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Biomedical subjects

F H Claas

Publications and source records attributed to F H Claas.

At least 163 records · Page 9Linked to original sources
PubMed1992

No direct clinical relevance of the human leucocyte antigen (HLA) system in clozapine-induced agranulocytosis.

The clinical use of clozapine in psychiatry is restricted by the associated risk of agranulocytosis. This risk is significantly higher than that associated with conventional antipsychotic medications. In order to identify a possible parameter to detect susceptible individuals before treatment, 103 patients with a history of clozapine-induced granulocytopenia or agranulocytosis and 95 matched control patients were typed for human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and for a number of neutrophil-specific alloantigens. No significant association between certain HLA alleles or neutrophil antigens and susceptibility to clozapine-induced granulocytopenia or agranulocytosis was observed.

Agranulocytosis↗
PubMed1991

Relation between skin cancer and HLA antigens in renal-transplant recipients.

BACKGROUND: Recipients of renal allografts are at an increased risk for skin cancer. It is also known that recipients who are homozygous for HLA antigens are at an increased risk for certain cancers, as are those who are mismatched with their donors for these antigens. In a case-control study we assessed the relation between skin cancer in renal-transplant recipients and HLA homozygosity and mismatching. METHODS: Of 764 patients who received renal transplants between 1966 and 1988, 66 had squamous-cell carcinoma or basal-cell carcinoma of the skin after transplantation. HLA homozygosity was assessed in all 66 recipients, and HLA mismatching in 39; the results were compared with those in 124 recipients without skin cancer. We also investigated the relation between skin cancer and the use of immunosuppressive drugs. In separate case-control analyses we investigated the influence of exposure to the sun and keratotic skin lesions on the risk of skin cancer. RESULTS: The risk of squamous-cell carcinoma was increased in recipients mismatched for HLA-B antigens; the relative risks were 2.6 (95 percent confidence interval, 1.1 to 6.5) and 5.0 (95 percent confidence interval, 1.3 to 19.0) with mismatching for one and two antigens, respectively, as compared with no mismatching. Mismatching for HLA-A or HLA-DR antigens had no effect on the risk of squamous-cell carcinoma, and there was no association between mismatches at any of the HLA loci and the occurrence of basal-cell carcinoma. The total doses of azathioprine and prednisone were not associated with the occurrence of skin cancer or with HLA matching. Exposure to sunlight and keratotic skin lesions were strongly associated with skin cancer but not with HLA mismatching. Homozygosity for HLA-DR was more frequent among the patients with squamous-cell carcinoma (relative risk, 2.5; 95 percent confidence interval, 0.95 to 4.6) and among patients with 100 or more keratotic skin lesions (relative risk, 4.8; 95 percent confidence interval, 1.5 to 15.1). CONCLUSIONS: HLA-B mismatching is significantly associated with the risk of squamous-cell carcinoma in renal-transplant recipients, as is HLA-DR homozygosity. An indirect effect on the level of immunosuppression does not appear to explain these findings, nor does exposure to sunlight or the number of keratotic skin lesions account for this observation.

Adult↗
PubMed1991

Phenotypic and functional analysis of T cell receptor gamma delta-bearing cells isolated from human heart allografts.

Endomyocardial biopsies from human heart transplant recipients were investigated with respect to the occurrence of in vivo activated, alloreactive TCR-gamma delta+ cells. More than one year after transplantation, 30% of the biopsy-derived T cell cultures contained TCR-gamma delta+ cells, whereas in the first year after heart transplant in only 8% of the culture TCR-gamma delta+ cells were found. Such an increase of TCR-gamma delta+ cells was not observed in the peripheral blood of the patient. In most biopsy-derived cultures, the gamma delta cells were delta-TCS1+. No donor-specific cytotoxic activity could be demonstrated for TCR-gamma delta+ cells tested, whereas non-MHC-restricted cytotoxicity was found in several cultures. The occurrence of nonalloreactive TCR-gamma delta+ cells late after transplantation, when acute cellular rejection episodes are rare, suggests a role in the down-regulation of the allo-Ir.

Cells, Cultured↗
PubMed1991

Negative cross-match selection of HLA-DR compatible kidneys for highly sensitised patients.

Patients who have developed alloantibodies against almost all foreign HLA antigens are very difficult to transplant, because the cross-match with potential donors is often positive. The ideal donor for such patients is an HLA identical or compatible donor, but due to the enormous polymorphism of the HLA complex, the chance of finding such a donor is very small. The acceptable mismatch program, which takes advantage of the HLA-A and B antigens toward which the patient has not developed antibodies, and HLA-DR matching in the computerised selection of kidney donors, has significantly decreased the waiting time for these highly sensitised patients. Furthermore, graft survival is similar to that of non-highly sensitised patients.

Graft Survival↗
PubMed1991

Alloreactive lymphoid infiltrates in human heart transplants. Loss of class II-directed cytotoxicity more than 3 months after transplantation.

From 535 endomyocardial biopsies (87 heart transplant recipients) 283 cell cultures could be generated. All cultures tested contained T lymphocytes and in most cases CD4 was the predominant phenotype at any time posttransplant. A significantly higher proportion of CD8-dominated cultures was found among cultures from biopsies without myocytolysis. In the first 3 months post transplant 57% of cultures showed cytotoxicity against both class I and class II mismatched donor major histocompatibility complex (MHC) antigens, changing to an incidence of 33% at greater than 90 days. This proved to be due to a significant decrease in the number of cultures with human leukocyte antigen class II-directed cytotoxicity. This study shows that early after transplantation a heart transplant is infiltrated with activated donor-specific cytotoxic T cells which recognize a broad spectrum of mismatched donor MHC antigens, and that in time this spectrum becomes more restricted.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

On a possible protective effect of HLA-A11 against skin cancer and keratotic skin lesions in renal transplant recipients.

Renal transplant recipients who have skin cancer potentially related to human papillomavirus were HLA typed with a special focus on HLA-A11, which in nonimmunosuppressed patients is negatively associated with the occurrence of virus-related carcinoma of the cervix. We found also a negative association between HLA-A11 and skin cancer; none of the 66 transplant recipients with skin cancer were positive for HLA-A11. As HLA-A11 seems to have a protective effect against skin cancer, we speculate that antigens induced by squamous cell carcinomas and possibly also by human papillomavirus may be efficiently presented through HLA-A11 to cytotoxic T cells. We also investigated a possible influence of other HLA alleles on the susceptibility of renal transplant recipients to skin cancer. The frequency of HLA-B27 was significantly higher in the transplant recipients with skin cancer, with a relative risk of 3.4 relative to healthy controls. No significant differences were found for other HLA class I or class II antigens.

Alleles↗
PubMed1991

Effect of topical sunscreens on the UV-radiation-induced suppression of the alloactivating capacity in human skin in vivo.

Exposure of mice or humans to solar or artificial ultraviolet radiation (UV) has been shown to induce a number of changes in the immune system that may influence their susceptibility to skin tumors. The protective effect of sunscreens on these changes is not clear. Thirty-two patients with a variety of dermatoses routinely undergoing treatment with standard UVB (n = 19) or PUVA (n = 13) therapy were studied. One of the two tested sunscreens or its vehicle was applied to the right flexor forearm immediately prior to each total-body UV exposure. Epidermal sheets were obtained by the suction-blister method from the left flexor forearm before treatment and from both flexor forearms after 4 weeks of photo- or photochemotherapy and used as stimulator epidermal cells (EC) in the mixed epidermal cell-lymphocyte reaction (MECLR). After 4 weeks of either UVB or PUVA therapy the MECLR responses on EC from both arms were markedly decreased. Neither the tested sunscreens nor their vehicles prevented the UV-induced suppression of the alloactivating capacity. The failure of sunscreens to protect against the UV-induced suppression of the alloactivating capacity could be explained in two ways. First, the energy not absorbed by the sunscreen could be sufficient to induce suppression of the alloactivating capacity. An alternative explanation could be systemic immune suppression by UV. In order to discriminate between these possibilities only the right forearms of 10 healthy volunteers, treated with a sunscreen or its vehicle, were irradiated with UVB during 4 weeks. In this manner systemic immune suppression by UVB could be excluded. This experiment resulted in a similar suppression of the MECLR responses, as induced by total body UVB irradiation, without any protection by the sunscreen. Apparently, the UV dose not absorbed by the sunscreen was capable to induce suppression of the alloactivating capacity. Our results indicate that people protected from sunburn by sunscreens may be exposed to UV for a long period of time, and thereby subject themselves to its immunosuppressive action.

Administration, Topical↗
PubMed1990

The influence of allogeneic cells on the human T and B cell repertoire.

Clinical transplantation is often complicated by rejection episodes, in which the immune system of the recipient reacts to the foreign transplantation (HLA) antigens on the graft. This immune response includes humoral and cellular components. In the first, B lymphocytes form antibodies to the HLA alloantigens. In the second, CD8+ T lymphocytes recognize and react to HLA class I antigens, and CD4+ T cells react to HLA class II antigens. The frequency and severity of these rejection episodes can be diminished by immunosuppressive drugs, HLA matching between donor and recipient, and immune modulation by blood transfusion. Effective HLA matching between donor and recipient is not always possible and often not necessary. Insight into the factors that influence the T and B cell repertoire after blood transfusion might lead to new approaches to improve graft survival.

B-Lymphocytes↗
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↗
PubMed1990

gamma delta T-cell receptor-positive T-cell clones derived from human heart transplants do not show donor-specific cytotoxicity.

gamma delta T-cell receptor-positive T-cell clones were obtained from three endomyocardial biopsies taken from two patients. Clones obtained from two biopsies from patient A, one taken during rejection and one after resolution of this rejection, were WT31-, 11F2+, Ti gamma A-, delta TcS1+. Clones from patient B grown from a biopsy without histologic signs of rejection were either WT31-, 11F2+, Ti gamma A+, delta TcS1-, or WT31+. All gamma delta T-cell receptor-positive clones had cytolytic potential but did not demonstrate donor-specific lysis.

Biopsy↗
PubMed1990

Subtypes of HLA-A1 defined on the basis of CTL precursor frequencies.

Recently we have shown that limiting dilution analysis can be used to detect cytotoxic T-cell precursor frequencies directed against individual HLA class I antigens. Using the same protocol, we have been able to define two subtypes of HLA-A1, which are indistinguishable by conventional typing sera as well as by cell-mediated lympholysis. One-dimensional isoelectric focusing analysis of the variants did not show any overall charge differences. However, family studies indicated that these HLA-A1 subtypes are genetically determined and can be distinguished on the bases of T-cell precursor frequencies in HLA-A1-negative blood donors.

Binding, Competitive↗
PubMed1990

Immunological unresponsiveness induced by ultraviolet-B-irradiated and nonirradiated skin grafts.

We previously reported that ultraviolet-B-irradiated B10.AQR tail skin grafts were permanently accepted by B10.T6R recipients in about half the cases. Such a beneficial effect on graft survival could only be demonstrated in this particular combination. We have now investigated whether these animals had become tolerant to the donor strain antigens. Nonirradiated B10.AQR tail skin grafted 50 days after acceptance of a UVB-irradiated B10.AQR graft was accepted in 9/9 cases, indicating that these animals had become tolerant to the B10.AQR alloantigens. However, secondary grafts on animals that had rejected the first graft also showed a prolonged or definite survival. This tolerance was specific; B10.T6R mice tolerant to B10.AQR grafts rejected B10 skin grafts, while F1(B10A X B10.AQR) and F1(B10 X B10A) grafts, sharing class II antigens with B10.AQR, had a slightly prolonged graft survival. Cells of tolerant animals showed normal proliferative responses against B10.AQR antigens. However, when autologous serum was added, proliferation was specifically suppressed. Likewise, this specific tolerance could be transferred with serum or serum and cells but not with cells only. Analysis of the sera of these animals showed long-lasting and donor-specific high-titered cytotoxic antibody titers, which are likely to play a pivotal role in the observed suppression.

Animals↗
PubMed1990

An increase of donor-specific T helper precursors resulting from blood transfusions.

In order to study the effect of blood transfusions on the donor-specific helper T cell repertoire, donor-specific interleukin 2-producing precursors (Th precursors [Thp]) were examined in 10 patients before and after transfusion. These patients were selected to be male, had received no previous transfusions or transplantation, and had no cytotoxic antibodies against MHC antigens in their serum. The limiting dilution curves were linear before as well as after transfusion, showing that only the cell under study was limiting. It was found that the transfusion donor-specific Thp frequencies increased significantly after transplantation in 10 of 10 patients (ratio: 1.5 to 7.1). In addition, the IL-2 production by individual clones tended to be higher after transfusion. In contrast, Thp frequencies against a third-party control showed a small increase in 4 and was unchanged in 6 patients. These data indicate that blood transfusions prime the donor-specific Th compartment.

Blood Transfusion↗