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F H Claas

Publications and source records attributed to F H Claas.

At least 109 records · Page 6Linked to original sources
PubMed1996

A cell-saving non-radioactive limiting dilution analysis-assay for the combined determination of helper and cytotoxic T lymphocyte precursor frequencies.

We have developed a limiting dilution analysis-assay which makes the determination of both helper and cytotoxic T lymphocyte precursor frequencies possible. The way in which T helper precursor frequencies are determined in this combined assay is essentially the same as the method published previously. Experimental conditions for the combined assay have been optimized to obtain cytotoxic T lymphocyte precursor frequencies that are comparable to those determined in the assay routinely used in our laboratory. For all situations where the amount of available cell material is a limiting factor, it will be an advantage that with the same number of cells needed for a standard cytotoxic T lymphocyte precursor frequency determination, in the combined assay both helper and cytotoxic T lymphocyte precursor frequencies can be determined. This is especially convenient in the case of bone marrow transplantation, where evidence is accumulating that low or negative cytotoxic T lymphocyte and/or T helper precursor frequencies may be a prerequisite for a successful transplantation with a minimal risk of graft-versus-host disease.

Hematopoietic Stem Cells↗
PubMed1996

Membrane-bound regulators of complement activation in uveal melanomas. CD46, CD55, and CD59 in uveal melanomas.

PURPOSE: To identify the presence of membrane-bound regulators of complement activation (m-RCA) on uveal melanomas and uveal melanoma cell lines and to examine their role in the inhibition of complement-mediated lysis in vitro. METHODS: Immunohistochemistry and flow cytometric analysis with monoclonal antibodies directed against m-RCA CD46, CD55, and CD59 were applied to tissue sections of 10 uveal melanomas, three primary uveal melanoma cell lines, and one uveal melanoma metastatic cell line. A microcytotoxicity test was used for measuring antibody-dependent complement-mediated lysis. RESULTS: The tissue sections and all four uveal melanoma cell lines expressed CD46, CD55, and CD59. Complement-mediated lysis in the presence of human complement was increased after partial removal of the m-RCA CD55 and CD59 with phosphatidylinositol-specific phospholipase C from the uveal melanoma cell line 92-1. CONCLUSIONS: These results demonstrate that CD46, CD55, and CD59 are expressed in uveal melanomas and that CD55 or CD59, or both, plays a role in resistance to complement-mediated cytotoxicity. The finding that m-RCA are expressed in uveal melanomas may have implications for the effectiveness of the anti-tumor response and in the therapeutic application of monoclonal antibodies directed against tumor-associated antigens.

Aged↗
PubMed1996

Donor-derived human leukocyte antigen class I proteins in the serum of heart transplant recipients.

BACKGROUND: Human leukocyte antigen class I proteins are expressed on most cell types in all organ allografts but are constitutively secreted only by certain organs, for example, the liver. We hypothesized that detectable levels of donor-derived human leukocyte antigen proteins would be released from transplanted cardiac allografts only when the allograft was immunologically stimulated, that is, during rejection and perhaps during viral infection. If so, then the release of donor human leukocyte antigen might be a noninvasive monitor of these events. METHODS: We used an enzyme-linked immunosorbent assay to detect donor-derived human leukocyte antigen-A2 in the serum of 21 human leukocyte antigen-A2 negative recipients of human leukocyte antigen-A2-positive heart transplants. The level of donor human leukocyte antigen-A2 during the first 100 days after transplantation was correlated with the clinical status of the patient. RESULTS: We found little or no donor human leukocyte antigen in the serum of heart transplant recipients whose postoperative clinical course was unremarkable for infection or rejection. We did find donor-derived human leukocyte antigen in the serum of heart transplant recipients transiently in the week immediately after transplantation, continuously from patients in whom chronic rejection was developing, during cytomegalovirus infection, and during some, but not all, acute rejection episodes as determined by endomyocardial biopsy. CONCLUSIONS: These findings are consistent with the hypothesis that the donor human leukocyte antigen serum level reflects vascular diseases, rather than myocardial disease in the transplanted heart. Therefore, the serum level of donor human leukocyte antigen cannot be used as a monitor of cellular infiltration and myocyte damage as currently assessed by endomyocardial biopsy but may be an early indicator of the development of vascular disease such as chronic rejection.

Biopsy↗
PubMed1996

Long-term results of solid organ transplantation. Report from the Eurotransplant International Foundation.

Graft survival of cadaveric kidney-only, liver-only and heart-only transplants, performed in the Eurotransplant area between 1987-1990, was analysed, up to 5 years after transplantation. 1. HLA-A,-B,-DR mismatches had a statistically significant adverse influence on renal graft survival. 2. Kidney retransplantation was not found to be associated with a higher risk of graft loss, in contrast to liver and heart retransplantation. 3. The use of non-ideal donors (aged under 16 or over 55, non-head trauma donors) in renal transplantation should be re-evaluated, while elderly donors as well as elderly recipients jeopardized liver and heart transplant success rates. 4. A learning phase in liver and heart transplantation was evident from 1987-1990. 5. Time-effect studies can be used to adopt individual monitoring schemes. A persistent risk of graft loss in renal transplantation was observed for transplants from older donors and transplants in older recipients; these grafts constituted a very vulnerable group. For liver and heart retransplants it was noted that once patients had survived the first postoperative month, their relative risk of graft failure was no longer significantly different from patients with a first transplant. A well-considered long-term monitoring scheme for heart allograft recipients who are over age 55 is justified, as these patients had a higher risk of failure compared with younger patients. The same would be advantageous for liver transplants that are performed because of underlying liver malignancies.

Adolescent↗
PubMed1995

No evidence of an influence of the noninherited maternal HLA antigens on the alloreactive T cell repertoire in healthy individuals.

In order to test whether a selective T cell nonresponsiveness to noninherited maternal human leukocyte antigens (NIM) exists, we measured the frequencies of alloreactive T cells of healthy individuals to their NIM HLA antigens and to their noninherited paternal (NIP) HLA antigens by limiting dilution assays. Both the frequencies of cytotoxic T cell precursors (CTLp) and IL-2-producing helper T cell precursors (HTLp) were determined. Similar frequencies were observed for NIM class I-reactive CTLp and NIP class I-reactive CTLp. This was the case when frequencies were determined against total NIM and NIP haplotypes but also when CTLp frequencies against individual NIM and NIP antigens were measured. A positive finding of this study was the confirmation of our earlier observation that CTLp frequencies against individual HLA-A antigens are generally lower than CTLp frequencies against HLA-B. This was found both for the maternal and the paternal HLA-A and -B antigens. Similarly, comparable frequencies of IL-2-producing helper T cell precursors directed against NIM HLA class II antigens and NIP HLA class II antigens were found. When breast-feeding in the neonatal period was considered, no differences in the frequencies of CTLp and HTLp were observed between children who had been breast-fed and children who had not. Therefore the present data do not support the hypothesis that confrontation with noninherited maternal HLA in neonatal life leads to down-regulation of alloreactive T cell responses to the mother.

Adult↗
PubMed1995

Relevance of pretransplant donor-specific T cell allorepertoire for human kidney graft survival.

In order to determine whether the donor-specific T cell allorepertoire evaluated in patients before transplantation can be predictive for kidney graft survival, a study has been set up in which the number and activation state of donor-specific T lymphocytes before transplantation were correlated to transplant survival time. Limiting dilution analysis assays were carried out to determine precursor frequencies of both T helper and cytotoxic T lymphocytes. The activation state of these cells was studied by evaluating the inhibitory capacity of cyclosporine on helper and cytotoxic T cells and/or a monoclonal antibody directed against CD8 on cytotoxic T cells. This study shows that neither a significant difference in the number nor activation state of donor-directed helper and cytotoxic T cells before transplantation could be detected when patients who acutely rejected their grafts were compared with patients who still had a well-functioning kidney graft after more than 10 years. Moreover, no significant differences in the donor-specific T cell repertoire were found when patients who had been subject to multiple rejection episodes were compared with patients who experienced few complications after transplantation. Therefore, we conclude that in individuals who have not been sensitized to HLA antigens of the donor, the donor-specific peripheral T cell allorepertoire prior to transplantation is not predictive of kidney graft survival.

Antibodies↗
PubMed1995

The presence of activated donor HLA class I-reactive T lymphocytes is associated with rejection of corneal grafts.

Although the cornea is considered to be an immunological privileged site, corneal transplantation can result in immunological rejection followed by graft failure, especially in patients with vascularized corneas. Several studies suggest a beneficial effect of matching for the HLA class I antigens on corneal graft survival, although a large study (the Collaborative Corneal Transplantation Study) failed to confirm this. To circumvent an endless discussion on studies either confirming or denying the relevance of HLA matching, we decided to approach this problem in another way. A more direct way to assess the importance of HLA class I antigens in corneal transplantation is to measure whether rejection of an allograft is associated with priming of cytotoxic T lymphocytes recognizing the mismatched HLA antigens of the donor. In the present study, 13 patients with good graft function and 10 with ongoing rejection of their corneal allografts were analyzed for the presence of CTL directed against mismatched donor HLA class I antigens, by limiting dilution assays. CTLs were divided into naive and primed CTLs based on the measurement of their in vitro sensitivity or resistance to anti-CD8 or cyclosporine. Cytotoxic T cell precursor frequencies directed against the mismatched donor HLA class I antigens were similar in nonrejectors and rejectors. However, rejection was strongly associated with the presence of primed, donor-specific CTL, whereas these primed cells were absent in case of good graft function. These data show that HLA antigens of a transplanted cornea are immunogenic and targets for rejection by cytotoxic T cells. Therefore, this study supports the need for HLA-A and -B matching in corneal transplantation in patients with a high probability of rejection.

Antibodies↗
PubMed1995

Occurrence of allogeneic HLA and non-HLA antibodies after transfusion of prestorage filtered platelets and red blood cells: a prospective study.

The incidence and consequences of HLA and non-HLA immunization were evaluated in 229 patients with aplastic thrombocytopenia. All patients were transfused with prestorage filtered red blood cells and platelets. On admission, 29 patients presented with HLA antibodies due to prior immunization by pregnancy and/or blood transfusions. Of the 200 patients showing no detectable HLA antibodies on admission, 164 could be evaluated. HLA antibodies developed in 2.7% (3 of 112) of the patients with a negative risk history of prior immunization. The occurrence of HLA antibodies in patients with a history of previous pregnancies or prior non-leukocyte-depleted blood transfusions (risk history positive) was 31% (16 of 52). Of the total of 48 patients who were or became alloimmunized, 92% (44 of 48) had a positive risk history. Ten patients with broad multispecific HLA antibodies with a panel reactivity (PRA) of greater than 70% required transfusions with HLA-matched platelets. Patients with HLA antibodies with lower PRA could be supported by random donor platelets. Two patients developed platelet-specific antibodies, causing transfusion refractoriness that necessitated selecting platelets by the absence of a platelet-specific antigen. Using prestorage leukocyte depletion of red cells and platelets with less than 5 x 10(6) residual leukocytes, 95% of the patients, including patients with a previous risk history or with HLA antibodies with low PRA, can be supported with random donor transfusions for the entire duration of their thrombocytopenic periods.

Abdominal Pain↗
PubMed1995

Leukocyte depletion of random single-donor platelet transfusions does not prevent secondary human leukocyte antigen-alloimmunization and refractoriness: a randomized prospective study.

We studied the value of leukocyte depletion of platelet transfusions for the prevention of secondary human leukocyte antigen (HLA)-alloimmunization in patients with a high-risk of prior immunization induced by pregnancies. Seventy-five female patients with hematologic malignancies (mostly acute leukemia) and a history of pregnancy were randomized to receive either standard random single-donor platelet transfusions (mean leukocytes, 430 x 10(6) per transfusion) or leukocyte-depleted random single-donor platelet transfusions. Leukocyte depletion to less than 5 x 10(6) leukocytes per platelet transfusion (mean leukocytes, 2 x 10(6) per transfusion) was achieved by filtration. Of the 62 evaluable patients, refractoriness to random donor platelets occurred in 41% (14 of 34) of the patients in the standard group and in 29% (8 of 28) of the patients in the filtered group (P = .52); anti-HLA antibodies developed in 43% (9 of 21) of individuals in the standard group and 44% (11 of 25) of cases in the filtered group. The time toward refractoriness and development of anti-HLA antibodies was similar for both groups. We conclude that leukocyte depletion of random single-donor platelet products to less than 5 x 10(6) per transfusion does not reduce the incidence of refractoriness to random donor platelet transfusion because of boostering of anti-HLA antibodies.

Adult↗
PubMed1995

Human leucocyte antigen phenotypes and gold-induced remissions in patients with rheumatoid arthritis.

To assess possible associations between human leucocyte antigens (HLA) and the achievement of remission during gold treatment, HLA typing was performed in 67 rheumatoid arthritis (RA) patients with a gold-induced remission and in 25 control RA patients who discontinued gold therapy because of lack of efficacy. Both groups of RA patients showed a significantly higher frequency of DR4 antigen and lower frequency of DR6 than a control population. There were no significant differences in HLA antigens between remission-responders and non-responders. It is concluded that HLA typing is not helpful in predicting the therapeutic response to parenteral gold therapy.

Adult↗
PubMed1995

The action spectra for UV-induced suppression of MLR and MECLR show that immunosuppression is mediated by DNA damage.

Ultraviolet-B (UVB, 280-320 nm) radiation can promote the induction of skin cancer by two mechanisms: damage of epidermal DNA and suppression of the immune system, allowing the developing tumor to escape immune surveillance. The mixed lymphocyte reaction (MLR) and the mixed epidermal cell lymphocyte reaction (MECLR) are commonly used methods to study the immunosuppressive effects of UVB radiation. To obtain a better understanding of the mechanism by which UVB radiation decreases the alloactivating capacity of in vitro-irradiated cells, action spectra for the MLR and MECLR were determined. Suspensions of peripheral blood mononuclear cells or epidermal cells were irradiated with monochromatic light of 254, 297, 302 or 312 nm and used as stimulator cells in the MLR or MECLR. Using dose-response curves for each wavelength, the action spectra were calculated. Both MLR and MECLR action spectra had a maximum at 254 nm and a relative sensitivity at 312 nm that was a thousand times lower than at 254 nm. Strikingly, the action spectra corresponded very closely to the action spectra that were found by Matsunaga et al. (Photochem. Photobiol. 54, 403-410, 1991) for the induction of thymine dimers and (6-4)photoproducts in irradiated calf thymus DNA solutions, strongly suggesting that the UV-induced abrogation of the MLR and MECLR responses is mediated by UV-induced DNA damage. Furthermore, the action spectra for the MLR and MECLR were similar, suggesting that they share a common mechanism for UV-induced suppression.

DNA Damage↗
PubMed1995

UVB-induced suppression of the mixed epidermal cell lymphocyte reaction is critically dependent on irradiance.

The mixed epidermal cell lymphocyte reaction (MECLR) is a commonly used method to study the effects of ultraviolet B (UVB) radiation on the skin immune system. In UVB experiments dosimetry is very important. The influence of irradiance on the MECLR was studied in vitro using Philips FS40 lamps with variable UV intensities. Irradiation of isolated epidermal cells with high irradiance impaired the alloactivating capacity more than irradiation with low irradiance. In vivo, the influence of long-term UVB exposure on the MECLR was studied by treating normal healthy volunteers with suberythemagenic doses of UVB thrice weekly during 4 weeks. The first set of experiments, using low irradiance Sylvania UV-21 F75/85 W lamps, resulted in a decrease of MECLR responses of 83.1%. In the second set of experiments performed a year later, employing an identical protocol except for the use of high irradiance Waldmann UV-21 F85/100 W lamps, an increase of MECLR responses of 99.7% was observed. Volunteers of both sets of experiments received equal doses of UVB. In conclusion, this study shows that in vitro UVB-induced suppression of the MECLR is critically dependent on irradiance and therefore might explain contradictory results described in the literature. The in vivo data suggest that, comparable to the in vitro experiments, irradiance may influence the effects of UVB irradiation in vivo. Further experiments should prove whether this is indeed the case.

Epidermal Cells↗
PubMed1994

IgG antibodies against an HLA antigen are associated with activated cytotoxic T cells against this antigen, IgM are not.

Pre-existing alloantibodies against the mismatched HLA-A and HLA-B antigens of the donor, when present in current sera, are believed to be detrimental to kidney graft survival. When these antibodies are present only in historical sera, their immunoglobulin class has reported to be important with respect to the expected graft survival, IgG antibodies being associated with poor graft prognosis and IgM with reasonable graft survival. In the present study, we have tested whether the immunoglobulin class of anti-HLA antibodies is reflected in the activation state of CTLs directed against these HLA antigens as measured by their in vitro resistance or sensitivity to CsA. The results indicate that the presence of IgG anti-HLA antibodies is associated with the presence of activated CTLs (CsA resistant), whereas in the case of IgM antibodies, mainly naive CTLs (CsA sensitive) are found. This observation may explain the different prognoses of historical positive crossmatches due to IgG versus IgM alloantibodies.

Cyclosporine↗