12 results on '"Lardy, Neubury M."'
Search Results
2. Antibodies against ARHGDIB are associated with long-term kidney graft loss
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Kamburova, Elena G., Gruijters, Maartje L., Kardol-Hoefnagel, Tineke, Wisse, Bram W., Joosten, Irma, Allebes, Wil A., van der Meer, Arnold, Hilbrands, Luuk B., Baas, Marije C., Spierings, Eric, Hack, Cornelis E., van Reekum, Franka E., van Zuilen, Arjan D., Verhaar, Marianne C., Bots, Michiel L., Drop, Adriaan C.A.D., Plaisier, Loes, Melchers, Rowena C.A., Seelen, Marc A.J., Sanders, Jan Stephan, Hepkema, Bouke G., Lambeck, Annechien J.A., Bungener, Laura B., Roozendaal, Caroline, Tilanus, Marcel G.J., Voorter, Christina E., Wieten, Lotte, van Duijnhoven, Elly M., Gelens, Mariëlle A.C.J., Christiaans, Maarten H.L., van Ittersum, Frans J., Nurmohamed, Shaikh A., Lardy, Neubury M., Swelsen, Wendy, van der Pant, Karlijn A.M.I., van der Weerd, Neelke C., ten Berge, Ineke J.M., Hoitsma, Andries, van der Boog, Paul J.M., de Fijter, Johan W., Betjes, Michiel G.H., Heidt, Sebastiaan, Roelen, Dave L., Claas, Frans H., Bemelman, Frederike J., and Otten, Henny G.
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- 2019
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3. Determining the extent of maternal-foetal chimerism in cord blood
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Opstelten, Rianne, Slot, Manon C., Lardy, Neubury M., Lankester, Arjan C., Mulder, Arend, Claas, Frans H. J., van Rood, Jon J., and Amsen, Derk
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- 2019
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4. Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients
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Heidt, Sebastiaan, Haasnoot, Geert W., Witvliet, Marian D., van der Linden-van Oevelen, Marissa J.H., Kamburova, Elena G., Wisse, Bram W., Joosten, Irma, Allebes, Wil A., van der Meer, Arnold, Hilbrands, Luuk B., Baas, Marije C., Spierings, Eric, Hack, Cornelis E., van Reekum, Franka E., van Zuilen, Arjan D., Verhaar, Marianne C., Bots, Michiel L., Drop, Adriaan C.A.D., Plaisier, Loes, Seelen, Marc A.J., Sanders, Jan-Stephan, Hepkema, Bouke G., Lambeck, Annechien J.A., Bungener, Laura B., Roozendaal, Caroline, Tilanus, Marcel G.J., Voorter, Christina E., Wieten, Lotte, van Duijnhoven, Elly M., Gelens, Marielle A.C.J., Christiaans, Maarten H.L., van Ittersum, Frans J., Nurmohamed, Shaikh A., Lardy, Neubury M., Swelsen, Wendy, van der Pant, Karlijn A.M.I., van der Weerd, Neelke C., ten Berge, Ineke J.M., Bemelman, Frederike J., Hoitsma, Andries, van der Boog, Paul J.M., de Fijter, Johan W., Betjes, Michiel G.H., Otten, Henny G., Roelen, Dave L., and Claas, Frans H.J.
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- 2019
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5. Pre-kidney-transplant blood transfusions do not improve transplantation outcome: a Dutch national study
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Aalten, Jeroen, Bemelman, Frederike J., van den Berg-Loonen, Ella M., Claas, Frans H., Christiaans, Maarten H., de Fijter, Johan W., Hepkema, Bouke G., Hené, Ronald J., van der Heide, Jaap J. Homan, van Hooff, Johannes P., Lardy, Neubury M., Lems, Simon P., Otten, Henderikus G., Weimar, Willem, Allebes, Wil A., and Hoitsma, Andries J.
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- 2009
6. Extensive Variation in Gene Copy Number at the Killer Immunoglobulin-Like Receptor Locus in Humans.
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Vendelbosch, Sanne, de Boer, Martin, Gouw, Remko A. T. W., Ho, Cynthia K. Y., Geissler, Judy, Swelsen, Wendy T. N., Moorhouse, Michael J., Lardy, Neubury M., Roos, Dirk, van den Berg, Timo K., and Kuijpers, Taco W.
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IMMUNOGLOBULINS ,LOCUS (Genetics) ,GENETIC polymorphisms ,CELL-mediated cytotoxicity ,COHORT analysis ,IMMUNITY - Abstract
Killer immunoglobulin-like receptors (KIRs) are involved in the regulation of natural killer cell cytotoxicity. Within the human genome seventeen KIR genes are present, which all contain a large number of allelic variants. The high level of homology among KIR genes has hampered KIR genotyping in larger cohorts, and determination of gene copy number variation (CNV) has been difficult. We have designed a multiplex ligation-dependent probe amplification (MLPA) technique for genotyping and CNV determination in one single assay and validated the results by next-generation sequencing and with a KIR gene-specific short tandem repeat assay. In this way, we demonstrate in a cohort of 120 individuals a high level of CNV for all KIR genes except for the framework genes KIR3DL3 and KIR3DL2. Application of our MLPA assay in segregation analyses of families from the Centre d’Etude du Polymorphisme Humaine, previously KIR-genotyped by classical techniques, confirmed an earlier reported duplication and resulted in the identification of a novel duplication event in one of these families. In summary, our KIR MLPA assay allows rapid and accurate KIR genotyping and CNV detection, thus rendering improved transplantation programs and oncology treatment feasible, and enables more detailed studies on the role of KIRs in human (auto)immunity and infectious disease. [ABSTRACT FROM AUTHOR]
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- 2013
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7. T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation.
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Peereboom ETM, Matern BM, Tomosugi T, Niemann M, Drylewicz J, Joosten I, Allebes WA, van der Meer A, Hilbrands LB, Baas MC, van Reekum FE, Verhaar MC, Kamburova EG, Seelen MAJ, Sanders JS, Hepkema BG, Lambeck AJ, Bungener LB, Roozendaal C, Tilanus MGJ, Voorter CE, Wieten L, van Duijnhoven EM, Gelens MACJ, Christiaans MHL, van Ittersum FJ, Nurmohamed A, Lardy NM, Swelsen W, van der Pant KA, van der Weerd NC, Ten Berge IJM, Bemelman FJ, de Vries APJ, de Fijter JW, Betjes MGH, Roelen DL, Claas FH, Otten HG, Heidt S, van Zuilen AD, Kobayashi T, Geneugelijk K, and Spierings E
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- Adult, Aged, Epitopes, T-Lymphocyte genetics, Female, Graft Rejection genetics, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Graft vs Host Disease mortality, HLA Antigens genetics, Humans, Male, Middle Aged, Retrospective Studies, T-Lymphocytes metabolism, Tissue Donors, Transplant Recipients, Transplantation, Homologous, Treatment Failure, Young Adult, Epitopes, T-Lymphocyte immunology, Graft Rejection immunology, Graft Survival immunology, HLA Antigens immunology, Kidney Transplantation adverse effects, Kidney Transplantation methods, T-Lymphocytes immunology
- Abstract
CD4
+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4+ memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation., Competing Interests: The authors of this manuscript have conflicts of interest to disclose. The UMC Utrecht has filed a patent application on the prediction of an alloimmune response against mismatched HLA. ES is listed as inventor on this patent. MN is employed by PIRCHE AG, which publishes the PIRCHE web-portal. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Peereboom, Matern, Tomosugi, Niemann, Drylewicz, Joosten, Allebes, van der Meer, Hilbrands, Baas, van Reekum, Verhaar, Kamburova, Seelen, Sanders, Hepkema, Lambeck, Bungener, Roozendaal, Tilanus, Voorter, Wieten, van Duijnhoven, Gelens, Christiaans, van Ittersum, Nurmohamed, Lardy, Swelsen, van der Pant, van der Weerd, ten Berge, Bemelman, de Vries, de Fijter, Betjes, Roelen, Claas, Otten, Heidt, van Zuilen, Kobayashi, Geneugelijk and Spierings.)- Published
- 2021
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8. Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients.
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Michielsen LA, van Zuilen AD, Verhaar MC, Wisse BW, Kamburova EG, Joosten I, Allebes WA, van der Meer A, Baas MC, Spierings E, Hack CE, van Reekum FE, Bots ML, Drop ACAD, Plaisier L, Seelen MAJ, Sanders JF, Hepkema BG, Lambeck AJ, Bungener LB, Roozendaal C, Tilanus MGJ, Voorter CE, Wieten L, van Duijnhoven EM, Gelens MACJ, Christiaans MHL, van Ittersum FJ, Nurmohamed SA, Lardy NM, Swelsen W, van der Pant KA, van der Weerd NC, Ten Berge IJM, Bemelman FJ, Hoitsma A, van der Boog PJM, de Fijter JW, Betjes MGH, Heidt S, Roelen DL, Claas FH, Otten HG, and Hilbrands LB
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- Adult, Cohort Studies, Disease-Free Survival, Female, Graft Survival immunology, HLA Antigens immunology, Humans, Immunosuppression Therapy adverse effects, Immunosuppressive Agents therapeutic use, Kidney immunology, Male, Middle Aged, Netherlands epidemiology, Prednisolone, Cyclosporine therapeutic use, Graft Rejection, Immunosuppression Therapy methods, Kidney Transplantation, Mycophenolic Acid therapeutic use, Tacrolimus therapeutic use
- Abstract
Background: Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients., Methods: We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis., Results: Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P < 0.0001) and CsA/Pred (64%, P < 0.0001)., Conclusion: These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
- Published
- 2019
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9. A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival.
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Michielsen LA, Wisse BW, Kamburova EG, Verhaar MC, Joosten I, Allebes WA, van der Meer A, Hilbrands LB, Baas MC, Spierings E, Hack CE, van Reekum FE, Bots ML, Drop ACAD, Plaisier L, Seelen MAJ, Sanders JF, Hepkema BG, Lambeck AJ, Bungener LB, Roozendaal C, Tilanus MGJ, Voorter CE, Wieten L, van Duijnhoven EM, Gelens M, Christiaans MHL, van Ittersum FJ, Nurmohamed SA, Lardy NM, Swelsen W, van der Pant KA, van der Weerd NC, Ten Berge IJM, Bemelman FJ, Hoitsma A, van der Boog PJM, de Fijter JW, Betjes MGH, Heidt S, Roelen DL, Claas FH, Otten HG, and van Zuilen AD
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- Adult, Female, Histocompatibility Antigens Class I, Humans, Kidney Transplantation mortality, Male, Middle Aged, Netherlands, Risk, Tissue Donors, Young Adult, Graft Rejection immunology, Graft Survival immunology, HLA Antigens immunology, Isoantibodies blood
- Abstract
Background: Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs., Methods: To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay., Results: Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P = 0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P = 0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11)., Conclusion: This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
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- 2019
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10. Development and Validation of a Multiplex Non-HLA Antibody Assay for the Screening of Kidney Transplant Recipients.
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Kamburova EG, Kardol-Hoefnagel T, Wisse BW, Joosten I, Allebes WA, van der Meer A, Hilbrands LB, Baas MC, Spierings E, Hack CE, van Reekum FE, van Zuilen AD, Verhaar MC, Bots ML, Drop ACAD, Plaisier L, Meeldijk J, Bovenschen N, Seelen MAJ, Sanders JS, Hepkema BG, Lambeck AJA, Bungener LB, Roozendaal C, Tilanus MGJ, Voorter CE, Wieten L, van Duijnhoven EM, Gelens MACJ, Christiaans MHL, van Ittersum FJ, Nurmohamed SA, Lardy NM, Swelsen W, van der Pant KAMI, van der Weerd NC, Ten Berge IJM, Bemelman FJ, van der Boog PJM, de Fijter JW, Betjes MGH, Heidt S, Roelen DL, Claas FH, and Otten HG
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- Allografts immunology, Graft Rejection blood, Graft Rejection immunology, Graft Survival immunology, Humans, Isoantibodies immunology, Isoantigens immunology, Kidney immunology, Kidney Failure, Chronic surgery, Transplant Recipients, Graft Rejection diagnosis, High-Throughput Screening Assays methods, Histocompatibility Testing methods, Isoantibodies blood, Kidney Transplantation adverse effects
- Abstract
The best treatment for patients with end-stage renal disease is kidney transplantation. Although graft survival rates have improved in the last decades, patients still may lose their grafts partly due to the detrimental effects of donor-specific antibodies (DSA) against human leukocyte antigens (HLA) and to a lesser extent also by antibodies directed against non-HLA antigens expressed on the donor endothelium. Assays to detect anti-HLA antibodies are already in use for many years and have been proven useful for transplant risk stratification. Currently, there is a need for assays to additionally detect multiple non-HLA antibodies simultaneously in order to study their clinical relevance in solid organ transplantation. This study describes the development, technical details and validation of a high-throughput multiplex assay for the detection of antibodies against 14 non-HLA antigens coupled directly to MagPlex microspheres or indirectly via a HaloTag. The non-HLA antigens have been selected based on a literature search in patients with kidney disease or following transplantation. Due to the flexibility of the assay, this approach can be used to include alternative antigens and can also be used for screening of other organ transplant recipients, such as heart and lung.
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- 2018
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11. Extensive Alternative Splicing of KIR Transcripts.
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Bruijnesteijn J, van der Wiel MKH, de Groot N, Otting N, de Vos-Rouweler AJM, Lardy NM, de Groot NG, and Bontrop RE
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- Animals, DNA Copy Number Variations genetics, Exons genetics, Histocompatibility Antigens Class I genetics, Humans, Macaca mulatta, Protein Isoforms genetics, Alternative Splicing genetics, Receptors, KIR genetics
- Abstract
The killer-cell Ig-like receptors (KIR) form a multigene entity involved in modulating immune responses through interactions with MHC class I molecules. The complexity of the KIR cluster is reflected by, for instance, abundant levels of allelic polymorphism, gene copy number variation, and stochastic expression profiles. The current transcriptome study involving human and macaque families demonstrates that KIR family members are also subjected to differential levels of alternative splicing, and this seems to be gene dependent. Alternative splicing may result in the partial or complete skipping of exons, or the partial inclusion of introns, as documented at the transcription level. This post-transcriptional process can generate multiple isoforms from a single KIR gene, which diversifies the characteristics of the encoded proteins. For example, alternative splicing could modify ligand interactions, cellular localization, signaling properties, and the number of extracellular domains of the receptor. In humans, we observed abundant splicing for KIR2DL4 , and to a lesser extent in the lineage III KIR genes. All experimentally documented splice events are substantiated by in silico splicing strength predictions. To a similar extent, alternative splicing is observed in rhesus macaques, a species that shares a close evolutionary relationship with humans. Splicing profiles of Mamu-KIR1D and Mamu-KIR2DL04 displayed a great diversity, whereas Mamu-KIR3DL20 (lineage V) is consistently spliced to generate a homolog of human KIR2DL5 (lineage I). The latter case represents an example of convergent evolution. Although just a single KIR splice event is shared between humans and macaques, the splicing mechanisms are similar, and the predicted consequences are comparable. In conclusion, alternative splicing adds an additional layer of complexity to the KIR gene system in primates, and results in a wide structural and functional variety of KIR receptors and its isoforms, which may play a role in health and disease.
- Published
- 2018
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12. Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure.
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Kamburova EG, Wisse BW, Joosten I, Allebes WA, van der Meer A, Hilbrands LB, Baas MC, Spierings E, Hack CE, van Reekum FE, van Zuilen AD, Verhaar MC, Bots ML, Drop ACAD, Plaisier L, Seelen MAJ, Sanders JS, Hepkema BG, Lambeck AJA, Bungener LB, Roozendaal C, Tilanus MGJ, Voorter CE, Wieten L, van Duijnhoven EM, Gelens MACJ, Christiaans MHL, van Ittersum FJ, Nurmohamed SA, Lardy NM, Swelsen W, van der Pant KAMI, van der Weerd NC, Ten Berge IJM, Bemelman FJ, Hoitsma AJ, van der Boog PJM, de Fijter JW, Betjes MGH, Heidt S, Roelen DL, Claas FH, and Otten HG
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- Adult, Age Distribution, Antilymphocyte Serum immunology, Cohort Studies, Female, Follow-Up Studies, Graft Rejection epidemiology, Humans, Incidence, Kidney Transplantation methods, Male, Middle Aged, Preoperative Care methods, Retrospective Studies, Risk Assessment, Sex Distribution, Tissue Donors, Transplant Recipients statistics & numerical data, Transplantation Immunology, Antibodies, Anti-Idiotypic immunology, Complement C3d immunology, Graft Rejection immunology, HLA Antigens immunology, Kidney Transplantation adverse effects, Registries
- Abstract
Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P =0.93). Patients without DSA had a 10-year graft survival of 78%. Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure., (Copyright © 2018 by the American Society of Nephrology.)
- Published
- 2018
- Full Text
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