W A Allebes

Publications (15)56.94 Total impact

• Article: Adult metachromatic leukodystrophy treated by allo-SCT and a review of the literature.

  L D de Hosson, B P C van de Warrenburg, F W M B Preijers, N M A Blijlevens, B A van der Reijden, H P H Kremer, D J Lefeber, W A Allebes, H Al-Ali, D W Niederwieser, N P M Schaap, A V M B Schattenberg
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  ABSTRACT: Five patients with adult-onset metachromatic leukodystrophy (MLD) underwent allo-SCT. Conditioning was reduced in intensity and grafts were obtained from voluntary unrelated donors. All but one graft were depleted of T-lymphocytes. Patient age at transplantation varied from 18 to 29 (median, 27) years. Two patients rejected their graft and MLD progressed. The recipient of the unmanipulated graft converted to complete donor chimerism with normalization of arylsulphatase A (ARSA) levels. Despite ARSA normalization, he deteriorated. Another patient was a mixed chimera. Following escalated doses of donor lymphocyte infusions he converted to complete donor chimerism. His levels of ARSA correlated positively with the percentage of donor cells and MLD was not progressive. The fifth patient died after 35 days from complications associated with GVHD. We conclude that results of allo-SCT in symptomatic MLD patients are poor. However, allo-SCT may stop progression of MLD in selected patients.
  Bone marrow transplantation 11/2010; 46(8):1071-6. · 3.00 Impact Factor
• Article: Complete genomic sequence of a novel HLA-B allele, B*4456N.

  H J Tijssen, S W Driessen, K P van Houwelingen, W A Allebes, I Joosten
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  ABSTRACT: A novel allele, HLA-B*4456N, was identified upon cloning and sequencing of genomic DNA.
  Tissue Antigens 07/2009; 73(6):607-9. · 2.59 Impact Factor
• Article: Exon 2 sequence analysis of a novel HLA-DRB1 allele, DRB1*1460.

  H J Tijssen, J H G van den Dungen-Toet, K P van Houwelingen, W A Allebes, I Joosten
  Tissue Antigens 11/2006; 68(4):346-7. · 2.59 Impact Factor
• Article: Exon 2 sequence analysis of a novel HLA-DRB1 allele, DRB1*1520.

  H J Tijssen, S C van der Zeeuw-Hingrez, K P van Houwelingen, W A Allebes, I Joosten
  Tissue Antigens 11/2006; 68(4):347-8. · 2.59 Impact Factor
• Article: HLA-C mismatches induce strong cytotoxic T-cell reactivity in the presence of an additional DRB/DQB mismatch and affect NK cell-mediated alloreactivity.

  A van der Meer, W A Allebes, J Paardekooper, J Ruiter, I Joosten
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  ABSTRACT: The functional relevance of HLA-C mismatches in an alloresponse is still much debated, putting into doubt the relevance of matching for this antigen in selection of an allogeneic bone marrow donor. In addition to presenting peptides to T cells, HLA-C also functions as a ligand for killing inhibitory receptors (KIRs) on natural killer (NK) cells. In the current study we provide an in vitro basis to address the question of whether mismatches for this antigen are a risk factor for acute graft-versus-host disease (GVHD). By analysis of cytotoxic and helper T-lymphocyte precursor frequency (CTLp-f and HTLp-f) in 153 pairs, we are able to show that isolated HLA-C mismatches appear less immunogenic than do isolated HLA-A mismatches. Strikingly, the presence of an HLA-C mismatch next to a HLA-DRB or HLA-DQB mismatch leads to a synergistic increase in CTLp-f outcome. Moreover, we are the first to show that absence of a single inhibitory epitope as a result of an HLA-C mismatch can be sufficient to induce NK mediated alloreactivity, that is, kill and proliferate. We conclude that, in most cases, isolated HLA-C mismatches may be acceptable with respect to T-cell-mediated alloreactivity; however, the presence of a strong helper epitope (DR/DQ mismatch) appears sufficient to overcome the low immunogenicity of HLA-C. HLA-C mismatches that affect KIR epitopes, can induce NK mediated alloreactivity. This suggests that, in HLA-A-, -B-, -DR-, and -DQ-matched patients, NK cells may play a role in the induction and development of acute GVHD.
  Transplantation 10/2001; 72(5):923-9. · 4.00 Impact Factor
• Article: Cytotoxic T-lymphocyte precursor frequency (CTLp-f) as a tool for distinguishing permissible from non-permissible class I mismatches in T-cell-depleted allogeneic bone marrow transplantation.

  A van der Meer, I Joosten, A V Schattenberg, T J de Witte, W A Allebes
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  ABSTRACT: Matching for HLA has been the gold standard in bone marrow donor selection. But, with the ever increasing number of identified HLA alleles, it is becoming more difficult to find a fully HLA-identical donor other than a sibling. Retrospective analysis revealed that HLA mismatches do not necessarily give rise to acute graft-versus-host-disease (GVHD). However, we have no means of defining these 'permissible' mismatches before bone marrow transplantation (BMT). Thus, we set out to establish whether functional matching by means of helper and cytotoxic T-lymphocyte precursor frequency analysis (HTLp-f and CTLp-f respectively) can be applied to this end. Fifty-five recipient-donor pairs other than HLA-identical siblings, the recipient of which received a T-cell-depleted graft, were analysed by high-resolution HLA typing and/or HTLp-f/CTLp-f analysis. The predictive value of the CTLp-f assay for development of acute GVHD was confirmed. More importantly, our data indicate that the CTLp-f assay was able to discriminate permissible from non-permissible HLA-A, -B or -Cw mismatches, but not for DRB/DQB mismatches. The absolute number of alloreactive CTLs present in the graft correlated with the risk of acute GVHD. Although HTLp-f and CTLp-f together had a high negative predictive value, HTLp-f outcome by itself was not correlated with acute GVHD. As we have no evidence yet that HTLp-f or CTLp-f can identify permissible DRB/DQB mismatches, high-resolution matching for these antigens remains the best option. The combination of high-resolution DRB/DQB typing and the CTLp-f assay would enable the accurate prediction of the risk of acute GVHD while extending the pool of potential donors. Furthermore, it would enable adjustment of the number of T- cells in the graft accordingly to improve clinical outcome.
  British Journal of Haematology 12/2000; 111(2):685-94. · 4.94 Impact Factor
• Article: Helper and cytotoxic T cell precursor frequencies are not predictive for development of acute graft-versus-host disease after partially T cell-depleted HLA-identical sibling BMT.

  A van der Meer, W A Allebes, C E Voorter, E M van den Berg-Loonen, A V Schattenberg, T J de Witte, I Joosten
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  ABSTRACT: Despite the use of partially T cell-depleted grafts, 20% of the recipients of an HLA-identical sibling marrow graft develop aGVHD > or = II. This indicates that the current method for selecting a sibling donor, ie serological typing for HLA-A, B and DR, and a mixed lymphocyte culture (MLC) or molecular typing for HLA-DRB/DQB, is not predictive for aGVHD. In order to optimise our selection procedure, we retrospectively analysed patients who developed aGVHD > or = II by means of sequencing based typing for HLA-DPB and frequency analysis of alloreactive helper and cytotoxic T lymphocyte precursors (HTLp-f and CTLp-f). Patients who did not develop aGVHD or developed aGVHD grade I served as controls. Retrospective typing for HLA-DPB revealed only a single disparity in the group with aGVHD > or = II, indicating that mismatches for antigens other than HLA are the major cause of aGVHD in these patients. Furthermore, in our patient group, neither HTLp-f nor CTLp-f were predictive for development of aGVHD indicating that these assays in their current set-up are insufficiently sensitive to predict aGVHD in BMT with a partially T cell-depleted graft. We conclude, that HLA-identical siblings can be identified by means of serological typing for HLA-A and B and intermediate resolution molecular typing for DRB and DQB, but that for the prediction of aGVHD cellular tests with higher sensitivity and specificity as compared to the currently used HTLp-f and CTLp-f assays need to be developed.
  Bone Marrow Transplantation 01/1999; 22(11):1049-55. · 3.75 Impact Factor
• Article: DPB1*7601, a novel DPB1 variant in the Caucasoid population.

  E H Rozemuller, W A Allebes, E P van den Berg-Loonen, M Hidajat, A W van der Zwan, M G Tilanus, I Joosten
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  ABSTRACT: A new DPB1 allele has been identified in a Caucasoid individual, DPB1*7601. The sequence of the complete second exon has been confirmed by cloning and subsequent sequencing. This allele differs by one amino acid, at codon 36, from DPB1*1401, as indicated by SBT and PCR-SSP analysis. The amino-acid motif introduced by the change is shared by DPB1*0401 and some rare alleles. It remains unclear whether the change is due to interallelic microgen conversion or a single point mutation.
  Tissue Antigens 07/1998; 51(6):663-5. · 2.59 Impact Factor
• Article: A single [3H]thymidine-based limiting dilution analysis to determine HTLp and CTLp frequencies for bone marrow donor selection.

  A van der Meer, I Joosten, J Ruiter, W A Allebes
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  ABSTRACT: Histocompatibility between recipient and donor is a critical factor in allogeneic BMT which, to a large extent, determines the incidence of GVHD after BMT. Functional histocompatibility assays, such as the helper T lymphocyte precursor frequency assay (HTLp) and the cytotoxic T lymphocyte precursor frequency assay (CTLp), have proved to be helpful tools in facilitating donor selection procedures. However, a major drawback of these assays is that they are laborious and require large numbers of cells. We therefore adapted a [3H]thymidine-based assay, the 'JAM' test, as a read-out for CTLp frequencies, to replace the more cumbersome 51Cr-release assay. Furthermore, we applied an experimental setup that enables the assessment of HTLp and CTLp frequencies from a single limiting dilution assay to reduce the number of cells needed. The newly developed assay is relatively easy to perform and has the advantage that different subsets of T cells can be quantified in a single ongoing alloreaction. When the combined assay was applied in unrelated donor selection it proved to be a sensitive method that enables differentiation in suitability of distinct donors for a single patient. Therefore, the combined HTLp/CTLp assay appears to be a practical and sensitive method for identifying functional histocompatibility in related and unrelated donor/recipient combinations.
  Bone Marrow Transplantation 08/1997; 20(2):149-55. · 3.75 Impact Factor
• Article: Specificity and Ig class of preformed alloantibodies causing a positive crossmatch in renal transplantation. The implications for graft survival.

  G M ten Hoor, M Coopmans, W A Allebes
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  ABSTRACT: Sixty-five kidney transplantations performed across a non-current alloantibody-positive T cell crossmatch or an alloantibody-positive B cell crossmatch were studied retrospectively. The DTT crossmatch was used to discriminate between IgM and IgG donor-reactive antibodies. Subsequently the HLA specificity of donor-reactive IgG antibodies was determined in the MAILA assay. The first transplantations performed across a non-current positive T cell DTT crossmatch (IgG) were associated with poor graft survival, as only 5 of 11 (45%) transplants were functioning at 1 year. The HLA specificity of donor T cell reactive IgG antibodies appeared to determine the fate of the graft: only 2 of 7 (29%) patients with donor HLA class I-reactive antibodies had functioning grafts at 1 year, whereas all 3 patients with donor T cell-reactive antibodies, lacking HLA specificity, had functioning grafts. In 17 first transplantations, 15 grafts (88%) transplanted across an IgM-positive B cell crossmatch were functioning at 1 year. In 9 re-transplantations we found 6 grafts (67%) functioning at 1 year. B cell-reactive IgG antibodies, however, were associated with poor graft survival. In 7 first transplantations 2 grafts (29%) were functioning at 1 year, and in 17 re-transplantations 8 grafts (47%) were functioning at 1 year. For 19 patients the HLA specificity of donor B cell-reactive IgG antibodies was determined. Thirteen patients had HLA class II (-DR and/or -DQ)--specific antibodies; of these, 4 (31%) had a functioning graft at 1 year. Two of 3 (67%) patients with weak HLA class I--reactive antibodies and 2 of 3 (67%) patients with B cell--reactive IgG antibodies without HLA specificity had a functioning graft at 1 year. Although the number of cases analyzed is small, the following conclusions can be drawn: First, in general, the presence of donor HLA class I-, HLA-DR-, and HLA-DQ-reactive IgG antibodies is a contraindication to transplantation. However, under certain so-far-unknown conditions, transplantation across donor-reactive HLA specific IgG alloantibodies might be possible. Second, renal transplantation can be safely performed across B cell-reactive IgM antibodies. Third, donor-reactive IgG antibodies that do not recognize HLA do not seem to be harmful.
  Transplantation 09/1993; 56(2):298-304. · 4.00 Impact Factor
• Article: Phenotypic and functional changes of tumour cells from patients treated with monoclonal anti-idiotypic antibodies.

  W A Allebes, R Knops, R E Bontrop, N Otting, J Raemakers, C Haanen, P J Capel
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  ABSTRACT: In this paper data are presented indicating that immunotherapy with monoclonal anti-idiotypic antibodies (MoAb anti-id) can provoke different responses in the B-cell tumour concerned. With respect to the course of disease during and after immunotherapy, the in vitro findings may very well explain the in vivo observations in the two patients (D.E.F., B.O.R.) with B-cell chronic lymphocytic leukaemia (B-CLL) who were treated with MoAb anti-id. After initial tumour reduction, there was a recurrence of tumour cells with altered functional and phenotypic properties. In both cases the recurring tumour cells still expressed the same idiotype. In one patient (D.E.F.) the phenotypic changes (a surface Ig change from IgM, IgG, IgA, and IgD to weakly positive IgM and IgD) and functional changes (a 10-fold increase in [3H]thymidine uptake and a decreased idiotype secretion in vitro), together with the in vivo findings with respect to the course of disease--at relapse an impressive tumour regrowth rate with constant serum idiotype level--suggest that immunoselection might have taken place favouring the survival and relapse of a less mature, more aggressive tumour cell population with a lower idiotype expression. In the second patient (B.O.R.), the phenotypic changes (an isotype change from IgM and IgD to IgM with the loss of IgD, and a gradual decrease in expression of CD19 and CD24) and functional changes (a 10-fold increase of idiotype secretion in vitro), together with the in vivo finding that the serum idiotype level had increased 25-fold compared with the preimmunotherapy serum level with comparable tumour load, strongly suggest an immunotherapy-induced differentiation of the malignant B cell. We also describe an increased expression of CD74, detected by MoAb BoM22, on the recurring tumour cells of patient B.O.R., whereas the expression of HLA-DP, -DQ and -DR did not change. The significance of this finding is unclear.
  Scandinavian Journal of Immunology 12/1990; 32(5):441-9. · 2.23 Impact Factor
• Article: The development of non-responsiveness to immunotherapy with monoclonal anti-idiotypic antibodies in a patient with B-CLL.

  W A Allebes, F W Preijers, C Haanen, P J Capel
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  ABSTRACT: A patient having a B cell chronic lymphocytic leukaemia was treated with a monoclonal anti-idiotypic antibody (MoAb anti-id). Up to 24.5 g of MoAb anti-id has been administered to the patient over a period of 1 year without serious side effects. Despite a substantial amount of serum idiotype (id = 100 micrograms/ml) and a low expression of id on the tumour cells (+/- 6000 molecules per cell) clearance of serum id and a marked tumour reduction was obtained. Therapy resistance developed and coincided with a decreased clearance rate of circulating id-anti-id immune complexes and an increased modulation of cellular id expression, in vivo. This suggests that a decreased clearance rate of anti-id coated tumour cells provided more time for id modulation in vivo, resulting in therapy resistance. Therefore, the overall capacity of the natural effector system may have an important influence on the ultimate therapeutic effect of immunotherapy with MoAb anti-id. Although the partial remission obtained was not long-lasting, this study shows that MoAb anti-id therapy can be effective even when id expression on the tumour cells is low and a substantial amount of serum id is present.
  British Journal of Haematology 12/1988; 70(3):295-300. · 4.94 Impact Factor
• Article: Heterogeneous responses of B-cell tumours to anti-Ig and anti-idiotypic antibodies.

  W A Allebes, R H Wetzels, P J Capel
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  ABSTRACT: Anti-Ig antibodies can have two opposing effects on B-cell proliferation, resulting either in stimulation or inhibition. We have examined the proliferative response of 30 B-cell tumours to anti-Ig in the presence and absence of B-cell growth factor. Three reaction patterns were observed. In 12 cases a dose-dependent synergism between anti-Ig and B-cell growth factor was present in the induction of proliferation, in ten cases anti-Ig did not induce any response, and in eight cases anti-Ig suppressed the B-cell growth factor (BCGF)-induced proliferation. Similar responses to anti-Ig were found in the absence of BCGF. When these B-cell tumours were typed for expression of Ig isotypes, HLA class II antigens, several B-cell markers, activation markers, complement receptors, Fc receptors, cell size, and cell cycle phase, no correlation could be found with the proliferative response of these tumour B cells to anti-Ig. T cells or T-cell factors were not involved, because T-cell depletion did not change the tumour B-cell proliferative response to incubation with anti-Ig. The observed inhibition of proliferation did not correlate with the expression of Fc receptors, indicating the involvement of suppressor mechanisms other than the cross-linking of Fc receptors with surface immunoglobulins. Tumour B cells, for which monoclonal anti-idiotypic antibodies (MoAb anti-id) were available, responded to MoAb anti-id in the same way as they did to anti-Ig. In view of the treatment of B-cell malignancies with MoAb anti-id, the question of whether these responses in vitro correlate with in vivo clinical outcome of anti-id therapy is of interest. So far our data show that the proliferative response of B-cell tumours to anti-Ig or MoAb anti-id is heterogeneous and cannot be linked to phenotype, is T cell-independent, and is most likely an intrinsic property of the malignant cell.
  Scandinavian Journal of Immunology 08/1988; 28(1):95-103. · 2.23 Impact Factor
• Article: Characterization and tissue specificity of a monoclonal antibody against human uridine 5'-diphosphate-glucuronosyltransferase.

  W H Peters, W A Allebes, P L Jansen, L G Poels, P J Capel
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  ABSTRACT: A monoclonal antibody against human liver uridine 5'-diphosphate-glucuronosyltransferase (UDPGTase) was developed. Enzyme inhibition studies with this monoclonal antibody showed inhibition of human liver UDPGTase activity with bilirubin, 4-methylumbelliferone, and 4-nitrophenol as substrates. Testosterone, estrone, and phenolphthalein UDPGTase activity was not inhibited. The monoclonal antibody probably recognizes the uridine 5'-diphosphate-glucuronic acid binding site at 4-nitrophenol UDPGTase. Proteins with a molecular mass of 54,000 daltons were immunopurified from solubilized human liver using the monoclonal antibody as ligand coupled to Sepharose 4B beads. The distribution of UDPGTase isoforms in various human tissues was studied by immunofluorescence. The enzyme could be detected in liver, kidney, stomach, small intestine, colon, and skin. In liver, only hepatocytes contain UDPGTase. In kidney, the enzyme was localized exclusively in proximal tubuli and in stomach in epithelial mucous cells. In small intestinal epithelium, maximal fluorescence was seen at the villous tip. In colon, all lining epithelial cells were stained. In colon polyps, staining for UDPGTase was clearly decreased, and in colon carcinoma it was undetectable. In skin, the stratum corneum was intensely stained, whereas the stratum basale showed no fluorescence.
  Gastroenterology 08/1987; 93(1):162-9. · 11.68 Impact Factor
• Article: Treatment of chronic lymphocytic leukaemia with monoclonal anti-idiotypic antibody.

  P J Capel, F W Preijers, W A Allebes, C Haanen
  The Netherlands Journal of Medicine 02/1985; 28(3):112-8. · 2.07 Impact Factor