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Biomedical subjects

Frans H J Claas

Publications and source records attributed to Frans H J Claas.

At least 19 recordsLinked to original sources
PubMed2006

A highly efficient living donor kidney exchange program for both blood type and crossmatch incompatible donor-recipient combinations.

BACKGROUND: Lack of deceased donors for kidney transplant patients in the Netherlands encouraged alternative options to expand the living donor pool for recipients who have a willing donor but cannot donate directly because of a positive crossmatch or ABO blood type incompatibility. A national donor kidney exchange was considered as a possible solution. METHODS: From January 2004 until June 2006, 146 couples from seven kidney transplantation centers were enrolled and participated in 10 match procedures. The Dutch Transplant Foundation was responsible for the allocation and the National Reference Laboratory for Histocompatibility in Leiden performed all the serological crossmatches. RESULTS: For 72 out of the 146 (49%) donor-recipient combinations, a match was found. The success rate in the positive crossmatch group was significantly (P = 0.0015) higher than in the ABO-incompatible group (44/69 vs. 28/77); median panel reactive antibodies of the matched recipients in the positive crossmatch group was 38% (0-100) and in the ABO-incompatible group 0% (0-27; P < 0.001). We were least successful for ABO blood type incompatible pairs with blood type O recipients, but for 9/53 (17%) there were possibilities. These nine blood type incompatible pairs were coupled to nine positive crossmatch pairs, which reflects the efficiency of combining the two categories of donor-recipient combinations into one program. CONCLUSION: The donor kidney exchange program in the Netherlands, in which all seven kidney transplantation centers participated, proved to be a successful program to expand the number of living donor kidney transplantations.

ABO Blood-Group System↗
PubMed2006

Stable T-cell reactivity after successful tapering of azathioprine in HLA-identical living-related kidney transplant recipients despite minor histocompatibility antigen mismatches.

BACKGROUND: Human leukocyte antigen (HLA)-identical living-related (LR) kidney transplant recipients often receive the standard regimen of immunosuppression. We wondered whether these patients should be exposed to the side effects of these drugs any longer. Safe tapering of immunosuppression should not result in rejection and high donor-directed T-cell responses. In the present study, we investigated the effect of tapering azathioprine (AZA) on T-cell reactivity. METHODS: Fifteen HLA-identical LR kidney transplant recipients receiving a median of 150 mg/day AZA and 5-10 mg/day prednisone were tapered to a median of 50 mg/day AZA. Donor-, third-party and tetanus toxoid (TET)-reactivity were determined in interferon (IFN)-gamma and interleukin (IL)-13 Elispot assays, which reflect the T-helper (Th)1 and T-helper (Th)2 response. RESULTS: After the tapering of AZA, none of the patients developed acute rejection and the renal function remained stable, even at 1-year follow-up. The frequency of donor-specific IFN-gamma and IL-13 producing cells (pc) was low. Tapering of AZA did not influence the frequency of both IFN-gamma and IL-13 pc. Also, the reactivity against third-party cells and TET remained unchanged. CONCLUSIONS: The AZA-dose can be safely reduced in recipients of an HLA-identical LR kidney transplant without affecting kidney function and without increasing T-cell responses directed against donor or other antigens.

Azathioprine↗
PubMed2006

High-resolution analysis of HLA class I alterations in colorectal cancer.

BACKGROUND: Previous studies indicate that alterations in Human Leukocyte Antigen (HLA) class I expression are frequent in colorectal tumors. This would suggest serious limitations for immunotherapy-based strategies involving T-cell recognition. Distinct patterns of HLA surface expression might conceal different immune escape mechanisms employed by the tumors and are worth further study. METHOD: We applied four-color multiparameter flow cytometry (FCM), using a large panel of alloantigen-specific anti-HLA-A and -B monoclonal antibodies, to study membranous expression of individual HLA alleles in freshly isolated colorectal cancer cell suspensions from 21 patients. RESULTS: Alterations in HLA class I phenotype were observed in 8 (38%) of the 21 tumors and comprised loss of a single A or B alleles in 4 cases, and loss of all four A and B alleles in the other 4 cases. Seven of these 8 tumors were located on the right side of the colon, and those showing loss of both HLA-A and -B membranous expression were all of the MSI-H phenotype. CONCLUSION: FCM allows the discrimination of complex phenotypes related to the expression of HLA class I. The different patterns of HLA class I expression might underlie different tumor behavior and influence the success rate of immunotherapy.

Aged↗
PubMed2006

The ratio of interferon-gamma and interleukin-10 producing donor-specific cells as an in vitro monitoring tool for renal transplant patients.

If in vitro tools can be used to predict which renal transplant patients are at risk for rejection and which patients are more predisposed to tolerance, the immunosuppressive regimen can be adjusted to prevent rejection before it becomes clinically apparent or, in case of a tolerant patient, medication can be reduced or even stopped. Peripheral blood mononuclear cells (PBMC) of patients with persistent stable graft function and of patients with (biopsy-confirmed) acute rejection were stimulated with donor cells and tested with Elispot analysis. A significantly higher number of donor-specific interferon (IFN)-gamma producing cells were found in patients with rejection, as determined with Elispot analysis. Furthermore, a trend towards a higher number of interleukin (IL)-10 producing cells was found in patients with stable graft function. The ratio of IFN-gamma/IL-10 producing cells showed to be the best tool to discriminate between nonrejecting patients and rejecting patients.

Adult↗
PubMed2006

Rapid assessment of the antigenic integrity of tetrameric HLA complexes by human monoclonal HLA antibodies.

The ability of tetrameric major histocompatibility complex (MHC) class I-peptide complexes (tetramers) to detect antigen-specific T lymphocyte responses has yielded significant information about the generation of in vivo immunity in numerous antigenic systems. Here we present a novel method for rapid validation of tetrameric HLA molecules based on the presence of allodeterminants. Human monoclonal antibodies (mAbs) recognizing polymorphic determinants on HLA class I were immobilized on polystyrene microparticles and used to probe the structural integrity of tetrameric HLA class I molecules by flow cytometry. A total of 22 tetramers, based on HLA-A1, A2, A3, A24, B7 and B8 were reactive with their counterpart mAbs, thus confirming their antigenic integrity. A positive outcome of this mAb test ensures that tetrameric HLA class I can be used with greater confidence in subsequent functional assays.

Antibodies, Monoclonal↗
PubMed2006

Functional CD8+ T cells infiltrate into nonsmall cell lung carcinoma.

Infiltration of CD3(+)CD8(+) cytotoxic T cells was analyzed by multiparameter confocal laser microscopy in a panel of 16 randomly selected stage I nonsmall cell lung carcinomas. T-cell infiltration was observed in the stroma (range 57-2,093 T cells/mm(2)) but also in the tumor epithelium (range 21-892 T cells/mm(2)) and showed wide variation between individual tumors. Interestingly, a significantly higher percentage of CD3(+)CD8(+) T cells was detected in the tumor epithelium compared to the stroma illustrating that cytotoxic T cells may preferentially migrate into tumor epithelium. Aberrant HLA class I antigen expression was observed in 69% of the nonsmall-cell lung carcinoma (NSCLC) tumors. One tumor of a squamous cell lung carcinoma patient with the highest number of tumor infiltrating CD3(+) and CD3(+)CD8(+) cells was studied in detail and the majority (90%) of these cells were shown to be functionally activated granzyme B-positive cytotoxic T cells. DNA oligotyping of a lung carcinoma cell line established from this tumor revealed loss of one HLA haplotype corresponding with a translocation involving chromosome 6, as observed by COBRA-FISH. HLA class I-restricted tumor specific T cells could be isolated from PBMC. One further characterized cytotoxic CD8(+) T cell clone, that released TNF-alpha, IFN-gamma, and granzyme B upon co-incubation with the autologous tumor cells, was shown to be restricted by the remaining HLA-A11 allele, which was also shown to be expressed in the tumor tissue. Our data indicate that, despite HLA-haplotype loss a vigorous antitumor immune response mediated by CD8(+ )T-cells can be present in NSCLC offering possibilities for specific immunotherapy.

CD8-Positive T-Lymphocytes↗
PubMed2006

Differential immunogenicity of HLA class I alloantigens for the humoral versus the cellular immune response: "towards tailor-made HLA mismatching".

The immunogenicity of an individual human leukocyte antigen (HLA) class I mismatch is different for the cellular and the humoral alloimmune responses. The consequence is that the same antigen can induce a strong antibody response and no cytotoxic T lymphocyte reactivity, but the reverse can occur also. Exact knowledge of the immunogenicity of an HLA mismatch for an individual patient can lead to a strategy of tailor-made HLA mismatching if no HLA identical donor is available. Depending on the clinical situation, one should select a donor with HLA mismatches according to the humoral or cellular mismatch algorithm.

Antibody Formation↗
PubMed2006

No in vitro evidence for a decreased alloreactivity toward noninherited maternal HLA antigens in healthy individuals.

Pre- and/or perinatal exposure to noninherited maternal HLA antigens (NIMA) is associated with a decreased HLA antibody formation against the NIMA and a significantly better graft survival of kidney grafts from siblings or those from unrelated donors who were mismatched for the NIMA haplotype compared with the NIPA (noninherited paternal HLA antigens) haplotype later in life. These observations suggest that some form of immunological tolerance against NIMA is induced. We analyzed the in vitro T cell reactivity of healthy individuals toward their parents and/or siblings expressing the NIMA or NIPA haplotype to explore whether the alloimmune response to NIMA has distinct characteristics compared with NIPA. No differences were detected by mixed lymphocyte reactions (MLR) and supernatants taken from the MLR showed no differences in IFN-gamma and IL-10 production. Additionally, no differences were found with IFN-gamma and IL-10 Elispot analyses. Phenotypic analysis revealed no selective increase in the number of CD3-CD8dim cells (thought to be a NK-like regulator cell) and the number of CD4+CD25+CD152+ cells (naturally occurring regulatory T cells) after stimulation with NIMA-expressing cells when compared with NIPA-expressing cells. In conclusion, no evidence of an influence of a NIMA effect on the cellular level was found in healthy individuals with "standard" immunological techniques.

Enzyme-Linked Immunosorbent Assay↗
PubMed2006

The influence of inherited and noninherited parental antigens on outcome after transplantation.

Contact between the immune systems of mother and child during pregnancy has an impact on transplantation later in life. Exposure to inherited paternal human leukocyte antigens (HLA) (IPA) and the noninherited maternal HLA antigens (NIMA) can lead to either immunization or tolerization. Exposure to IPA seems to have a more immunizing effect as the mature immune system of a mother can form anti-HLA antibodies against the foreign paternal HLA molecules. On the other hand, exposure of a child to the NIMA antigens during pregnancy may lead to NIMA-specific tolerance. This review provides an overview of the current knowledge on the impact of this fetal-maternal interaction on the alloimmune response and clinical transplantation.

Animals↗
PubMed2006

HLA Class I and II genotype in uveal melanoma: relation to occurrence and prognosis.

PURPOSE: To assess whether human leukocyte antigen class I and class II alleles confer susceptibility to uveal melanoma or are related to specific clinical or tumor characteristics and survival. METHODS: Between 1990 and 2004, 235 consecutive Dutch patients with diagnoses of primary uveal melanoma were typed for HLA class I and II, either by complement-dependent cytotoxicity test or by DNA-based technique. Allele frequencies were compared with those of a control group that consisted of 2440 healthy Dutch blood donors. In addition, allele frequencies of 138 patients with uveal melanoma, who underwent enucleation as primary treatment, were compared for tumor characteristics and survival. RESULTS: With regard to tumor characteristics, correlations between HLA-DR13 and tumor size, HLA-B35 and spindle cell type, and HLA-B60 and ciliary body involvement were observed before correction for the number of alleles tested. Correlation was found between the presence of HLA-B44 and decreased survival. We did not find any allele that correlated with susceptibility to uveal melanoma after correction for the number of comparisons between patients and controls. CONCLUSIONS: This study shows that HLA class I and II antigens do not contribute to an increased genetic susceptibility to uveal melanoma. This does not exclude an important role for HLA antigens in immune surveillance against uveal melanoma and their metastases.

Adult↗
PubMed2005

Impact of peptides on the recognition of HLA class I molecules by human HLA antibodies.

MHC class I molecules expressed on cell surfaces are composed of H chain, beta2-microglobulin and any of a vast array of peptides. The role of peptide in the recognition of HLA class I by serum HLA Abs is unknown. In this study, the solid-phase assay of a series (n = 11) of HLA-A2-reactive, pregnancy-induced, human mAbs on a panel (n = 12) of recombinant monomeric HLA-A2 molecules, each containing a single peptide, revealed peptide selectivity of the mAbs. The flow cytometry membrane staining intensities on the HLA-A2-transduced cell line K562, caused by these mAbs, correlated with the number of monomer species detected by the mAbs. Flow cytometry staining on HLA-A2-bearing cell lines of a variety of lineages was indicative of tissue selectivity of these HLA-A2 mAbs. This tissue selectivity suggests that the deleterious effect on allografts is confined to alloantibodies recognizing only HLA class I loaded with peptides that are derived from tissue-specific and household proteins. Since Abs that are only reactive with HLA loaded with irrelevant peptides are expected to be harmless toward allografts, the practice of HLA Ab determination on lymphocyte-derived HLA deserves reconsideration.

Antibodies, Monoclonal↗
PubMed2005

Exclusive characteristics of graft survival and risk factors in recipients with immunoglobulin A nephropathy: a retrospective analysis of registry data.

BACKGROUND: Some studies have claimed that patients with immunoglobulin A (IgA) nephropathy have better graft survival than other renal graft recipients, whereas others have rejected this statement. We have addressed this paradox in the present study. METHODS: In all, 1,207 patients with IgA nephropathy who received a primary cadaveric renal graft from 1990 to 2002 were identified in the Eurotransplant database. For comparison, we analyzed 7,935 patients with nonglomerular diseases. Death-censored graft survival was calculated using Kaplan Meier estimates and a multivariable Cox regression analysis was used for risk calculations. RESULTS: Death-censored graft survival was superior in patients with IgA nephropathy in the first period after transplantation. After 3 years posttransplant, however, there was an accelerated decline in graft survival in recipients with IgA nephropathy. The fully adjusted risk of graft loss in the first year was increased by 40% in the control group compared to IgA nephropathy (hazard ratio [HR] 1.40, 95% CI 1.12-1.75), whereas the risk was significantly lower in the control group after the first year posttransplant (HR 0.75, 95% CI 0.63-0.88). Cold ischemia time, immunization and HLA-DR mismatch were risk factors for graft loss in the control group but not for IgA nephropathy, whereas HLA-AB mismatch was an independent risk factor, exclusively for the IgA nephropathy group. CONCLUSIONS: Recipients with IgA nephropathy have better 1-year graft survival, presumably due to favorable immunological behavior. This benefit was however abolished in the long-term by increased graft loss with time. Studies are needed to explain the difference in graft survival and the reason why different risk factors are involved in graft failure.

Adolescent↗
PubMed2005

Allogeneic MHC class I molecules with numerous sequence differences do not elicit a CTL response.

CD8+ T cell-mediated alloreactivity is generally believed to involve recognition of the alpha1/alpha2 domains of donor-type class I MHC molecules as well as the peptides they bind. Using the CTLp assay outcome as a parameter for the induction of alloreactivity, we have retrospectively surveyed 80 haematopoietic stem cell donor/patient pairs that feature a range of allelic differences at single HLA-A, -B, and -C loci in an attempt to probe the predictive value of such mismatches. In contrast to the expectation that greater degree of allelic disparity would lead to more alloreactivity, we found that in a substantial number of cases, class I MHC molecules with numerous sequence differences did not elicit an allogeneic CTL response. We propose that in generating a T cell repertoire with a sufficiently narrow responsive for self-MHC, positive thymic selection limits the capacity to recognize allogeneic MHC molecules whose structure and sequence have diverged extensively. These findings are important for donor and patient MHC matching strategies and our understanding of T cell-MHC interaction after haematopoietic stem cell transplantation.

Amino Acid Substitution↗
PubMed2005

Alloreactivity against repeated HLA mismatches of sequential islet grafts transplanted in non-uremic type 1 diabetes patients.

BACKGROUND: Islet transplantation can restore insulin production in type 1 diabetes patients. However, survival of the islet allografts will face rejection or recurrence of autoimmunity or a combination of both. In a study on islet-after-kidney transplants, we previously reported that islet cell recipients presented low T-cell alloresponses for HLA mismatches that were shared by the islet cell graft and the prior kidney graft, that is, repeated mismatch, while vigorous responses were measured against novel HLA mismatches. METHODS: We now investigated T-cell alloreactivity to repeated HLA-mismatches in three non-uremic type 1 diabetic patients each receiving three sequential islet cell implants. RESULTS: These islet-after-islet recipients patients exhibited low or absent responses to repeated mismatches to the first graft which was accompanied by sustained graft function, and reduced responsiveness towards subsequent grafts. In one patient, T-cell responses towards these mismatches were noticed following new mismatches in subsequent grafts, with loss of graft function. CONCLUSION: These case reports further support the view that subsequent islet implantations can reduce alloreactivity for repeated HLA mismatches. They demonstrate the usefulness of monitoring T-cell reactivity against islet allografts to correlate immune function with graft survival and to identify conditions for preservation of beta-cell function.

Antilymphocyte Serum↗
PubMed2005

Single-antigen-expressing cell lines are excellent tools for detecting human leukocyte antigen-C-reactive antibodies in kidney transplant recipients.

BACKGROUND: Human leukocyte antigen (HLA)-C is expressed on nucleated cells and platelets in lower levels than HLA-A,B, and its antigens are in linkage disequilibrium with HLA-B antigens. Therefore, HLA-C antibody detection is difficult. The authors questioned whether HLA-C could serve as a target in clinical kidney transplantation using a newly developed assay. METHODS: Flow cytometry was performed with sera from patients (n=34) awaiting a kidney retransplant using nine cell lines expressing a single HLA-C antigen (single-antigen lines [SAL]). RESULTS: The SAL were validated with HLA-C-specific alloantisera and human monoclonal antibodies against HLA-A, -B, and -C. The results were in agreement with the specificities previously reported. Exceptions, because of new HLA-C specificities used here, could be explained by epitope sharing between the antigens. With respect to patient sera, 15 of the 34 patients tested (44%) showed serum reactivity toward one or more HLA-C SAL. CONCLUSIONS: In contrast to peripheral blood lymphocytes, SAL are excellent targets for detecting HLA-C-reactive alloantibodies by flow cytometry. This preliminary analysis revealed that HLA-C-reactive antibodies are frequently present in sera of retransplant patients, serving as possible targets in clinical transplantation.

Antibodies↗
PubMed2005

Differential immunogenicity of HLA mismatches in clinical transplantation.

Although HLA matching is beneficial in clinical transplantation, it is not feasible to select a completely HLA matched donor for every potential recipient because of the enormous polymorphism of the HLA system. As a consequence, the majority of the recipients will be transplanted with a mismatched donor organ or hematopoietic stem cell transplant. For this large group of patients it is important to take advantage of the differential immunogenicity of HLA mismatches and to select for them a donor with HLA mismatches of low immunogenicity, the so-called acceptable mismatches. The differential immunogenicity of HLA mismatches can be determined by either retrospective analysis of graft survival data or by in vitro assays measuring T-cell and B-cell alloreactivity. A recently developed computer algorithm (HLAMatchmaker) can be instrumental in selecting donors with HLA mismatches, which do not lead to alloantibody formation. The theoretical background and practical implications of this acceptable mismatch approach are discussed.

Algorithms↗
PubMed2005

The single antigen expressing lines (SALs) concept: an excellent tool for screening for HLA-specific antibodies.

Definition of the antibody specificity in the serum of patients waiting for a renal transplant or in need for platelet transfusion is a crucial step for finding adequate donors. Confounding factors are the complexity of the serum antibodies and the expression of several, up to six, different human leukocyte antigens (HLA) on peripheral blood lymphocytes used as target cells in the antibody screening. Single antigen-expressing (SAL) cell lines were generated by transfecting human major histocompatibility complex (MHC) class I sequences into K562, an erythroleukemia-derived cell line lacking MHC class I and II expression. Thirty-seven different SALs have been generated so far. In this study, we present the validation of 16 of those SALs by flow cytometry against a panel of 84 human HLA-specific monoclonal antibodies (30 HLA-A [8 IgG/22 IgM], 45 HLA-B [18 IgG/27 IgM], 6 HLA-A, B [3 IgG/3 IgM], and 3 HLA-C [all IgM]) developed in our laboratory. The SALs proved to be suitable tools to determine acceptable mismatches for highly sensitized patients. This concept of transfecting target sequences in immortalized cell lines opens up new avenues in the definition of serum and cellular reactivity for sensitized patients awaiting a suitable organ or blood component.

Antibodies↗