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F H Claas

Publications and source records attributed to F H Claas.

At least 181 records · Page 10Linked to original sources
PubMed1990

The effect of individual HLA-A and -B mismatches on the generation of cytotoxic T lymphocyte precursors.

In order to study the correlation between HLA mismatches and the cytotoxic T lymphocyte precursor frequency, we used a limiting dilution analysis to determine the CTLp frequencies against individual mismatched HLA-A and -B alloantigens in 21 patients waiting for a renal transplant. Altogether, thirty-three mismatched HLA-A antigens and 55 HLA-B antigens were tested. The CTLp frequencies against mismatches of HLA-B locus antigens were found to be significantly higher than those against HLA-A antigens (P less than 0.002). This may explain why matching for HLA-B antigens is more important for a good renal allograft survival than matching for HLA-A antigens.

Adult↗
PubMed1990

Analysis of the protective effect of topical sunscreens on the UVB-radiation-induced suppression of the mixed-lymphocyte reaction.

The mixed-lymphocyte reaction (MLR) was used to test the protective capacity of several sunscreens against UVB-radiation-induced suppression of the immune response. The MLR was performed using stimulator cells that had been exposed to 120 mJ/cm2 of an UVB source, whereas in simultaneous experiments a sunscreen-covered piece of quartz glass was placed in between the light source and the culture dish. The MLR response after UVB radiation was significantly decreased in comparison with the MLR response of non-radiated cells. This UV effect was partly inhibited by the tested sunscreens, whereas their vehicles alone showed hardly any effect. The protective capacity of sunscreens with similar protection factors, which were determined using the minimal erythematous dose (MED), showed a significant variation. These results suggest that the MED is not an accurate method to determine protection against UV-induced immunologic damage.

Antibody Formation↗
PubMed1989

Effect of one-HLA-DR-antigen-matched and completely HLA-DR-mismatched blood transfusions on survival of heart and kidney allografts.

Blood transfusions can influence the survival of organ allografts favorably, in spite of the danger of sensitization. We investigated the influence of HLA compatibility between blood donors and transfusion recipients on the production of HLA antibodies and on graft survival. Among recipients of transfusions who shared one HLA-DR antigen with their respective donors, antibodies developed in 6 of 28 who had received one transfusion, in 2 of 16 who had received three transfusions, and in 4 of 24 who had undergone renal transplantation. Among recipients who were mismatched with their donors for both HLA-DR antigens, the rate of sensitization was significantly higher in all three of these groups (18 of 30, P = 0.02; 12 of 16, P = 0.0007; and 12 of 22, P = 0.001). The survival of kidney allografts among graft recipients who were given transfusions and shared one HLA-DR antigen with their blood donors (81 percent at five years) was significantly higher than among recipients who were given transfusions and were mismatched for both HLA-DR antigens (57 percent; P = 0.02) or among recipients who were not given transfusions (45 percent; P = 0.001). There was no difference in graft survival between patients who received transfusions mismatched for two HLA-DR antigens and those who were not given transfusions. We conclude that allograft survival can be improved by pretransplantation blood transfusion when the transfusion recipients share at least one HLA-DR antigen with their donors. In view of the increased rate of sensitization and the lack of improvement in graft survival, the transfusion of blood mismatched for two HLA-DR antigens appears to be contraindicated in candidates for transplantation.

Antibody Formation↗
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↗
PubMed1989

Drug-induced agranulocytosis: review of possible mechanisms, and prospects for clozapine studies.

Although toxicity and inborn errors of metabolism may also be involved, immunological reactions play an important role in the induction of drug-induced agranulocytosis. Drug-induced antibodies may lead to agranulocytosis by at least three different immunological mechanisms. Immune complexes may selectively adhere to granulocytes or their immature precursor cells, the drug may bind to the granulocytes as carriers of the immunogenic drug and finally the drug may induce antibodies directed to granulocyte-specific structures. The use and the interpretation of in vitro assays to detect drug-dependent antibodies against granulocytes or myeloid precursor cells are discussed. These assays will be used to detect a possible immunological mechanism involved in clozapine-induced agranulocytosis. Further studies will concern the identification of possible genetic risk factors associated with clozapine-induced agranulocytosis.

Agranulocytosis↗
PubMed1989

Specific suppression of mixed lymphocyte reactions by alloactivated cells is correlated with cytotoxicity.

Mixed lymphocyte reaction (MLR)-activated lymphoblasts can suppress both proliferation and the induction of cell-mediated lysis (CML) when added to a subsequent MLR. Antigen specificity and the mechanism of MLR-induced suppression was investigated, with special emphasis on the exclusion of cell-mediated stimulator cell lysis as the cause of suppression. We studied the suppressive properties of nine MLR-activated cultures, selected because of their specific suppressive properties. Suppression of a given MLR was obtained when the stimulator cell carried at least one of the mismatched HLA antigens of the original stimulator. The mismatched antigen which activated suppression was an HLA class I antigen in 3 out of 9 cases, an HLA class II antigen in another 3 cases. In the remaining 3 cases suppression was observed when either an HLA class I or an HLA class II antigen was shared between the original stimulator and stimulator cell of the MLR. When analyzed on the same panel, a positive linear correlation between suppression of an MLR and CML activity against the stimulator cell was found. We also observed that both the original MLR (A*B) and the reserve MLR (B*A) could be suppressed by these anti-A suppressor cells. These results are compatible with the hypothesis that in the protocol studied suppression is mediated by lysis of the stimulator cells.

Cytotoxicity, Immunologic↗
PubMed1989

Acquired Zwa antigen on Zwa negative platelets demonstrated by western blotting.

Zwa-negative platelets that had been incubated in random donor AB plasma for several hours and subsequently cryopreserved, were found to be Zwa-positive when tested 3 years later by Western blotting. Following this serendipitous observation, we demonstrated that the Zwa antigen could be passively adsorbed onto the membrane of Zwa-negative platelets incubating for 4 h in the plasma from Zwa-positive donors. This observation supports the hypothesis that passive acquirement of Zwa antigens is a pathogenic mechanism for inducing post-tranfusion purpura, and suggests that Zwa-negative platelets should not be stored in Zwa-positive plasma before transfusion.

Adult↗
PubMed1989

Cytotoxic T lymphocytes are the prime mediators of suppression of the mixed lymphocyte reaction by alloactivated cells.

An alloactivated secondary mixed lymphocyte reaction (MLR) culture (SMC), which was suppressive in the MLR with autologous responder cells, was studied in more detail. In particular, we investigated whether the suppressive activity of this SMC was mediated by cytotoxic T cells or whether bona fide suppressor cells were involved. The SMC suppressed an MLR when the stimulator cells shared Bw57, Bw60, or Dw19 with the original stimulator. Separation of the SMC into CD4+ and CD8+ fractions demonstrated that the CD8+ fraction contained suppressive and cytotoxic activity against Bw57 or Bw60 antigens, while the CD4+ fraction contained both activities against the Dw19 specificity. The CD8+ fraction was also suppressive in the reverse MLR, while the CD4+ fraction was not. Limiting dilution analysis demonstrated that all CD8+-suppressive cultures were also cytotoxic, whereas in the CD4+ fraction both cytotoxic and non-cytotoxic suppressor cultures were found.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Hyperimmunized patients do not need to wait for an HLA identical donor.

Hyperimmunized patients tend to accumulate on renal transplant waiting lists because their high level of sensitization leads to positive crossmatches with almost all potential organ donors. The origins of sensitization and the different efforts made to find cross-match negative donors for these patients are discussed. Special emphasis is given to a local strategy based on the determination of HLA-A and -B mismatches, against which the patient did not form allo-antibodies, the so-called acceptable mismatches. Kidney donor selection is based on compatibility with the patient's own HLA-antigens in combination with the acceptable HLA-A and -B antigens, and can be operated from a central organ-sharing office. The acceptable HLA mismatches are often identical with or include the non-inherited HLA class I antigens of the mother (non-inherited maternal antigens: NIMA).

Female↗
PubMed1989

Transplantation of highly sensitized patients on the basis of acceptable HLA-A and B mismatches.

We think that the determination of acceptable mismatches is an efficient approach to increase the chance of finding a crossmatch-negative donor for highly sensitized patients. This approach has several advantages (4,5) namely: 1. There is no need for distribution of patient sera to other tissue typing centers. 2. Rather than performing crossmatches with all donors, most of which will be positive, selection is based on a predictable negative crossmatch. 3. Selection of potential donors is based on data obtained by the recipient centers, which has all the information concerning the patient's immunological background (transfusion, specific alloantibodies, autoantibodies) rather than on a negative crossmatch at another tissue typing center. 4. Selection is based on HLA-DR compatibility between donor and recipient, which is, both in our and other analyses (6), important for an optimal prognosis of graft survival in highly immunized patients. Of course, there are still patients for whom this protocol is not very helpful (rare HLA-types, hardly any or no acceptable mismatches). For these patients it might be that other approaches, including removal of circulating antibodies (7), may be the only solution.

Clinical Protocols↗
PubMed1989

Transplantation in hyperimmunized patients.

The accumulation of highly sensitized patients on waiting lists for renal transplantation is a universal problem. Because these patients have alloantibodies against many HLA alloantigens, it is difficult to find a cross-match-negative graft for them. As a result, their average waiting time is much longer than that of patients with fewer or no alloantibodies. Also, because the outcome of transplantation in highly immunized patients is generally less good, the result is a relatively great number of highly sensitized patients returned to the waiting list for retransplantation. In this paper we will deal with three topics: Why patients become highly sensitized, and what strategies are available to increase the chance of finding a donor for highly immunized patients, comprise two topics. The third is the description of a special strategy developed in our center to predict and select cross-match-negative donors for highly sensitized patients.

HLA Antigens↗
PubMed1989

Increase of donor-specific cytotoxic T lymphocyte precursors after transfusion.

Cytotoxic T lymphocyte precursor (CTLp) frequencies were determined in the blood of 10 patients before and after transfusion. The male patients were selected from those on the waiting list for a heart or kidney transplantation, who had received no previous blood transfusions and had no panel-reactive antibodies. Both the limiting dilution curves obtained before as well as after transfusion were linear and applied to zero-order kinetics, indicating that only cytotoxic T cells were limiting in the assay. In 9 out of 10 patients CTLp frequencies against the blood donor antigens significantly increased (up to 107 times) compared to the CTLp frequencies measured before transplantation. The CTLp frequencies against controls, sharing no HLA antigens with the blood transfusion donor, were only slightly increased (up to 5 times) in 7 patients and decreased in 3.

Blood Transfusion↗