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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
PubMed1996

The impact of HLA-A matching on long-term survival of renal allografts.

An important contribution of HLA-A antigen matching in renal transplantation was reported initially, hut later publications showed a minor or absent role. We analyzed the contribution of HLA-A locus matching to graft survival in 17,672 first renal transplants from unrelated, nonliving donors. We show that an independent HLA-A matching effect still exists. Due to its relative weakness and late appearance, large numbers and longer follow-up periods are required. The HLA-A matching effect is a significant factor in first renal allograft survival up to 6 years after transplantation, with an increasing effect over time. This is in contrast to the strong, short-lived, effects of HLA-DR and -B matching, which can only be detected up to 6 months and 2 years after transplantation, respectively. A clear additive beneficial effect of HLA-A matching is shown in the group without B and DR mismatches. Therefore, prospective matching for the HLA-A antigens remains important for renal allograft survival.

Graft Survival↗
PubMed1993

Hypothyroidism during immunotherapy with interleukin-2 is associated with antithyroid antibodies and response to treatment.

PURPOSE: We investigated whether the association of interleukin-2 (IL-2) with hypothyroidism is related to the presence of thyroid autoantibodies, dose of IL-2, and clinical effectiveness of treatment, and reviewed the literature. PATIENTS AND METHODS: Sixteen cancer patients were treated with high-dose recombinant, continuous infusion IL-2 (18 x 10(6) IU/m2/d) and lymphokine-activated killer (LAK) cells. One patient previously treated for a toxic goiter with radioactive iodine was analyzed separately. Thyroid function and levels of thyroid antibodies were determined regularly. RESULTS: Seven of 15 patients (47%) became hypothyroid with high serum thyrotropin (TSH) levels within 60 to 120 days after the start of treatment; five responded favorably to treatment (one complete remission [CR], four partial remissions [PRs]), compared with none of the other eight patients. Two hypothyroid patients developed antimicrosomal antibodies (AMAs), one showed a further increase of antithyroglobulin antibodies (TgAbs), and six developed TgAbs. Only one of eight euthyroid patients developed slightly elevated TgAb levels. Development of hypothyroidism correlated significantly with a favorable response to treatment (r = .76, P = .001). The patient, treated with radioactive iodine, also became hypothyroid with high levels of TSH and development of AMAs and TgAbs. No difference was found between the hypothyroid and euthyroid patients in mean cumulative dose of IL-2 administered within the first 60 days or total treatment period, or with the relative dose-intensity. No other autoantibodies were found and patients had normal corticotropin (ACTH) stimulation tests. CONCLUSION: The likelihood of developing (transient) hypothyroidism is higher in patients who respond to IL-2 treatment. The development of antithyroid antibodies suggests that IL-2 treatment triggers autoreactive B-cell clones or that cellular and/or cytokine-mediated thyroid destruction leads to activation of autoreactive B-cell clones.

Adult↗
PubMed1992

Tissue distribution of human minor histocompatibility antigens. Ubiquitous versus restricted tissue distribution indicates heterogeneity among human cytotoxic T lymphocyte-defined non-MHC antigens.

We determined the tissue distribution of 7 human minor histocompatibility (H) Ag. Each of these Ag is defined by one or more MHC class I-restricted CTL clones, previously generated from PBL primed against minor H Ag by HLA-identical bone marrow transplantation (BMT). CTL-mediated lysis of tissue-derived cells and cultured cell lines was used as an in vitro assay for minor H Ag expression of several human tissues. The Ag HA-3 (HLA-A1-restricted), HA-4 (HLA-A2 restricted), HA-6 and HA-7 (HLA-B7 restricted), and the male-specific Ag H-Y (HLA-A2 and B7 restricted) were found to be expressed on cells of all tissues tested. In contrast, the HLA-A2-restricted Ag HA-1 and HA-2 were demonstrated on PHA-blasts, EBV-BLCL, purified T cells, B cells, monocytes, and immature thymocytes, but could not be demonstrated on skin-derived cultured fibroblasts, keratinocytes, melanocytes, cultured epithelial cells of kidney proximal tubili, and umbilical cord vein-derived endothelial cells. Incubation of the latter cell lines with rIFN-gamma, rTNF-alpha, and/or rIL-1 alpha, in concentrations shown to maximally increase their susceptibility to lysis by allo-MHC class I CTL, did not induce recognition by HA-1- and HA-2-specific CTL in vitro. These results indicate an ubiquitous tissue expression of the minor H Ag HA-3, -4, -6, -7 and H-Y in contrast to a to the hemopoietic cell lineage-restricted expression for HA-1 and HA-2. The heterogeneity in tissue expression of T cell-defined, class I-restricted non-MHC Ag implies that they might be derived from intracellular proteins with either an ubiquitous or a more specialized cell type-specific function.

Cytotoxicity, Immunologic↗
PubMed1991

Minor histocompatibility antigens, defined by graft-vs.-host disease-derived cytotoxic T lymphocytes, show variable expression on human skin cells.

Little is known on the effector mechanisms inducing the cutaneous lesions observed during acute graft-vs.-host disease (aGvHD) after allogeneic bone marrow transplantation (BMT). Histological findings have indicated that infiltrating CD8+ lymphocytes probably play a role. We addressed the question of whether host minor histocompatibility (mH) antigen-reactive cytotoxic T lymphocytes (CTL) could account for this phenomenon via direct lysis of the epidermal cell layer. Six CTL clones, obtained from peripheral blood lymphocytes of patients suffering from aGvHD, each recognizing a well-characterized MHC class I-restricted mH antigen epitope, were tested on cultured keratinocytes of nine MHC and mH antigen-typed donors. Four of six mH antigen-specific CTL clones lysed unstimulated MHC class I-expressing, as well as recombinant interferon-gamma (rIFN-gamma)-activated, ICAM-1, MHC class I- and II-expressing keratinocytes. Two strongly cytolytic CTL clones showed no recognition of keratinocytes of donors whose phytohemagglutinin-activated T cell lines were readily lysed. With respect to a GvHD, the results imply that some class I-restricted CTL obtained from peripheral blood lymphocytes of a GvHD patients have the in vitro potential to destroy resting as well as IFN-gamma-activated epidermal cells, whereas others do not. In other words, CTL-defined human mH antigens vary with respect to their expression in the skin. It is intriguing that those minor H antigens which cannot be detected on human keratinocytes in vitro are those known to be associated with the occurrence of GvHD.

Antibodies, Monoclonal↗
PubMed1990

Analysis of the donor-specific cytotoxic T lymphocyte repertoire in a patient with a long term surviving allograft. Frequency, specificity, and phenotype of donor-reactive T cell receptor (TCR)-alpha beta+ and TCR-gamma delta+ clones.

In the present study the transplant specific CTL repertoire of a patient (HLA:A1,3, B8,18, Cw5,7 DR3, DQw2, DPw3) with a long term surviving HLA mismatched kidney graft (HLA: A1,24 B8,27 Cw2,7, DR3, w13 DQw2,6 DPw1,3) has been investigated. This patient was unable to generate specific cytolytic activity against donor-derived PHA-blasts in the MLC in which donor spleen cells or B lymphoblastoid cell line were used as stimulator cells. In addition, the CTL precursor frequencies against donor alloantigens were very low (1/67,000). The patient had otherwise normal immune responses in vivo and in vitro and no signs of transplant rejection. Transplant specific CTL clones were generated in high frequencies (1/195) from T cell bulk cultures activated by PHA in the absence of any sensitization by donor Ag in vitro. The repertoire of 14 donor-reactive CTL clones (12 TCR-alpha beta+ and 2 TCR-gamma delta+) was analyzed. Two TCR-alpha beta+ CD8+ clones were specific for B27. Ten TCR-alpha beta+ CTL clones directed against class II HLA Ag were isolated. Seven of these were CD4+ and recognized DRw13 (3), DQw6 (3), and DPw1 (1), whereas three of these clones were CD4-CD8+ recognizing DRw13 (1) and DQw6 (2). In addition, two donor-specific TCR-gamma delta+ CTL clones were obtained recognizing HLA-A9(23,24) and DQw6. Our data indicate that the precursors of CTL clones specifically directed against donor class I or II HLA Ag are not deleted from the repertoire and that part of this reactivity resides in the TCR-gamma delta+ fraction.

Adult↗
PubMed1989

Analysis of cytotoxic T cell precursor frequencies directed against individual HLA-A and -B alloantigens.

We describe here a limiting dilution analysis to determine cytotoxic T lymphocyte precursor (CTLp) frequencies against individual HLA-A or -B antigens. This assay is reproducible and showed that the CTLp frequency of an individual remains stable with time. Significant variations in CTLp frequency against the same alloantigen were found in different individuals and even in monozygotic twins, showing that these differences were not (completely) genetically determined. Within an individual, a wide range of CTLp frequencies can be found against different allo-antigens. Serologically cross-reactivity seems not to interfere in this assay. This LDA is a practicable tool for a systematic analysis of CTLp response against selected individual HLA-A or -B antigens and can be used for the selection of HLA mismatched donors for transplantation patients.

Cross Reactions↗
PubMed1988

Cellularly defined minor histocompatibility antigens are differentially expressed on human hematopoietic progenitor cells.

Previously, five CTL lines directed against minor histocompatibility (mH) antigens designated HA-1-5 have been established from peripheral blood of patients after allogeneic bone marrow transplantation (BMT), and have been characterized using population and family studies. All cell lines showed specific HLA class I-restricted lysis of PHA-stimulated peripheral blood target cells from donors positive for the particular mH antigens. After 4 h of incubation of the mH antigen HA-3-specific CTL line with bone marrow cells from HA-3+ donors, complete class I-restricted inhibition of colony growth of the hematopoietic progenitor cells was observed even at low E/T ratios, indicating that the HA-3 antigen is strongly expressed on hematopoietic stem cells. Therefore, this antigen may be a target structure in the immune-mediated rejection of the hematopoietic graft in case of incompatibility for this determinant between donor and recipient in allogeneic BMT. In contrast, incubation of bone marrow cells with the antigen-specific anti-HA-1, -2, -4, and -5 CTL lines did not result in growth inhibition of the hematopoietic progenitor cells tested. After a prolonged incubation time and using a very high E/T ratio, progenitor cells from HA-2+ or HA-5+ donors were killed to some extent by the anti-mH-specific CTL lines, although the growth inhibition observed was minor and variable. Our results show that mH antigens are differentially expressed on human hematopoietic progenitor cells. Therefore, only some of these antigens may be targets in immune-mediated rejection of the bone marrow graft.

Cell Line↗
PubMed1988

The effect of mismatching and sharing of HLA-A, -B, and -DR antigens on kidney graft survival in Eurotransplant 1982 to 1988.

1. Cyclosporine significantly improved kidney graft survival by 10-15%. 2. Matching for HLA-DR, HLA-B + DR and HLA-A + B + DR improved kidney graft survival significantly in non-CsA-treated patients. 3. Matching for the HLA-A, -B, and -DR loci, apart and in combination, significantly improved kidney graft survival in CsA-treated patients. 4. The best kidney graft survival was observed in HLA-A + B + DR identical combinations treated with CsA (76% at 5 yrs).

Cyclosporins↗
PubMed1985

Comparison of techniques for the detection of monocyte specific antigens.

Monocyte specific antigens are relevant in renal and bone marrow transplantation, but a reproducible monocyte-antigen system has not yet been recognized. In order to establish a sensitive test system with reproducible results in monocyte serology, 3 different monocyte cytotoxicity techniques were compared. In our hands the two-colour fluorescence test on post-Ficoll total leukocyte suspensions fulfilled the criteria. This technique was used to screen sera from multiparous women and renal transplant recipients for the presence of monocyte specific antibodies. By testing sera on cells from individuals who were HLA compatible with the serum donors, anti-HLA reactions were excluded. Several promising sera containing monocyte specific antibodies were identified, thus indicating the success of our approach.

Antigens↗
PubMed1985

Human hematopoietic progenitor cells in long-term cultures express HLA-DR antigens and lack HLA-DQ antigens.

The expression of HLA-DR antigenic determinants on human hematopoietic progenitor cells (HPC) capable of differentiating into mature blood cells, as determined in semisolid cultures, has been demonstrated previously (3-7). Here, we investigated the expression of class II determinants on HPC responsible for the sustained proliferation of colony-forming units of granulocyte/macrophage (CFU-GM), of multilineage HPC (CFU-GEMM, granulocyte/erythrocyte/macrophage/megakaryocyte), and burst-forming units of erythroid cells (BFU-E) in liquid long-term cultures. Using both fluorescence-activated cell sorting and complement-dependent cytotoxicity assays, HLA-DR determinants could be identified on virtually all these HPC capable of proliferating in long-term cultures. Experiments in which the stromal layer had been irradiated provided evidence that the HPC themselves were truly HLA-DR+, and that the sustained proliferation of HPC was not due to activation of HLA-DR- residual HPC in the stromal layer by reinoculated HLA-DR+ accessory cells. Furthermore, it was shown that all HPC recognized in semisolid and liquid long-term cultures were HLA-DQ-. These results suggest that the human true pluripotential stem cell is HLA-DR+. These results open the possibility of studying class II-dependent regulation of hematopoiesis in liquid long-term cultures.

Cell Division↗
PubMed1984

HLA C associations with acute leukaemia.

Frequencies of HLA A, B, C, and DR antigens were calculated in 1009 leukaemia patients, all of whom had been treated with bone-marrow transplantation and reported to the International Bone Marrow Transplant Registry. Cw3 (relative risk = 2 X 26, p = 0 X 00002) and Cw4 (relative risk = 2 X 18, p = 0 X 00003) were significantly associated with acute leukaemia (p values adjusted for multiple comparisons). Cw3 (relative risk = 2 X 97, p = 0 X 00002) and Cw4 (relative risk = 2 X 10, p = 0 X 004) were also significantly associated with acute lymphoblastic leukaemia and Cw4 was significantly associated with acute myelogenous leukaemia (relative risk = 2 X 39, p = 0 X 0003). The data suggest that Cw3 and Cw4 may be markers for leukaemia susceptibility genes, genes that code for low immune responsiveness to putative leukaemia viruses, or genes that regulate the response to chemotherapy and, therefore, the attainment of remission, since most of these patients underwent transplantation during remission.

Europe↗
PubMed1984

HLA and the rubella-specific immune response following vaccination.

A group of 88 seronegative 11-year-old Dutch girls was selected to be tested for human leukocyte antigens (HLA) and for both the in vivo and in vitro immune response to rubella virus, 6 and 12 weeks after rubella vaccination. Although a slight influence of HLA-associated factors on the antibody levels, as measured by the enzyme-linked immunosorbent assay could not be excluded, no evidence for HLA-associated control of the rubella-specific immune response following vaccination was obtained. From these data it is concluded that HLA-associated factors cannot be expected to hamper the effectiveness of large-scale rubella vaccination procedures.

Antibodies, Viral↗
PubMed1983

Comparison of complement-dependent cytotoxicity and indirect immunofluorescence for enumeration of T-cell subpopulations in human peripheral blood.

The monitoring of T-lymphocyte subsets of recipients of organ grafts enables studies on immune reconstitution (after bone-marrow transplantation) and may predict graft rejection (after kidney transplantation). Quantitation of human peripheral T-lymphocyte subsets from healthy volunteers and from recipients of a bone-marrow graft by a complement dependent cytotoxicity (CDC) assay, based on the use of propidium iodide, and by an indirect immunofluorescence (IIF) technique has been compared using the monoclonal antibodies OKT3, OKT4 and OKT8. Except for OKT3 in healthy individuals--for which no significant difference was found between CDC and IIF--CDC detected significantly more cells of each subset than IIF. Furthermore, the CDC results indicated the presence of low numbers of OKT4+8+ cells in the peripheral blood of healthy individuals and--with higher numbers--following marrow transplantation. Results of depletion experiments, obtained by fluorescence activated cell sorting (FACS) for either OKT4 or OKT8, supported this conclusion. OKT4/OKT8 ratios were calculated from enumerations by the CDC assay and by the IIF assay and found to be linearly related, both in healthy persons and in marrow-graft recipients. Thus, the CDC assay is a reliable method for monitoring T-cell subsets, allowing detection of lymphocytes carrying low densities of membrane determinants.

Antibodies, Monoclonal↗
PubMed1983

Improved fusion technique. I. Human umbilical cord serum, a new and potent growth promoter, compared with other B cell and hybridoma activators.

Accelerated proliferation of hybridoma cells was observed in the presence of human umbilical cord serum (HUCS). This had very strong growth-promoting activity, even at a concentration of 2%. A comparison was made between HUCS and other B cell growth promoters, such as lipopolysaccharide (LPS) and dextran sulfate (DxS), macrophage supernatant, and human endothelial culture supernatant (HECS). The growth-promoting effect of HUCS was superior. Using a microcytotoxicity assay, we found no significant differences in the number of antibody producing clones with the various culture media, except for fetal calf serum.

Animals↗
PubMed1983

Analysis of variability in lymphocyte transformation tests.

To estimate the importance of a number of variables influencing the results of the lymphocyte transformation test (LTT), we analysed retrospectively the results of 250 LTTs on healthy control lymphocytes tested during the last 5 years as part of the routine LTT program. Prospectively, frozen cells from 3 donors were tested together on 5 different occasions. Differences in day-to-day test conditions had only minor influence. The influence of biologic variables was also negligible. The 2 most important factors were intrinsic cell differences, most probably due to damage during freezing, and genetic influences. To demonstrate minor differences between donors or between bleeding dates, repeated testing is necessary to eliminate these intrinsic variables and to allow statistical analysis.

Freezing↗