Biomedical subjects
Publications and source records attributed to F H J Claas.
International collaboration is essential for the optimal selection of unrelated hematopoietic stem cell donors. This review focuses on the benefit of a joint worldwide donor file called Bone Marrow Donors Worldwide and the experience of the Europdonor Foundation in selecting strategies to identify the best human leukocyte antigen-matched donor in the shortest time.
During pregnancy several maternal and fetal mechanisms are established to prevent a destructive immune response against the allogeneic fetus. Despite these mechanisms, fetus specific T-cells persist throughout gestation but little is known about the regulation of these T-cells. Recently, CD4(+)CD25(+) regulatory T-cells have been identified in human decidua. Human decidua forms the maternal part of the fetal-maternal interface and is subdivided in two distinct regions: the decidua (d.) basalis and the decidua (d.) parietalis. The aim of this study was to determine the distribution of specific T-cell subsets in d. basalis and d. parietalis in early and term pregnancy, with a special emphasis on the presence of CD4(+)CD25(bright) (regulatory) T-cells and CD8(+)CD28(-) (suppressor) T-cells. In addition, we compared phenotypic characteristics of decidua derived T-cell subsets with maternal peripheral blood (mPBL) T-cells and T-cells from non-pregnant controls. We identified significantly higher percentages of CD4(+)CD25(bright) and CD8(+)CD28(-) T-cells in decidua compared to peripheral blood suggesting an important role for these T-cell subsets locally at the fetal-maternal interface. The major differences in T-cell subset distribution and the presence of additional phenotypic differences between T-cells in d. basalis, d. parietalis and mPBL may reflect specific immunomodulatory functions of these T-cell subsets at these different sites during pregnancy.
BACKGROUND: Strategies to decrease the wait time for kidney transplantation include the use of living donor kidneys. However, it is not always possible to donate directly, due to ABO blood type incompatibility or a positive crossmatch. Therefore, other options were explored, including a program for living donor kidney exchange. METHODS: All Dutch kidney transplantation centers agreed on a common donor kidney exchange protocol. The Dutch Transplantation Foundation is responsible for the allocation, crossmatches are centrally performed, and exchanges take place on an anonymous basis. Donors travel to the recipient centers. Surgical procedures are simultaneously scheduled. RESULTS: From January 2004, we registered in total 116 combinations consisting of blood type-incompatible pairs (n = 62) and positive crossmatch pairs (n = 54). In eight match procedures we created 58 new donor-recipient combinations with negative crossmatches, including six triplets and 20 doublets. It proved to be significantly (P = .0014) less difficult to find a solution for the crossmatch-positive combinations than for the blood type-incompatible combinations (67% vs 35%). CONCLUSION: The Dutch national living donor kidney exchange program resulted in a 50% success rate. Combining blood type-incompatible and crossmatch-positive donor-recipient pairs in one program is a realistic option for all blood type combinations.
PURPOSE: The molecules of the HLA class I and II molecules as well as the MHC class I chain-related gene A (MICA), a polymorphic and stress-induced cell surface molecule, are involved in T-cell and natural killer-cell (NK-cell) mediated immune responses. In this study we looked for any genetic susceptibility contributed by HLA class I, class II, or MICA genes with regard to the development of uveal melanoma. METHODS: Between 1998 and 2001, 159 uveal melanoma patients were typed for HLA class I and II, and 168 uveal melanoma patients were evaluated for MICA by microsatellite typing. The HLA antigen and MICA allele frequencies were compared with control groups of, respectively, 2,440 and 247 healthy Dutch individuals. RESULTS: HLA class I, HLA class II, and MICA gene frequencies in uveal melanoma patients and healthy Dutch controls showed no significant deviations after correction for the number of comparisons. CONCLUSIONS: We conclude that there is no genetic susceptibility or increased risk attributed to any HLA class I, class II, and MICA polymorphism with regard to the development of uveal melanoma.
Solid organ transplant patients have an increased risk of cutaneous squamous cell carcinomas compared to the immunocompetent population, and often develop multiple and sometimes aggressive tumours. There are few published studies or reviews, which provide guidance to the clinician in the management of these patients. In the prevention of skin cancer in organ transplant patients, patient education about the harmful effects of ultraviolet radiation, sun protection, and the early recognition of (pre)malignant skin lesions should be emphasised. Furthermore, close follow-up by a dermatologist and treatment of (pre)malignant lesions in an early stage are necessary. Chemoprevention of skin cancer can be achieved through systemic retinoids. Reduction of the dose of immunosuppressive agents can be considered. Excision is the first treatment of choice for squamous cell and basal cell carcinomas. In selected rumours curettage and electrodessication can be performed.
Many patients do not reach haematopoietic stem cell transplantation. Shortage of unrelated donors (UDs) is still seen as the main cause. However, with a worldwide UD pool containing more than 8 million donors, it is possible that other impediments are becoming more important. We analysed 549 UD searches for Dutch patients, performed between 1987 and 2000, in order to find the reasons for failure or success to reach transplantation. Between 1996 and 2000, 59% of the patients of Northwest European origin received a graft from an UD with a median time span of 4.4 months from the start of the search. In all, 11% of the patients lacked a compatible donor, while 30% became medically unfit for transplantation. This is in contrast to the patients of non-Northwest European origin for whom UD shortage is still the most important impediment; only 32% were transplanted while 50% lacked a compatible donor. We conclude that the shortage of donors is no longer the biggest constraint in unrelated stem cell transplantation for patients of Northwest European origin. It may be more effective to optimize the chance on transplantation by making the search process more efficient.
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Confrontation of the unborn child immune system with the noninherited maternal antigens (NIMAs) has a lifelong modulating impact on the immune response of the child against the NIMAs. In this review we summarize the clinical evidence for the existence of the NIMA effect, discuss the possible cellular and molecular basis of the phenomenon, and outline the necessity of further clinical research.
The role of alloreactive NK cells in haematopoietic stem-cell transplantation is a controversial topic. Different studies come up with different conclusions. This is mainly due to heterogeneous patient populations, differences in the sources of haematopoietic stem cells and various conditioning regimens. International collaboration is essential to reveal in which situation NK cell alloreactivity plays a role and, if so, whether it is beneficial or detrimental for patient survival.
BACKGROUND: The results of living-donor (LD) renal transplantations are better than those of postmortem-donor (PMD) transplantations. To investigate whether this can be explained by a more favorable patient selection procedure in the LD population, we performed a Cox proportional hazards analysis including variables with a known influence on graft survival. METHODS: All patients who underwent transplantations between January 1981 and July 2000 were included in the analysis (n=1,124, 2.6% missing values). There were 243 LD transplantations (including 30 unrelated) and 881 PMD transplantations. The other variables included were the following: donor and recipient age and gender, recipient original disease, race, current smoking habit, cardiovascular disease, body weight, peak and current panel reactive antibody, number of preceding transplants and type and duration of renal replacement therapy, and time since failure of native kidneys. In addition, the number of human leukocyte antigen identical combinations, first and second warm and cold ischemia periods, left or right kidney and fossa, donor kidney anatomy, donor serum creatinine and proteinuria, and transplantation year were included. RESULTS: In a multivariate model, donor origin (PMD vs. LD) significantly influenced the graft failure risk censored for death independently of any of the other risk factors (P=0.0303, relative risk=1.75). There was no time interaction. When the variable cold ischemia time was excluded in the same model, the significance of the influence of donor origin on the graft failure risk increased considerably, whereas the magnitude of the influence was comparable (P=0.0004, relative risk=1.92). The influence of all other variables on the graft failure risk was unaffected when the cold ischemia period was excluded. The exclusion of none of the other variables resulted in a comparable effect. Donor origin did not influence the death risk. CONCLUSION: The superior results of LD versus PMD transplantations can be partly explained by the dichotomy in the cold ischemia period in these populations (selection). However, after adjustment for cold ischemia periods, the influence of donor origin still remained significant, independent of any of the variables introduced. This superiority is possibly caused by factors inherent to the transplanted organ itself, for example, the absence of brain death and cardiovascular instability of the donor before nephrectomy.
BACKGROUND: HLA typing and matching have been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations were performed by a single surgeon in a single center between 1976 and 1996. Population genetic and other statistical analyses were performed. Simulation studies assessed the effects of HLA-DR mistypings on analytical results. RESULTS: Mono- and multivariate analyses identified retransplantation, degree of vascularization, HLA-AB and -DR match grades, endothelial cell count, graft size, recipient gender, storage method and panel-reactive antibodies as significantly influencing the survival of corneal transplants. Simulation studies showed that the beneficial effect of HLA-DR matching is abrogated by HLA-DR mistypings. CONCLUSIONS: Corneal transplant recipients have a normal immune response to HLA incompatibilities. Demonstration of that fact requires accurate HLA typings.
Human leukocyte antigen (HLA) incompatibilities are the most important immunological barriers to bone marrow transplant success when using unrelated donors. Until recently, standards for donor selection included serological methods for HLA class I antigens and DNA-based typing for HLA class II alleles. In our center cytotoxic T-lymphocyte precursor (CTLp) assays have been an integrated part of the search selection procedure as well. More recently, DNA-based typing for HLA class I became available. This allowed us to determine the correlation of CTLp frequencies directed against incompatibilities at the HLA-A, -B, and -C locus in 211 donor-recipient pairs. HLA class I incompatibilities are significantly (p < 0.001) associated with high CTLp frequencies. Exceptions did occur, high CTLp frequencies are seen in 14% of the HLA-A, -B, and -C allele matched pairs, whereas in 7% of the pairs mismatched for HLA-A or -B a low CTLp frequency occurred. The successful outcome of transplants performed in the latter cases suggest that the CTLp test can be used as a tool to detect permissible mismatches when no fully matched donor is available. The influence of HLA-C mismatches on the CTLp outcome was less clear. Although in the majority of mismatched pairs (64%) the CTLp frequency was high, in 36% of the pairs the CTLp frequency was low. Analysis of HLA amino acid sequences was performed on the HLA-C allele mismatched group. An amino acid difference was always found at five polymorphic positions 97, 99, 113, 114, and 116 situated at the peptide binding groove in the high CTLp frequency group, whereas in the low CTLp frequency group this was observed in only 9 of 17 combinations (p < 0.001). However, this is mainly due to Cw*0303-0304 mismatches. In conclusion, although there is a highly significant correlation between the outcome of the CTLp frequency test and HLA allele class I typing, exceptions occur. It is unclear whether they are all clinically relevant but they certainly provide additional insight in allograft recognition.