grafts was 95% as compared with only 38% for 2-DR mismatched grafts (p = 0.009). In DRw6-negative patients only a slight beneficial effect of HLA-DR matching was observed (83% versus 72% at one year for the 0-DR and 2-DR mismatched grafts, respectively) (p greater than 0.05). These findings are clear evidence that DRw6-positive patients (about a quarter of the patients on the waiting list of Eurotransplant) should be given HLA-DR-identical kidney transplants only.

Graft Rejection↗

Differential resistance to paralytic poliomyelitis controlled by histocompatibility leukocyte antigens.

To investigate whether genetic factors encoded by the histocompatibility leukocyte antigen (HLA) complex influence resistance to poliomyelitis, the pattern of inheritance of HLA haplotypes within affected families was studied. Seventeen informative families were available from a genetically homogeneous, unvaccinated community in The Netherlands after a single epidemic of poliomyelitis. Whereas none of 17 other polymorphic markers deviated from the expected Mendelian pattern of inheritance, the inheritance pattern of HLA haplotypes did. In sibpairs consisting of a patient with paralytic poliomyelitis and a nonparalytic control sib, significantly less sharing of HLA haplotypes was observed than would be expected by chance alone (P = 0.014). The sharing of HLA haplotypes between patients with nonparalytic poliomyelitis and healthy controls did not deviate significantly from the expected value. These data suggest that HLA-encoded genetic factors control resistance to the paralytic form of poliomyelitis.

Adolescent↗

Beneficial effect of HLA-A and B matched pretransplant blood transfusions on primary cadaveric kidney graft survival.

The effects of HLA-A and B matched pretransplant blood transfusions on the survival of a primary cadaveric kidney graft were studied prospectively in a group of 15 patients who had never received a transfusion and had never been pregnant. Kidney graft survival at one year was 87%, whereas a group of 14 nontransfused patients who underwent transplantation in the same center (before this study was initiated) had a graft survival of only 7%. Twenty-six patients who received a transplant in the same center just before and after each protocol patient served as controls. There were no prior pregnancies in this group; all patients had received blood transfusions from random blood bank donors. Kidney graft survival at one year was 76% for this control group, which is not statistically different from that found for the protocol group. Graft survival for the 13 contralateral kidneys from the protocol group donors was only 50% at one year. These kidneys, however, were transplanted in various other centers. From our study, prolongation of kidney graft survival could be demonstrated for patients receiving pretransplant HLA-A-and-B-matched blood transfusions. Sera screening indicated that lymphocytotoxicity might be reduced by pretransplant HLA-A-and-B-matched blood transfusions. The presence of pretransplant antibodies with specificities for HLA-A and/or B could be significantly correlated with poor graft survival.

Adolescent↗

Effect of warm ischemia time and HLA (A and B) matching on renal cadaveric graft survival and rejection episodes.

In a retrospective single-center study the influence of warm ischemia time and simultaneous influence of HLA (A and B) matching on one-year renal graft survival was analyzed in 170 adult recipients of primary cadaveric renal grafts. One-year survival of grafts with warm ischemia times longer than 50 min was only 40% (n = 10). When warm ischemia time was shorter than 50 min, a 1-min increase of warm ischemia time correlated with 1% decrease in one-year graft survival as a result of rejection. This detrimental effect of warm ischemia time on graft survival was not yet significant one month after transplantation, but became more evident as follow-up time was lengthened. Warm ischemia time also correlated with the number of reversible rejection episodes in patients with a graft functioning for longer than one year (P less than 0.04). The beneficial influence of HLA (A and B) matching on one-year graft survival was significant (P less than 0.05 log linear test). This influence was even more evident with longer warm ischemia times. It is concluded that warm ischemia has a detrimental influence on graft survival that is mediated by rejection, and it is suggested that this might be due in part to altered presentation or expression of HLA-antigens of ischemically damaged kidney tissues.

Adult↗

Transplant survival and clinical course after pretransplant HLA-A and B matched blood transfusions: a single centre study.

The effects of HLA-A and B matched pretransplant blood transfusions on the outcome of primary cadaveric kidney transplantation were studied prospectively in a group of 15 patients who had never received a transplant and had never been pregnant. From our study, prolongation of graft survival could be demonstrated for patients receiving pretransplant HLA-A and B matched blood transfusions. The clinical course was comparable to that found in a group of patients who received random pretransplant blood transfusions, although there were considerably more patients in this latter group hospitalised for a very long period, a fact which could be attributed mainly to viral infections.

Adolescent↗