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J J van Rood

Publications and source records attributed to J J van Rood.

At least 19 recordsLinked to original sources
PubMed2000

The importance of H2 haplotype sharing in the induction of specific unresponsiveness by pretransplant blood transfusions.

BACKGROUND: The beneficial effect on graft survival achieved by pretransplant blood transfusions is well established. Previous studies have shown that the degree of major histocompatibility complex (MHC) (mis)-match between the transfusion donor and the recipient plays a determining role. However, other factors are also involved. In this study, we explored the hypothesis that, in addition to sharing of MHC antigens between the transfusion donor and the recipient, the MHC type of the organ donor is also of importance. METHODS: To mimic the human situation, F1 mice, rather than inbred strains, were pretreated with haplotype-shared allogeneic whole blood transfusions and transplanted with hearts of organ donors with different matched or mismatched H2 haplotypes. RESULTS: When a heart was transplanted 1 week after donor-specific transfusion (DST; blood transfusion donor=organ donor), an excellent prolongation of graft survival was obtained (median survival time: 77 days vs. 9 days in untreated mice). However, this was only the case when a haplotype was shared with the recipient; a DST given with no match between organ donor (=BT donor) and recipient did not induce any prolongation. Furthermore, in order to obtain the optimal beneficial effect of a haplotype-shared blood transfusion, the other haplotype of the transfusion donor had to be mismatched with the recipient. The immunogenetic studies showed that haplotype-shared blood transfusions in combinations where the H2 type of the organ donor differed from that of the transfusion donor are less efficient in inducing prolongation of graft survival. CONCLUSIONS: These results demonstrate that haplotype-shared blood transfusions can induce a significantly prolonged survival of cardiac allografts in F1 mice. The immunogenetic studies suggest that presentation of alloantigen-derived peptides in the context of self MHC (the indirect pathway of allorecognition) is essential for the beneficial effect of haplotype-shared blood transfusions.

Animals↗
PubMed1999

The influence of a partially HLA-matched blood transfusion on the disease activity of rheumatoid arthritis.

OBJECTIVE: Based on the immunosuppressive effects of blood transfusions in organ transplantation, we determined the effect of a blood transfusion on disease activity of rheumatoid arthritis (RA). METHOD: In this double-blind pilot study, 40 patients with active RA were randomly assigned to receive a HLA-DRB1-matched blood transfusion (n = 30) or placebo (n = 10). Disease activity was scored according to the American College of Rheumatology response criteria during 6 months of follow-up. RESULTS: After 1 month and 6 months, respectively, 6 and 16% of patients fulfilled the response criteria in the blood transfusion group compared to none and 30%, respectively, in the placebo group. Following correction for the increase in haemoglobin levels, a majority of the response parameters in the blood transfusion group showed significant improvement compared to the placebo group. CONCLUSION: A DRB1-matched blood transfusion shows improvement of symptoms in several RA patients. Additional studies are required to identify blood transfusion regimens that enhance the potential for therapeutic responses.

Adult↗
PubMed1999

Auto- and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients.

Allogeneic islet transplantation can restore an insulin-independent state in C-peptide-negative type 1 diabetic patients. We recently reported three cases of surviving islet allografts that were implanted in type 1 diabetic patients under maintenance immune suppression for a previous kidney graft. The present study compares islet graft-specific cellular auto- and alloreactivity in peripheral blood from those three recipients and from four patients with failing islet allografts measured over a period of 6 months after portal islet implantation. The three cases that remained C-peptide-positive for >1 year exhibited no signs of alloreactivity, and their autoreactivity to islet autoantigens was only marginally increased. In contrast, rapid failure (<3 weeks) in three other cases was accompanied by increases in precursor frequencies of graft-specific alloreactive T-cells; in one of them, the alloreactivity was preceded by a sharply increased autoreactivity to several islet autoantigens. One recipient had a delayed loss of islet graft function (33 weeks); he did not exhibit signs of graft-specific alloimmunity, but developed a delayed increase in autoreactivity. The parallel between metabolic outcome of human beta-cell allografts and cellular auto- and alloreactivity in peripheral blood suggests a causal relationship. The present study therefore demonstrates that T-cell reactivities in peripheral blood can be used to monitor immune mechanisms, which influence survival of beta-cell allografts in diabetic patients.

Adult↗
PubMed1998

Complete withdrawal of immunosuppression in kidney allograft recipients: a prospective study in rhesus monkeys.

BACKGROUND: We previously reported the successful withdrawal of immunosuppression in kidney-allografted rhesus monkeys. Recipients had received pretransplant blood transfusions and cyclosporine (CsA) immunosuppression for 6 to 12 months. One animal is still alive at more than 15 years after transplantation. Our hypothesis was that the sharing of a single DR antigen between blood donor and recipient, and the sharing of the same DR antigen with the kidney donor, may be beneficial to allograft survival. We now report on the results from a prospective study. METHODS: The animals received three pretransplant blood transfusions from a single donor sharing one DR antigen with the recipient. Subsequently, a life-supporting kidney from a donor sharing the same DR antigen was transplanted. CsA was given for at least 6 months after transplantation. RESULTS: Two animals rejected their graft at 5-8 weeks after cessation of CsA treatment. One animal is still alive at 700 days after transplantation. This animal showed MLR nonreactivity to its kidney donor, similar to the animal at more than 15 years after transplantation. CONCLUSION: These results demonstrate that withdrawal of immunosuppression may be a realistic option in kidney graft patients under careful immunological monitoring of donor-specific immunity.

Animals↗
PubMed1998

[Safety of blood transfusions; need for 'hemo-vigilance'].

Blood transfusion in the Netherlands depends wholly on voluntary donations of blood. Very soon the measures to ensure the safety, the quality and clinical appropriateness of the application of blood products will be re-evaluated. Currently it is not so much viral but bacterial contamination that causes worry, in addition to immunological transfusion reactions. Safety not only depends on freedom from viral or bacterial contamination, but also on the appropriate clinical use of blood products. Physicians will need to document the individual indications for the use of blood products and the patient's reactions at follow-up. European legal harmonisation emphasises look-back procedures and haemovigilance as a means of ensuring sound clinical practice regarding blood transfusion.

Blood↗
PubMed1998

Validation of haplotype frequency estimation methods.

In order to investigate the performance of haplotype frequency estimation methods using unrelated individuals, we compared the results of three estimation methods with those from the haplotypes deduced from family pedigrees. To that end we used the HLA phenotypes of the parents of 1040 families as data for the estimation methods and the full pedigree information as data for the deductive method. We evaluated the results of the following estimation methods: the method using two by two tables described by Mattiuz et al., the maximum likelihood method described by Yasuda and Tsuji and a crude method that uses the information on homozygosity in the phenotypes. All estimation methods generate reliable haplotype frequencies for the more frequent haplotypes, but are unreliable for the less frequent haplotypes. The maximum likelihood estimation method shows the best overall correlation with the results of the deductive method.

Female↗
PubMed1998

Bone Marrow Donors Worldwide and cord blood stem cell transplantation.

Stem cell transplantation using cord blood donors mismatched for one or two HLA antigens can be successful. A simulation study was performed to assess the percentage of patients for whom a matched and/or a one or two antigen mismatched donor is available. Using either bone marrow donors worldwide (BMDW) (n = 925109) or the cord blood donor file in BMDW (n = 11049). As a donor source, for 97% of the Dutch patients a 0 or 1 antigen mismatched cord blood donor was available, for patients from the minority groups this percentage was 55%. These percentages compare favourably with the fraction of 0 mismatched donors found in BMDW.

Blood Banks↗
PubMed1998

An HLA matched donor! An HLA matched donor? What do you mean by: HLA matched donor?

The term 'an HLA matched donor' is in general used without giving exact information on the level of resolution of the HLA typing. This can lead to misunderstandings. A proposal is formulated to agree on using six match categories according to the HLA typing technique used to indicate the level of confidence of the matching.

Bone Marrow Transplantation↗
PubMed1997

HLA gene haplotype frequencies in bone marrow donors worldwide registries.

To calculate reliable HLA gene and haplotype frequencies of bone marrow donors in various regions in the world, we have analyzed the HLA-A, -B, and -DR phenotype frequencies of 18 bone marrow donor registries with a total of more than 300,000 HLA-A, -B-typed donors. These registries were included in the 22nd edition of Bone Marrow Donors Worldwide. Maximum likelihood gene frequencies, Hardy-Weinberg equilibrium fit, and 2- and 3-locus haplotype frequencies were calculated as well as deltas, relative deltas, and their significance. Remarkable gene and haplotype frequency differences exist between the registries. The genetic distances between the different registries were used to draw phylogenetic trees that clearly show that the degree of similarity between registries is related to their geographic locations. The resulting frequencies can be used for the estimation of the probability of finding a hyplotypically identical related or unrelated bone marrow donor for an individual patient. Phylogenetic trees are useful representations of the similarity between donor pools and can also aid in the selection of donors.

Bone Marrow Transplantation↗
PubMed1997

Problems and possible solutions in finding an unrelated bone marrow donor. Results of consecutive searches for 240 Dutch patients.

To evaluate the efficiency of our protocol for finding an HLA matched unrelated bone marrow donor, search results obtained between 1990 and 1995 for 240 Dutch patients were analyzed. The percentage of patients for whom, according to information given by the registries, a fully split-HLA antigen matched donor is available, increased from 24% in 1990 to over 70% in 1995. As a result the percentage of patients transplanted rose from about 24% in 1990-1991 to 44% in 1994-1995. The median time between the start of the search and transplantation was about 6 months. The systematic use of Bone Marrow Donors Worldwide (BMDW) which comprises the HLA groups of all volunteer bone marrow donors in Europe, Israel, South Africa, North America, Canada, India, Australia and New Zealand has been essential in this context. While searching for a suitable donor several problems were encountered such as unavailability of donors (12%) and discordant typing results (8%; range < 1% to > 25%). Thus it is advisable to select several donors for a patient. For 86% of patients with at least one HLA identical donor on the serological level for HLA-A,-B,-DR,-DQ, an HLA-DRB1/3/4/5, and -DQB1 identical donor could be identified. As expected, patients with two frequent haplotypes in strong linkage disequilibrium had the best chance of obtaining an HLA matched donor. Unexpectedly, patients with only one such haplotype had an almost similar chance. It could be calculated that HLA-DR typing of HLA-A,-B identical donors was rarely cost-effective after 1992. Only 12 of the 75 transplanted patients (16%) typeable at DNA level for class II, turned out to be completely matched for HLA-A,-B,-C,-DRB1/3/4/5,-DQB1,-DPB1 and had a negative MLC test. In the group of patients transplanted with a fully matched donor and for whom a CTLp test was performed, only 7% (4/54) of the tests were negative. Search results for patients of non-European origin were dismal, with only four of 26 patients referred being transplanted. In summary, of the 240 patients for whom the Europdonor office searched for a donor, about one-third were transplanted, one-third had a potential donor but did not reach transplantation, while for the remaining one-third of patients no suitable donor could be found.

Adult↗
PubMed1997

Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.

PURPOSE: To compare outcomes of bone marrow transplants for leukemia from HLA-identical siblings, haploidentical HLA-mismatched relatives, and HLA-matched and mismatched unrelated donors. PATIENTS: A total of 2,055 recipients of allogeneic bone marrow transplants for chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the study. Transplants were performed between 1985 and 1991 and reported to the International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA-matched (n = 383) or mismatched for one HLA-A, -B, or -DR antigen (n = 108). HLA typing was performed using serologic techniques. RESULTS: Transplant-related mortality was significantly higher after alternative donor transplants than after HLA-identical sibling transplants. Among patients with early leukemia (CML in chronic phase or acute leukemia in first remission), 3-year transplant-related mortality (+/-SE) was 21% +/- 2% after HLA-identical sibling transplants and greater than 50% after all types of alternative donor transplants studied. Among patients with early leukemia, relative risks of treatment failure (inverse of leukemia-free survival), using HLA-identical sibling transplants as the reference group, were 2.43 (P < .0001) with 1-HLA-antigen-mismatched related donors, 3.79 (P < .0001) with 2-HLA-antigen-mismatched related donors, 2.11 (P < .0001) with HLA-matched unrelated donors, and 3.33 (P < .0001) with 1-HLA-antigen-mismatched unrelated donors. For patients with more advanced leukemia, differences in treatment failure were less striking: 1-HLA-antigen-mismatched relatives, 1.22 (P = not significant [NS]); 2-HLA-antigen-mismatched relatives, 1.81 (P < .0001); HLA-matched unrelated donors, 1.39 (P = .002); and 1-HLA-antigen-mismatched unrelated donors, 1.63 (P = .002). CONCLUSION: Although transplants from alternative donors are effective in some patients with leukemia, treatment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor-recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This difference is less in advanced leukemia.

Age Factors↗
PubMed1996

In vitro sensitivity to prednisolone may predict kidney rejection after steroid withdrawal.

A maintenance immunosuppressive regimen of cyclosporine and steroids after renal transplantation has proven to be a successful policy to obtain long-term graft survival. However, serious side-effects are associated with this therapy; these include an increased risk for infections, cancer, and cardiovascular morbidity and mortality. Therefore, this pilot study was conducted to investigate the possibility of reducing the immunosuppressive load after transplantation. To this end, we tried to develop an in vitro assay to predict graft rejection after withdrawing steroids from the immunosuppressive therapy. Patients who had stable renal function at least one year after transplantation were randomly divided into a group that continued to receive standard immunosuppression of cyclosporine and steroids and a group to be withdrawn from steroid therapy, the latter group being the subject of the present study. Patients withdrawn from steroids were monitored closely and when a biopsy-proven rejection occurred, steroid treatment was reestablished. Blood was collected from patients preceding steroid withdrawal and at fixed time points thereafter. In case of suspected rejection, blood was also taken before biopsy, before steroid treatment was reestablished. In the in vitro limiting dilution analysis-assays cytotoxic T lymphocyte precursor frequencies directed against kidney donor HLA-antigens were determined, in the absence or presence of cyclosporine and several concentrations of prednisolone and the combination of these agents. Confirming earlier results, we found that the number of cyclosporine-resistant cytotoxic T lymphocytes increased prior to a rejection crisis, while they did not change or even decreased in patients who retained normal graft function after steroid withdrawal. More importantly, the results show that 10(-7) M prednisolone in vitro differentially affected donor-specific cytotoxic T lymphocyte precursor frequencies in patients who experienced a rejection crisis after steroid withdrawal, compared with those who remained to do well. This heterogeneity could be detected before the start of steroid withdrawal. Therefore, we conclude that the present data justify a prospective clinical trial to investigate the possible application of this in vitro assay to predict for which patients steroid withdrawal might be considered.

Adult↗
PubMed1996

Association between specific HLA combinations and probability of kidney allograft loss: the taboo concept.

BACKGROUND: HLA matching improves the outcome of cadaveric renal transplantation. However, many allografts function well even in the presence of one or more HLA mismatches, which raises the question of whether some mismatches are better recognised by the recipient's immune system than others. We aimed to identify mismatched HLA donor-recipient combinations that were associated with increased graft loss. METHODS: We selected 2877 first, unrelated renal transplants with a single HLA A, B, or DR mismatch, undertaken between 1982 and 1992, from the Eurotransplant database. To enhance statistical power the analysis was restricted to mismatches of an HLA antigen that occurred in 100 or more donors. 1342 transplants met this criterion and were grouped into a definition set (n = 873) and a validation set (n = 469). In the definition set, we studied further only those recipient HLA antigens that occurred in at least 30 cases within each donor antigen mismatch subset. By a Cox proportional hazards model, donor-recipient combinations that led to significantly higher graft loss than in the whole group were defined. Such combinations were classified as taboo; the remaining combinations were classified as indifferent. FINDINGS: 106 individual recipient antigens were found at least 30 times with a corresponding donor mismatch in the definition set; 11 of the 106 had a significant effect on graft survival. Seven combinations were classified as taboo. Taboo combinations, confirmed as such in the validation set, were associated with graft survival of 81% at one year and 50% at 5 years, significantly lower than the rates in the group with indifferent combinations (89% and 69%; p = 0.04) or among 1190 recipients with no mismatches (89% and 72%; p = 0.03). The findings were substantiated by a multivariate analysis that included the effect of patient immunisation, cold ischaemia time, age, and sex. INTERPRETATION: Mismatched donor antigens are differentially recognised depending on the HLA phenotype of the recipient. The findings may have important clinical consequences for graft survival after transplantation.

Cadaver↗