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San Segundo D, Comins-Boo A, López-Hoyos M. Anti-Human Leukocyte Antigen Antibody Detection from Terasaki's Humoral Theory to Delisting Strategies in 2024. Int J Mol Sci 2025; 26:630. [PMID: 39859344 PMCID: PMC11766285 DOI: 10.3390/ijms26020630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/03/2025] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
The human leukocyte antigen (HLA) system plays a critical role in transplant immunology, influencing outcomes through various immune-mediated rejection mechanisms. Hyperacute rejection is driven by preformed donor-specific antibodies (DSAs) targeting HLAs, leading to complement activation and graft loss within hours to days. Acute rejection typically occurs within six months post-transplantation, involving cellular and humoral responses, including the formation of de novo DSAs. Chronic rejection, a key factor in long-term graft failure, often involves class II DSAs and complex interactions between the innate and adaptive immune systems. Advancements in HLA antibody detection, particularly single antigen bead (SAB) assays, have improved the sensitivity and characterization of DSAs. However, these assays face challenges like false positives from denatured antigens and false negatives due to low antibody titers or complement competition. Furthermore, molecular mismatch (MM) analysis has emerged as a potential tool for refining donor-recipient compatibility but faces some issues such as a lack of standardization. Highly sensitized patients with calculated panel-reactive antibodies (cPRA) of 100% face barriers to transplantation. Strategies like serum dilution, novel therapies (e.g., Imlifidase), and delisting approaches could refine immunological risk assessment and delisting strategies are essential to expand transplant opportunities for these patients.
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Affiliation(s)
- David San Segundo
- Immunology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (D.S.S.); (A.C.-B.)
- Institute for Research Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
| | - Alejandra Comins-Boo
- Immunology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (D.S.S.); (A.C.-B.)
- Institute for Research Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
| | - Marcos López-Hoyos
- Immunology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (D.S.S.); (A.C.-B.)
- Institute for Research Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
- Departamento de Biología Molecular, Universidad de Cantabria, 39011 Santander, Spain
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2
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Philogene MC, Timofeeva OA, Gimferrer I, Hod-Dvorai R. Assessment of Inter-Laboratory Variability for Flow Cytometric Crossmatch Testing: Lessons Learned from Proficiency Surveys. Hum Immunol 2025; 86:111176. [PMID: 39626409 DOI: 10.1016/j.humimm.2024.111176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/27/2024] [Accepted: 11/04/2024] [Indexed: 01/25/2025]
Abstract
Detection of antibody directed against human leukocyte antigens (HLA) using a combination of flow cytometric crossmatch (FCXM) and antibody tests, is an important responsibility of Histocompatibility laboratories. Proficiency testing surveys utilize the results of these assays to assess concordance across multiple laboratories. In this study, we reviewed the ASHI Proficiency Testing (PT) antibody and crossmatching (AC) survey results obtained over a 6-year period, to evaluate the degree and nature of inter-laboratory FCXM and antibody assay variability. National and international laboratories representing 22 countries produced >10,000 T cell and >10,000 B cell FCXM results. Based on the 80% consensus threshold established for FCXM surveys, 92.5% T cell FCXM and 91.7% B cell FCXM results reached positive or negative consensus and were respectively consistent with the presence or absence of donor specific HLA antibodies (DSA) that reached a 90% consensus. The 7.5% of T cell and 8.3% of B cell FCXM results that did not reach consensus were associated with a combination of consensus and non-consensus DSA. This analysis shows that despite differences in testing protocols and algorithms, there is good consensus for the FCXM assay among laboratories. The data show correlation between FCXM and bead-based assays and support the use of both for reliable information when assessing immunological risk.
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Affiliation(s)
- Mary Carmelle Philogene
- Histocompatibility and Immunogenetics Laboratory, Virginia Commonwealth University, Richmond, VA, United States.
| | - Olga A Timofeeva
- UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States
| | - Idoia Gimferrer
- Immunogenetics/HLA Laboratory at Bloodworks NorthWest, Seattle, WA, United States
| | - Reut Hod-Dvorai
- Department of Pathology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, United States
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3
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Kongtim P, Vittayawacharin P, Zou J, Srour S, Shaffer B, Shapiro RM, Varma A, McGuirk J, Dholaria BR, McCurdy SR, DeZern AE, Bejanyan N, Bashey A, Furst S, Castagna L, Mariotti J, Ruggeri A, Bailen R, Teshima T, Xiao-Jun H, Bonfim C, Aung F, Cao K, Carpenter PA, Hamadani M, Askar M, Fernandez-Vina M, Girnita A, Ciurea SO. ASTCT Consensus Recommendations on Testing and Treatment of Patients with Donor-specific Anti-HLA Antibodies. Transplant Cell Ther 2024; 30:1139-1154. [PMID: 39260570 DOI: 10.1016/j.jtct.2024.09.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 09/04/2024] [Indexed: 09/13/2024]
Abstract
Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers. Additional testing to determine risk of allograft rejection may include assays with HLA antigens in natural conformation, such as flow cytometric crossmatch, and/or antibody binding assays, such as C1q testing. Patients with low level of DSA (<2,000 mean fluorescence intensity; MFI) may not require treatment, while others with very high level of DSA (>20,000 MFI) may be at very high-risk for engraftment failure despite current therapies. By contrast, in patients with moderate or high level of DSA, desensitization therapy can successfully mitigate DSA levels and improve donor cell engraftment rate, with comparable outcomes to patients without DSA. Treatment is largely empirical and multimodal, involving the removal, neutralization, and blocking of antibodies, as well as inhibition of antibody production to prevent activation of the complement cascade. Desensitization protocols are based on accumulated multicenter experience, while prospective multicenter studies remain lacking. Most patients require a full intensity protocol that includes plasma exchange, while protocols relying only on rituximab and intravenous immunoglobulin may be sufficient for patients with lower DSA levels and negative C1q and/or flow cytometric crossmatch. Monitoring DSA levels before and after HSCT could guide preemptive treatment when high levels persist after stem cell infusion. This paper aims to standardize current evidence-based practice and formulate future directions to improve upon current knowledge and advance treatment for this relatively rare, but potentially serious complication in allogeneic HSCT recipients.
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Affiliation(s)
- Piyanuch Kongtim
- Hematopoietic Stem Cell Transplant and Cellular Therapy Program, Division of Hematology and Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA
| | - Pongthep Vittayawacharin
- Hematopoietic Stem Cell Transplant and Cellular Therapy Program, Division of Hematology and Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA
| | - Jun Zou
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Samer Srour
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Brian Shaffer
- Adult BMT Service, Department of Internal Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Roman M Shapiro
- Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Ankur Varma
- Section of Bone Marrow Transplant and Cell Therapy, Division of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AK, USA
| | - Joseph McGuirk
- Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Medical Center, Kansas City, KS, USA
| | | | - Shannon R McCurdy
- Division of Hematology and Oncology and Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadephia, PA, USA
| | - Amy E DeZern
- Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Nelli Bejanyan
- Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA
| | - Asad Bashey
- BMT, Acute Leukemia and Cellular Immunotherapy Program at Northside Hospital, Blood and Marrow Transplant Group of Georgia, Atlanta, GA, USA
| | - Sabine Furst
- Programme de Transplantation et d'Immunothérapie Cellulaire, Département d'Hématologie, Institut Paoli Calmettes, Marseille, France
| | - Luca Castagna
- BMT Unit, Ospedale Villa Sofia Cervello, Palermo, Italy
| | - Jacopo Mariotti
- Department of Oncology/Hematology, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Annalisa Ruggeri
- Hematology and BMT unit, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Rebeca Bailen
- Hematology and Hemotherapy Department, Gregorio Marañon University Hospital, Gregorio Marañon Health Research Institute, Madrid, Spain
| | - Takanori Teshima
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Huang Xiao-Jun
- Peking University Institute of Hematology, Beijing, China
| | - Carmen Bonfim
- Pele Pequeno Principe Research institute/Faculdades Pequeno Principe, Curitiba, Brazil
| | - Fleur Aung
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Kai Cao
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Paul A Carpenter
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | | | - Medhat Askar
- College of Medicine, Qatar University, Doha; Qatar and National Marrow Donor Program, Minneapolis, MN
| | | | - Alin Girnita
- HLA Laboratory, Department of Pathology, University of California Irvine, Irvine, CA, USA
| | - Stefan O Ciurea
- Hematopoietic Stem Cell Transplant and Cellular Therapy Program, Division of Hematology and Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA.
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Ziemann M, Lindemann M, Hallensleben M, Altermann W, Althaus K, Budde K, Einecke G, Eisenberger U, Ender A, Feldkamp T, Grahammer F, Guthoff M, Holzmann-Littig C, Hugo C, Kauke T, Kemmner S, Koch M, Lachmann N, Marget M, Morath C, Nitschke M, Renders L, Scherer S, Stumpf J, Schwenger V, Sommer F, Spriewald B, Süsal C, Zecher D, Heinemann FM, Verboom M. Risk Stratification Before Living Donor Kidney Transplantation in Patients With Preformed Donor-specific Antibodies by Different Crossmatch Methods. Transplant Direct 2024; 10:e1680. [PMID: 39131238 PMCID: PMC11315586 DOI: 10.1097/txd.0000000000001680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 05/22/2024] [Indexed: 08/13/2024] Open
Abstract
Background Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients are scarce. Methods DSA-positive living kidney transplant recipients were selected from a multicenter study examining 4233 consecutive renal transplants. An additional 7 patients from 2 further centers were included. Flow cytometric crossmatches (FXM), Luminex-based crossmatches, and virtual crossmatches based on C1q- and C3d-binding antibodies (C1qXM and C3dXM) were performed retrospectively using pretransplant sera and lymphocytes isolated from fresh samples. These samples were obtained from 44 donor and recipient pairs from 12 centers. Clinical outcome data and the control group without DSA were compiled from the previous study and were supplemented by data on 10-y death-censored graft survival (10yGS). Results Between 19% (C3dXM) and 46% (FXM) of crossmatches were positive. Crossmatch-positive patients showed high incidences of antibody-mediated rejection (AMR) within 6 mo (up to 60% in B-cell FXM+ patients). The incidence of AMR in crossmatch-negative patients ranged between 5% (FXM-) and 13% (C1qXM-). 10yGS was significantly impaired in patients with positive T-cell FXM and total FXM compared with both patients without DSA and those with DSA with negative FXM. Conclusions Especially FXM are useful for risk stratification, as the outcome of DSA-positive, FXM-negative patients is similar to that of DSA-negative patients, whereas FXM-positive patients have both more AMR and decreased 10yGS. Because of their lower sensitivity, the significance of Luminex-based crossmatches, C1qXM, and C3dXM would have to be examined in patients with stronger DSA.
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Affiliation(s)
- Malte Ziemann
- Institute for Transfusion Medicine, University Hospital of Schleswig-Holstein, Lübeck, Germany
| | - Monika Lindemann
- Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany
| | - Michael Hallensleben
- Institute for Transfusion Medicine, Medizinische Hochschule Hannover, Hannover, Germany
| | - Wolfgang Altermann
- Institute for Transfusion Medicine, University Hospital Halle, Halle, Germany
| | - Karina Althaus
- Institute for Clinical and Experimental Transfusion Medicine, University Hospital of Tübingen, Tübingen, Germany
- Center for Clinical Transfusion Medicine, Tübingen, Germany
| | - Klemens Budde
- Medizinische Klinik m. S. Nephrologie, Charité–Universitätsmedizin Berlin, Berlin, Germany
| | - Gunilla Einecke
- Klinik für Nieren- und Hochdruckerkrankungen, Medizinische Hochschule Hannover, Hannover, Germany
| | - Ute Eisenberger
- Klinik für Nephrologie, University Hospital Essen, Essen, Germany
| | - Andrea Ender
- Institute for Transfusion Medicine, Klinikum der Landeshauptstadt Stuttgart, Stuttgart, Germany
| | - Thorsten Feldkamp
- Transplant Center, University Hospital of Schleswig-Holstein, Kiel, Germany
| | - Florian Grahammer
- III. Medizinische Klinik und Poliklinik für Nephrologie, Rheumatologie und Endokrinologie, University Hospital Hamburg Eppendorf, Hamburg, Germany
- Hamburg Center for Kidney Health, University Hospital Hamburg Eppendorf, Hamburg, Germany
| | - Martina Guthoff
- Medizinische Klinik IV, Sektion Nieren- und Hochdruckkrankheiten, University Hospital Tübingen, Tübingen, Germany
| | | | - Christian Hugo
- Medizinische Klinik III, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Teresa Kauke
- Abteilung für Transfusionsmedizin, Zelltherapeutika und Hämostaseologie, Labor für Immungenetik, Klinik für Anästhesiologie, Klinikum der Universität München, München, Germany
- Abteilung Thoraxchirurgie, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Klinikum der Universität München, München, Germany
- Transplant Center, Klinikum der Universität München, München, Germany
| | - Stephan Kemmner
- Transplant Center, Klinikum der Universität München, München, Germany
| | - Martina Koch
- Hepatobiliäre Chirurgie und Transplantationschirurgie, University Hospital Hamburg, Hamburg, Germany
| | - Nils Lachmann
- HLA-Labor, Charité–Universitätsmedizin Berlin, Berlin, Germany
| | - Matthias Marget
- Institute for Transfusion Medicine, University Hospital Hamburg, Hamburg, Germany
| | - Christian Morath
- Zentrum für Innere Medizin, Nephrologie, University Hospital Heidelberg, Heidelberg, Germany
| | - Martin Nitschke
- Transplant Center, University Hospital of Schleswig-Holstein, Lübeck, Germany
| | - Lutz Renders
- Nephrologie, Klinikum Rechts der Isar, Technische Universität München, München, Germany
| | - Sabine Scherer
- Institut für Immunologie, Transplantationsimmunologie, University Hospital Heidelberg, Heidelberg, Germany
| | - Julian Stumpf
- Medizinische Klinik III, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Vedat Schwenger
- Klinik für Nieren-, Hochdruck- und Autoimmunerkrankungen, Klinikum der Landeshauptstadt Stuttgart, Stuttgart, Germany
| | - Florian Sommer
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, University Hospital Augsburg, Augsburg, Germany
| | - Bernd Spriewald
- Medizinische Klinik 5–Hämatologie und Internistische Onkologie, University Hospital Erlangen, Erlangen, Germany
| | - Caner Süsal
- Institut für Immunologie, Transplantationsimmunologie, University Hospital Heidelberg, Heidelberg, Germany
| | - Daniel Zecher
- Department of Nephrology, University Hospital Regensburg, Regensburg, Germany
| | - Falko M. Heinemann
- Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany
| | - Murielle Verboom
- Institute for Transfusion Medicine, Medizinische Hochschule Hannover, Hannover, Germany
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5
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Tafulo S, Osório E, Mendes C, Liwski R. Complement-dependent cytotoxicity crossmatch in solid organ transplantation: The gold standard or golden history? Hum Immunol 2024; 85:110734. [PMID: 38030522 DOI: 10.1016/j.humimm.2023.110734] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/19/2023] [Accepted: 11/20/2023] [Indexed: 12/01/2023]
Abstract
Complement-dependent cytotoxicity crossmatch (CDC-XM) has been considered for many years the standard of practice for determining compatibility in solid organ transplantation (SOT). However, as this method is laborious, time intensive and lacks sensitivity and specificity, it has been replaced in many laboratories worldwide by flow cytometry crossmatch (FCXM) and/or virtual crossmatch (vXM). With this study we intend to show the relevance of performing CDC-XM in the era of virtual crossmatching. We retrospectively analyzed 1,007 consecutive T and B cell deceased donor (DD) CDC-XMs performed in parallel using non-treated and dithiothreitol (DTT) treated sera between May 2022 and January 2023 in waitlisted patients with no donor specific antibodies (DSA) against HLA-A, B and/or DR antigens. Thirty five of 1,007 (3.5%) T cell crossmatches and 132 of 1,007 (13.1%) B cell crossmatches were positive with non-treated sera. Correlation with the vXM demonstrated no DSA in any of the positive T cell crossmatches. DSA were also absent in 126/132 positive B cell crossmatches, indicating a high rate of false positive CDC-XM. Indeed, only 4/35 T cell and 13/132 B cell CDC-XM remained positive after treatment with DTT, confirming that false positive reactivity with non-treated sera is high. Class I HLA DSA against C locus antigens were present in 17/1,007 T cell crossmatches and none were detected by CDC-XM (sensitivity = 0%). Similarly, only 6/77 B cell crossmatches with DSA targeting HLA-C, DQ and/or DP antigens were CDC-XM positive (sensitivity = 7.8%). Furthermore, only 4/6 positive B cell CDC-XM were confirmed to have complement binding potential using the C1q assay, suggesting additional false positive reactivity in 2/6 of the positive CDC-XM. Our study demonstrates that CDC-XM exhibits poor sensitivity, high false positive reactivity (especially without DTT treatment) and does not meaningfully contribute to pre-transplant compatibility testing in the context of vXM based allocation. Furthermore, the use of CDC-XM can unnecessarily delay or even prevent safe and appropriate transplant allocation.
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Affiliation(s)
- Sandra Tafulo
- Centro de Sangue e da Transplantação do Porto, Instituto Português do Sangue e da Transplantação, Porto, Portugal; UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal
| | - Ermelinda Osório
- Centro de Sangue e da Transplantação do Porto, Instituto Português do Sangue e da Transplantação, Porto, Portugal
| | - Cecília Mendes
- Centro de Sangue e da Transplantação do Porto, Instituto Português do Sangue e da Transplantação, Porto, Portugal
| | - Robert Liwski
- Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
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Rocha Y, Jaramillo A, Neumann J, Hacke K, Palou E, Torres J. Crossmatch assays in transplantation: Physical or virtual?: A review. Medicine (Baltimore) 2023; 102:e36527. [PMID: 38115324 PMCID: PMC10727546 DOI: 10.1097/md.0000000000036527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/16/2023] [Accepted: 11/17/2023] [Indexed: 12/21/2023] Open
Abstract
The value of the crossmatch test in assessing pretransplant immunological risk is vital for clinical decisions, ranging from the indication of the transplant to the guidance of induction protocols and treatment with immunosuppressants. The crossmatch tests in transplantation can be physical or virtual, each with its advantages and limitations. Currently, the virtual crossmatch stands out for its sensitivity and specificity compared to the physical tests. Additionally, the virtual crossmatch can be performed in less time, allowing for a reduction in cold ischemia time. It shows a good correlation with the results of physical tests and does not negatively impact graft survival. Proper communication between clinicians and the transplant immunology laboratory will lead to a deeper understanding of each patient's immunological profile, better donor-recipient selection, and improved graft survival.
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Affiliation(s)
| | - Andrés Jaramillo
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ
| | - Jorge Neumann
- Transplant Immunology Laboratory, Santa Casa Hospital, Porto Alegre, Brazil
| | - Katrin Hacke
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ
| | - Eduard Palou
- Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Juan Torres
- Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona, Spain
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7
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Chauhan R, Tiwari AK, Aggarwal G, Gowri Suresh L, Kumar M, Bansal SB. Low-MFI (median fluorescence intensity) pre-transplant DSA (donor specific antibodies) leading to anamnestic antibody mediated rejection in live-related donor kidney transplantation. Transpl Immunol 2023; 81:101931. [PMID: 37730185 DOI: 10.1016/j.trim.2023.101931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/11/2023] [Accepted: 09/16/2023] [Indexed: 09/22/2023]
Abstract
"In solid organ transplantation, the compatibility between recipient and donor relies on testing prior to transplantation as a major determinant for the successful transplant outcomes. This compatibility testing depends on the detection of donor-specific antibodies (DSAs) present in the recipient. Indeed, sensitized transplant candidates are at higher risk of allograft rejection and graft loss compared to non-sensitized individuals. Most of the laboratories in India have adopted test algorithms for the appropriate risk stratification of transplants, namely: 1) donor cell-based flow-cytometric cross-match (FCXM) assay with patient's serum to detect DSAs; 2) HLA-coated beads to detect anti-HLA antibodies; and 3) complement-dependent cytotoxicity crossmatch (CDCXM) with donor cells to detect cytotoxic antibodies. In the risk stratification strategy, laboratories generally accept a DSA median fluorescence index (MFI) of 1000 MFI or lower MFI (low-MFI) as a negative value and clear the patient for the transplant. We present two cases of live-related donor kidney transplants (LDKTs) with low-MFI pre-transplant DSA values who experienced an early acute antibody-mediated rejection (ABMR) as a result of an anamnestic antibody response by DSA against HLA class II antibodies. These results were confirmed by retesting of both pre-transplant and post-transplant archived sera from patients and freshly obtained donor cells. Our examples indicate a possible ABMR in patients with low MFI pre-transplant DSA. Reclassification of low vs. high-risk may be appropriate for sensitized patients with low-MFI DSA."
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Affiliation(s)
- Rajni Chauhan
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-Gurugram, India
| | - Aseem Kumar Tiwari
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-Gurugram, India.
| | - Geet Aggarwal
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-Gurugram, India
| | - L Gowri Suresh
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-Gurugram, India
| | - Mohit Kumar
- Molecular and Transplant Immunology Laboratory, Department of Transfusion Medicine, Medanta-Gurugram, India
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8
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Kahler D, Curtis H, Zhao H, Diamond A, Di Carlo A, Karhadkar S. Deciphering the True Immunologic Risk in Renal Transplantation in Patients With HIV. Transplant Proc 2023; 55:2392-2397. [PMID: 37932184 DOI: 10.1016/j.transproceed.2023.09.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 09/26/2023] [Accepted: 09/26/2023] [Indexed: 11/08/2023]
Abstract
Since 1995, rates of end-stage renal disease have risen dramatically in patients living with HIV infection. However, given the concern for higher rates of acute rejection in this patient population, the immunologic threat posed by HIV infection is a specter clinicians must continually confront. Living donor transplantation may negate this risk; this study aims to assess the benefit of living donor transplantation in this population and to ascertain the immunologic risk faced by patients who are HIV-infected. The 2021 UNOS database was queried, and all HIV-infected kidney transplant recipients since 1987 were identified. Recipients were stratified based on deceased (DDKT) vs living (LDKT) donor status. Overall survival, allograft survival, acute rejection, panel reactive antibody (PRA) percentage, and crossmatch positivity were compared between groups. One thousand two hundred twenty-six patients underwent DDKT, and 304 patients underwent LDKT. Living donor kidney transplantation demonstrated greater overall survival (P = .045) and graft survival (P < .001). However, no difference in acute rejection was noted between the cohorts, and no difference in overall or graft survival was evident based on PRA percentage. Crossmatch positive status did not negatively affect graft survival. Patients with HIV undergoing LDKT fared better than those undergoing DDKT. Nevertheless, patients at higher immunologic risk-elevated PRA% and crossmatch positivity-did not experience graft loss at a higher rate than patients at lower immunologic risk. These results were valid in both DDKT and LDKT cohorts. These findings suggest that infection with HIV does not overtly increase patients' immunologic risk, and concerns surrounding transplantation in this population may be overestimated.
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Affiliation(s)
- Dylan Kahler
- Department of Surgery, Temple University Hospital, Philadelphia, PA
| | - Houston Curtis
- Lewis Katz School of Medicine at Temple University, Philadelphia, PA
| | - Huaqing Zhao
- Center for Biostatistics and Epidemiology, Department of Biomedical Education and Data Science, Lewis Katz School of Medicine at Temple University, Philadelphia, PA
| | - Adam Diamond
- Department of Pharmacy, Temple University Hospital, Philadelphia, PA
| | - Antonio Di Carlo
- Division of Abdominal Organ Transplant Surgery, Department of Surgery, Temple University Hospital, Philadelphia, PA
| | - Sunil Karhadkar
- Division of Abdominal Organ Transplant Surgery, Department of Surgery, Temple University Hospital, Philadelphia, PA.
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9
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Tamargo CL, Kant S. Pathophysiology of Rejection in Kidney Transplantation. J Clin Med 2023; 12:4130. [PMID: 37373823 PMCID: PMC10299312 DOI: 10.3390/jcm12124130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/07/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Kidney transplantation has been the optimal treatment for end-stage kidney disease for almost 70 years, with increasing frequency over this period. Despite the prevalence of the procedure, allograft rejection continues to impact transplant recipients, with consequences ranging from hospitalization to allograft failure. Rates of rejection have declined over time, which has been largely attributed to developments in immunosuppressive therapy, understanding of the immune system, and monitoring. Developments in these therapies, as well as an improved understanding of rejection risk and the epidemiology of rejection, are dependent on a foundational understanding of the pathophysiology of rejection. This review explains the interconnected mechanisms behind antibody-mediated and T-cell-mediated rejection and highlights how these processes contribute to outcomes and can inform future progress.
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Affiliation(s)
- Christina L. Tamargo
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA;
| | - Sam Kant
- Division of Nephrology & Comprehensive Transplant Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
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10
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Schneider MM, Scheidt T, Priddey AJ, Xu CK, Hu M, Meisl G, Devenish SRA, Dobson CM, Kosmoliaptsis V, Knowles TPJ. Microfluidic antibody affinity profiling of alloantibody-HLA interactions in human serum. Biosens Bioelectron 2023; 228:115196. [PMID: 36921387 DOI: 10.1016/j.bios.2023.115196] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 02/17/2023] [Accepted: 03/03/2023] [Indexed: 03/07/2023]
Abstract
Antibody profiling is a fundamental component of understanding the humoral response in a wide range of disease areas. Most currently used approaches operate by capturing antibodies onto functionalised surfaces. Such measurements of surface binding are governed by an overall antibody titre, while the two fundamental molecular parameters, antibody affinity and antibody concentration, are challenging to determine individually from such approaches. Here, by applying microfluidic diffusional sizing (MDS), we show how we can overcome this challenge and demonstrate reliable quantification of alloantibody binding affinity and concentration of alloantibodies binding to Human Leukocyte Antigens (HLA), an extensively used clinical biomarker in organ transplantation, both in buffer and in crude human serum. Capitalising on the ability to vary both serum and HLA concentrations during MDS, we show that both affinity and concentration of HLA-specific antibodies can be determined directly in serum when neither of these parameters is known. Finally, we provide proof of principle in clinical transplant patient sera that our assay enables differentiation of alloantibody reactivity against HLA proteins of highly similar structure, providing information not attainable through currently available techniques. These results outline a path towards detection and in-depth profiling of humoral immunity and may enable further insights into the clinical relevance of antibody reactivity in clinical transplantation and beyond.
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Affiliation(s)
- Matthias M Schneider
- Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
| | - Tom Scheidt
- Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
| | - Ashley J Priddey
- Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK
| | - Catherine K Xu
- Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
| | - Mengsha Hu
- Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
| | - Georg Meisl
- Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
| | - Sean R A Devenish
- Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Rd, Cambridge, CB1 8DH, UK
| | - Christopher M Dobson
- Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
| | - Vasilis Kosmoliaptsis
- Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Hills Road, Cambridge, CB2 0QQ, UK; NIHR Cambridge Biomedical Research Centre, Hills Road, Cambridge, CB2 0QQ, UK.
| | - Tuomas P J Knowles
- Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK; Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Ave, Cambridge, CB3 0HE, UK.
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11
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Silva BDPC, Lasmar MF, Nascimento E, Fabreti-Oliveira RA. Impact of early blood transfusion after kidney transplantation on the clinical outcomes and allograft survival. Transpl Immunol 2023; 77:101807. [PMID: 36842568 DOI: 10.1016/j.trim.2023.101807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 02/21/2023] [Accepted: 02/21/2023] [Indexed: 02/26/2023]
Abstract
INTRODUCTION Anemia in chronic kidney disease is of great concern regarding blood transfusions and the possibility of allosensitization for future kidney transplants and the occurrence of rejection and allograft loss in the post-transplant period. The aim of this study was to evaluate the effect of early blood transfusion on the occurrence of rejections, allograft function and survival in the first year after transplantation. MATERIAL AND METHODS This retrospective study was carried out with 445 patients submitted to kidney transplant allocated to two groups. The first group received early blood transfusions after transplant (n = 125, 28.09%), and the second group did not receive blood transfusions (n = 320, 71.91%). The patient outcomes were evaluated during a 1-year follow-up. RESULTS 14 patients given blood transfusion (11.2%) lost their allograft in the first year in comparison with 8 (2.5%) without transfusion (p < 0.001). There were 9 deaths in each group, which corresponded to 7.2% of the patients who received blood transfusions and 2.81% of those who did not (p < 0.035). Patient hospitalization lasted 15 days in transfusion group and 8.5 days in non-transfusion group (p < 0.001). Creatinine levels were higher in the patients who received blood transfusion than in those without transfusion in the first and third months after transplantation (p = 0.012 and 0.038, respectively). During the first year, the patients who received blood products experienced more antibody-mediated rejection (ABMR) (13.60%) than patients who did not (4.38%) (p < 0.001). Those who received blood transfusions also developed de novo DSA in higher proportion than those without transfusion against both class I and class II HLA (p < 0.001). CONCLUSION This study showed that blood transfusions in the first month after transplantation had a negative impact on kidney function, graft survival, and contributed to the development of de novo DSA, an increased risk of ABMR and infections.
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Affiliation(s)
- Bernardo D P C Silva
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil; University Hospital of the Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil.
| | - Marcus Faria Lasmar
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil; University Hospital of the Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil
| | - Evaldo Nascimento
- IMUNOLAB - Laboratory of Histocompatibility, Belo Horizonte, Minas Gerais, Brazil; Institute of Research and Education of the Hospital Santa Casa, Belo Horizonte, Minas Gerais, Brazil..
| | - Raquel A Fabreti-Oliveira
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil; IMUNOLAB - Laboratory of Histocompatibility, Belo Horizonte, Minas Gerais, Brazil.
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12
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Muñoz-Herrera CM, Gutiérrez-Bautista JF, López-Nevot MÁ. Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation. J Clin Med 2023; 12:2335. [PMID: 36983335 PMCID: PMC10057312 DOI: 10.3390/jcm12062335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 02/24/2023] [Accepted: 02/24/2023] [Indexed: 03/19/2023] Open
Abstract
BACKGROUND Antibody-mediated rejection (AMR) is one of the most important challenges in the context of renal transplantation, because the binding of de novo donor-specific antibodies (dnDSA) to the kidney graft triggers the activation of the complement, which in turn leads to loss of transplant. In this context, the objective of this study was to evaluate the association between complement-fixing dnDSA antibodies and graft loss as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients. METHODS Our study included a cohort of 245 transplant patients over a 5-year period at Virgen de las Nieves University Hospital (HUVN) in Granada, Spain. RESULTS dnDSA was observed in 26 patients. Of these patients, 17 had non-complement-fixing dnDSA and 9 had complement-fixing dnDSA. CONCLUSIONS Our study demonstrated a significant association between the frequency of rejection and renal graft loss and the presence of C1q-binding dnDSA. Our results show the importance of the individualization of dnDSA, classifying them according to their ability to activate the complement, and suggest that the detection of complement-binding capacity by dnDSA could be used as a prognostic marker to predict AMR outcome and graft survival in kidney transplant patients who develop dnDSA.
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Affiliation(s)
- Claudia M. Muñoz-Herrera
- Departamento de Bioquímica, Biología Molecular e Inmunología III, University of Granada, 18010 Granada, Spain
- Programa de Doctorado en Biomedicina, University of Granada, 18010 Granada, Spain
- Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain
- Clínica Imbanaco Grupo Quirónsalud, Laboratorio Clínico, Patología y Servicio de Transfusión, Laboratorio de Inmunogenética, 760042 Cali, Colombia
| | - Juan Francisco Gutiérrez-Bautista
- Departamento de Bioquímica, Biología Molecular e Inmunología III, University of Granada, 18010 Granada, Spain
- Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain
| | - Miguel Ángel López-Nevot
- Departamento de Bioquímica, Biología Molecular e Inmunología III, University of Granada, 18010 Granada, Spain
- Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain
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13
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Di Cocco P, Gaitonde S, Spaggiari M, Fratti A, Alvarez JA, Petrochenkov E, Valdenepas BT, Gupta P, Benedetti E, Tzvetanov I. Desensitizing With Temporary Donor Splenic Transplant: Hope for the Sensitized Patients on Pancreas and Kidney -Pancreas Transplant Waitlist. Transplant Proc 2023; 55:295-302. [PMID: 36801174 DOI: 10.1016/j.transproceed.2023.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 12/20/2022] [Accepted: 01/24/2023] [Indexed: 02/21/2023]
Abstract
BACKGROUND Sensitized patients on a waitlist with donor specific antibodies (DSA) or positive flow cytometry cross match (FXM) to deceased donor organ have few pretransplant desensitization options due to increasing graft cold ischemia time. Herein, sensitized simultaneous kidney/pancreas recipients received temporary splenic transplant from the same donor under the hypothesis that spleen would function as a DSA graveyard and provide a safe immunologic window for transplant. METHODS We analyzed presplenic and postsplenic transplant FXM and DSA results of 8 sensitized patients who underwent simultaneous kidney and pancreas transplantation with temporary deceased donor spleen between November 2020 and January 2022. RESULTS Pre-splenic transplant, 4 sensitized patients were both T-cell and B-cell FXM positive; one was only B-cell FXM positive and 3 were DSA positive/FXM negative. Post-splenic transplant, all were FXM negative. Pre-splenic transplant class I and class II DSA were detected in 3 patients, only class I DSA in 4 patients, and only class II DSA in 1 patient. Postsplenic transplant, class I DSA was eliminated in all patients. Class II DSA persisted in 3 patients; all showed a marked decrease in DSA mean fluorescence index. Class II DSA was eliminated in one patient. CONCLUSION Donor spleen functions as a DSA graveyard and provides an immunologically safe window for kidney-pancreas transplantation.
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Affiliation(s)
| | - Sujata Gaitonde
- Department of Pathology, University of Illinois at Chicago, Illinois.
| | - Mario Spaggiari
- Department of Surgery, University of Illinois at Chicago, Illinois
| | - Alberto Fratti
- Department of Surgery, University of Illinois at Chicago, Illinois
| | | | | | - Bentio T Valdenepas
- Department of Pharmacy Practice, University of Illinois at Chicago, Illinois
| | - Priyanka Gupta
- Department of Pathology, University of Illinois at Chicago, Illinois
| | - Enrico Benedetti
- Department of Surgery, University of Illinois at Chicago, Illinois
| | - Ivo Tzvetanov
- Department of Surgery, University of Illinois at Chicago, Illinois
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14
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Frutos MÁ, Crespo M, Valentín MDLO, Alonso-Melgar Á, Alonso J, Fernández C, García-Erauzkin G, González E, González-Rinne AM, Guirado L, Gutiérrez-Dalmau A, Huguet J, Moral JLLD, Musquera M, Paredes D, Redondo D, Revuelta I, Hofstadt CJVD, Alcaraz A, Alonso-Hernández Á, Alonso M, Bernabeu P, Bernal G, Breda A, Cabello M, Caro-Oleas JL, Cid J, Diekmann F, Espinosa L, Facundo C, García M, Gil-Vernet S, Lozano M, Mahillo B, Martínez MJ, Miranda B, Oppenheimer F, Palou E, Pérez-Saez MJ, Peri L, Rodríguez O, Santiago C, Tabernero G, Hernández D, Domínguez-Gil B, Pascual J. Recommendations for living donor kidney transplantation. Nefrologia 2022; 42 Suppl 2:5-132. [PMID: 36503720 DOI: 10.1016/j.nefroe.2022.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 10/26/2021] [Indexed: 06/17/2023] Open
Abstract
This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.
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Affiliation(s)
| | - Marta Crespo
- Nephrology Department, Hospital del Mar, Barcelona, Spain
| | | | | | - Juana Alonso
- Nephrology Department, Hospital Regional Universitario de Málaga, Spain
| | | | | | - Esther González
- Nephrology Department, Hospital Universitario 12 Octubre, Spain
| | | | - Lluis Guirado
- Nephrology Department, Fundacio Puigvert, Barcelona, Spain
| | | | - Jorge Huguet
- RT Surgical Team, Fundació Puigvert, Barcelona, Spain
| | | | - Mireia Musquera
- Urology Department, Hospital Clinic Universitari, Barcelona, Spain
| | - David Paredes
- Donation and Transplantation Coordination Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Ignacio Revuelta
- Nephrology and RT Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Antonio Alcaraz
- Urology Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Manuel Alonso
- Regional Transplantation Coordination, Seville, Spain
| | | | - Gabriel Bernal
- Nephrology Department, Hospital Universitario Virgen del Rocío, Seville, Spain
| | - Alberto Breda
- RT Surgical Team, Fundació Puigvert, Barcelona, Spain
| | - Mercedes Cabello
- Nephrology Department, Hospital Regional Universitario de Málaga, Spain
| | | | - Joan Cid
- Apheresis and Cell Therapy Unit, Haemotherapy and Haemostasis Department, Hospital Clinic Universitari, Barcelona, Spain
| | - Fritz Diekmann
- Nephrology and RT Department, Hospital Clinic Universitari, Barcelona, Spain
| | - Laura Espinosa
- Paediatric Nephrology Department, Hospital La Paz, Madrid, Spain
| | - Carme Facundo
- Nephrology Department, Fundacio Puigvert, Barcelona, Spain
| | | | | | - Miquel Lozano
- Apheresis and Cell Therapy Unit, Haemotherapy and Haemostasis Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | | | | | | | - Eduard Palou
- Immunology Department, Hospital Clinic i Universitari, Barcelona, Spain
| | | | - Lluis Peri
- Urology Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | | | | | - Domingo Hernández
- Nephrology Department, Hospital Regional Universitario de Málaga, Spain
| | | | - Julio Pascual
- Nephrology Department, Hospital del Mar, Barcelona, Spain.
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15
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Ngamvichchukorn T, Ruengorn C, Noppakun K, Thavorn K, Hutton B, Sood MM, Knoll GA, Nochaiwong S. Association Between Pretransplant Dialysis Modality and Kidney Transplant Outcomes: A Systematic Review and Meta-analysis. JAMA Netw Open 2022; 5:e2237580. [PMID: 36264575 PMCID: PMC9585427 DOI: 10.1001/jamanetworkopen.2022.37580] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
IMPORTANCE The benefits and disadvantages of different pretransplant dialysis modalities and their posttransplant outcomes remain unclear in contemporary kidney transplant care. OBJECTIVE To summarize the available evidence of the association of different pretransplant dialysis modalities, including hemodialysis and peritoneal dialysis (PD), with posttransplant outcomes. DATA SOURCES MEDLINE, Embase, PubMed, Cochrane Library, Scopus, CINAHL, and gray literature were searched from inception to March 18, 2022 (updated to April 1, 2022), for relevant studies and with no language restrictions. STUDY SELECTION Randomized clinical trials and nonrandomized observational (case-control and cohort) studies that investigated the association between pretransplant dialysis modality and posttransplant outcomes regardless of age or donor sources (living or deceased) were abstracted independently by 2 reviewers. DATA EXTRACTION AND SYNTHESIS Following Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines, 2 reviewers independently extracted relevant information using a standardized approach. Random-effects meta-analysis was used to estimate pooled adjusted hazard ratio (HR) or odds ratio and 95% CI. MAIN OUTCOMES AND MEASURES Primary outcomes included all-cause mortality, overall graft failure, death-censored graft failure, and delayed graft function. Secondary outcomes included acute rejection, graft vessel thrombosis, oliguria, de novo heart failure, and new-onset diabetes after transplant. RESULTS The study analyzed 26 nonrandomized studies (1 case-control and 25 cohort), including 269 715 patients (mean recipient age range, 14.5-67.0 years; reported proportions of female individuals, 29.4%-66.9%) whose outcomes associated with pretransplant hemodialysis vs pretransplant PD were compared. No significant difference, with very low certainty of evidence, was observed between pretransplant PD and all-cause mortality (13 studies; n = 221 815; HR, 0.92 [95% CI, 0.84-1.01]; P = .08) as well as death-censored graft failure (5 studies; n = 96 439; HR, 0.98 [95% CI, 0.85-1.14]; P = .81). However, pretransplant PD was associated with a lower risk for overall graft failure (10 studies; n = 209 287; HR, 0.96 [95% CI, 0.92-0.99]; P = .02; very low certainty of evidence) and delayed graft function (6 studies; n = 47 118; odds ratio, 0.73 [95% CI, 0.70-0.76]; P < .001; low certainty of evidence). Secondary outcomes were inconclusive due to few studies with available data. CONCLUSIONS AND RELEVANCE Results of the study suggest that pretransplant PD is a preferred dialysis modality option during the transition to kidney transplant. Future studies are warranted to address shared decision-making between health care professionals, patients, and caregivers as well as patient preferences.
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Affiliation(s)
- Tanun Ngamvichchukorn
- Division of Nephrology, Department of Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Chidchanok Ruengorn
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
- Pharmacoepidemiology and Statistics Research Center, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
| | - Kajohnsak Noppakun
- Pharmacoepidemiology and Statistics Research Center, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Kednapa Thavorn
- Pharmacoepidemiology and Statistics Research Center, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
- Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada
- ICES uOttawa, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Brian Hutton
- Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada
- ICES uOttawa, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Manish M. Sood
- Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada
- Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Greg A. Knoll
- Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada
- Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Surapon Nochaiwong
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
- Pharmacoepidemiology and Statistics Research Center, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
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16
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The Role of Donor Sex in Females Undergoing Repeat Kidney Transplant: Does Prior Donor Sex Matter? Transplant Direct 2022; 8:e1352. [PMID: 37077730 PMCID: PMC10109158 DOI: 10.1097/txd.0000000000001352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/11/2022] [Accepted: 05/25/2022] [Indexed: 11/26/2022] Open
Abstract
Female recipients of male donor kidneys are at increased risk for graft failure because of the HY antigen effect. However, whether prior transplant with a male donor impacts subsequent transplant outcomes is unknown. Therefore, the purpose of this study was to determine whether prior male-current male donor sex is associated with an increased risk of graft failure in female recipients. Methods We performed a cohort study of adult female recipients undergoing a second kidney transplant (2000-2017), identified using the Scientific Registry of Transplant Recipients. Using multivariable Cox models, we analyzed the risk of death-censored graft loss (DCGL) if the second transplant was from a male versus female kidney donor, conditional on donor sex at the time of the first transplant. In a secondary analysis, we stratified results by recipient age (>50 or ≤50 y) at the time of retransplant. Results Of 5594 repeat kidney transplants, 1397 (25.0%) developed DCGL. Overall, there was no association between first and second donor sex pairing and DCGL. A prior and current female donor (FD1FD2) posed a higher risk for DCGL in recipients aged >50 y at second transplant (hazard ratio,≤0.67, confidence interval 0.46-0.98, for all other donor combinations), but posed a lower risk if aged ≤50 y at retransplant (hazard ratio, ≥1.37, confidence interval 1.04-1.80, for all other donor combinations). Conclusions Overall, past-current donor sex pairing was not associated with DCGL in female recipients undergoing second kidney transplant; however, the risk with a past and current female donor was increased in older, and decreased in younger, female recipients at retransplant.
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17
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Naesens M, Budde K, Hilbrands L, Oberbauer R, Bellini MI, Glotz D, Grinyó J, Heemann U, Jochmans I, Pengel L, Reinders M, Schneeberger S, Loupy A. Surrogate Endpoints for Late Kidney Transplantation Failure. Transpl Int 2022; 35:10136. [PMID: 35669974 PMCID: PMC9163814 DOI: 10.3389/ti.2022.10136] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 01/18/2022] [Indexed: 12/13/2022]
Abstract
In kidney transplant recipients, late graft failure is often multifactorial. In addition, primary endpoints in kidney transplantation studies seek to demonstrate the short-term efficacy and safety of clinical interventions. Although such endpoints might demonstrate short-term improvement in specific aspects of graft function or incidence of rejection, such findings do not automatically translate into meaningful long-term graft survival benefits. Combining many factors into a well-validated model is therefore more likely to predict long-term outcome and better reflect the complexity of late graft failure than using single endpoints. If conditional marketing authorization could be considered for therapies that aim to improve long-term outcomes following kidney transplantation, then the surrogate endpoint for graft failure in clinical trial settings needs clearer definition. This Consensus Report considers the potential benefits and drawbacks of several candidate surrogate endpoints (including estimated glomerular filtration rate, proteinuria, histological lesions, and donor-specific anti-human leukocyte antigen antibodies) and composite scoring systems. The content was created from information prepared by a working group within the European Society for Organ Transplantation (ESOT). The group submitted a Broad Scientific Advice request to the European Medicines Agency (EMA), June 2020: the request focused on clinical trial design and endpoints in kidney transplantation. Following discussion and refinement, the EMA made final recommendations to ESOT in December 2020 regarding the potential to use surrogate endpoints in clinical studies that aim to improving late graft failure.
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Affiliation(s)
- Maarten Naesens
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Luuk Hilbrands
- Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Rainer Oberbauer
- Department of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | | | - Denis Glotz
- Paris Translational Research Center for Organ Transplantation, Hôpital Saint Louis, Paris, France
| | | | - Uwe Heemann
- Department of Nephrology, Technical University of Munich, Munich, Germany
| | - Ina Jochmans
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Liset Pengel
- Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Marlies Reinders
- Department of Internal Medicine, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Stefan Schneeberger
- Department of General, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Alexandre Loupy
- Paris Translational Research Center for Organ Transplantation, Hôpital Necker, Paris, France
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18
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Recomendaciones para el trasplante renal de donante vivo. Nefrologia 2022. [DOI: 10.1016/j.nefro.2021.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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19
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Impact of the Type of Dialysis on Time to Transplantation: Is It Just a Matter of Immunity? J Clin Med 2022; 11:jcm11041054. [PMID: 35207326 PMCID: PMC8874533 DOI: 10.3390/jcm11041054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/11/2022] [Accepted: 02/16/2022] [Indexed: 01/27/2023] Open
Abstract
Background: Renal transplantation represents the therapeutic gold standard in patients with end stage renal disease (ESRD). Still the role of pre-transplant dialysis in affecting time to transplantation has yet to be determined. We wanted to verify whether the type of renal replacement therapy (hemodialysis vs. peritoneal dialysis) affects time to transplantation and to identify clinical features related to the longer time to transplantation. Methods: We performed a retrospective single-center observational study on patients who had received a transplant in the Bologna Transplant Unit from 1991 to 2019, described through the analysis of digital transplant list documents for sex, age, body mass index (BMI), blood group, comorbidities, underlying disease, serology, type of dialysis, time to transplantation, Panel Reactive Antibodies (PRA) max, number of preformed anti Human Leukocyte Antigens (HLA) antibodies. A p-value < 0.05 was considered statistically significant. Results: In the 1619 patients analyzed, we observed a significant difference in time to transplant, PRA max and Preformed Antibodies Number between patients who received Hemodialysis (HD) and Peritoneal dialysis (PD). Then we performed a multiple regression analysis with all the considered factors in order to identify features that support these differences. The clinical variables that independently and directly correlate with longer time to transplantation are PRA max (p < 0.0001), Antibodies number (p < 0.0001) and HD (p < 0.0001); though AB blood group (p < 0.0001), age (p < 0.003) and PD (p < 0.0001) inversely correlate with time to transplantation. Conclusions: In our work, PD population received renal transplants in a shorter period of time compared to HD and turned out to be less immunized. Considering immunization, the type of dialysis impacts both on PRA max and on anti HLA antibodies.
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20
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Evans RD, Lan JH, Kadatz M, Brar S, Chang DT, McMichael L, Gill J, Gill JS. Use and Outcomes of Induction Therapy in Well-Matched Kidney Transplant Recipients. Clin J Am Soc Nephrol 2022; 17:271-279. [PMID: 35131930 PMCID: PMC8823946 DOI: 10.2215/cjn.09170721] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 11/30/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND AND OBJECTIVES The optimal induction treatment in low-immune risk kidney transplant recipients is uncertain. We therefore investigated the use and outcomes of induction immunosuppression in a low-risk cohort of patients who were well matched with their donor at HLA-A, -B, -DR, -DQB1 on the basis of serologic typing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Our study was an observational study of first adult kidney-only transplant recipients in the United States recorded by the Organ Procurement and Transplant Network. RESULTS Among 2976 recipients, 57% were treated with T cell-depleting antibodies, 28% were treated with an IL-2 receptor antagonist, and 15% were treated without induction. There was no difference in allograft survival, death-censored graft survival, or death with function between patients treated with an IL-2 receptor antagonist and no induction therapy. In multivariable models, patients treated with T cell-depleting therapy had a similar risk of graft loss from any cause, including death (hazard ratio, 1.19; 95% confidence interval, 0.98 to 1.45), compared with patients treated with an IL-2 receptor antagonist or no induction. The findings were consistent in subgroup analyses of Black recipients, patients grouped by calculated panel reactive antibody, and donor source. The incidence of acute rejection at 1 year was low (≤5%) and did not vary between treatment groups. CONCLUSIONS Use of induction therapy with T cell-depleting therapy or IL-2 receptor antagonists in first kidney transplant recipients who are well matched with their donor at the HLA-A, -B, -DR, -DQB1 gene loci is not associated with improved post-transplant outcomes.
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Affiliation(s)
- Rhys D.R. Evans
- Division of Nephrology, Kidney Transplant Program, University of British Columbia, Vancouver, British Columbia, Canada
| | - James H. Lan
- Division of Nephrology, Kidney Transplant Program, University of British Columbia, Vancouver, British Columbia, Canada,Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Matthew Kadatz
- Division of Nephrology, Kidney Transplant Program, University of British Columbia, Vancouver, British Columbia, Canada,Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada
| | - Sandeep Brar
- Division of Nephrology, Kidney Transplant Program, University of British Columbia, Vancouver, British Columbia, Canada
| | - Doris T. Chang
- Providence Health Research Institute, Vancouver, British Columbia, Canada
| | - Lachlan McMichael
- Division of Nephrology, Kidney Transplant Program, University of British Columbia, Vancouver, British Columbia, Canada
| | - Jagbir Gill
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada,Providence Health Research Institute, Vancouver, British Columbia, Canada,Centre for Health Evaluation and Outcomes Sciences, Vancouver, British Columbia, Canada,University of British Columbia School of Population and Public Health, Vancouver, British Columbia, Canada
| | - John S. Gill
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada,Providence Health Research Institute, Vancouver, British Columbia, Canada,Department of Nephrology, Tufts–New England Medical Center, Boston, Massachusetts
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21
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Frequency, reactivity and evolution of human leukocyte antigen and human platelet antigen antibodies in the setting of hematopoietic cell transplantation. Transfus Apher Sci 2021; 61:103301. [PMID: 34774441 DOI: 10.1016/j.transci.2021.103301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 10/18/2021] [Accepted: 10/25/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND AND OBJECTIVES Antibodies (Ab) against HLA and HPA antigens play an important role in HCT. In this prospective study we evaluated prevalence and kinetics of HLA- and HPA-Ab after HCT, including a possible donor-recipient transfer and their clinical relevance in respect to platelet transfusion refractoriness (PTR). MATERIALS AND METHODS Patients were consecutively recruited. Ab were determined by microbead assay technique and a mean fluorescence intensity cut-off of 1,000. RESULTS At baseline, 21 donors (42 %) and 27 patients (54 %) had HLA-Ab with a mean panel reactivity (cPRA) of 34.9 ± 29.4 % and 46.1 ± 36.5 %, respectively. We observed a significant higher number of HLA-Ab specificities in female donors and patients and a predominance of HLA-class I Ab. At day 0 we detected an increase of HLA-Ab (from 526 to 673) and cPRA (55.2 ± 31.9 %). Thirty-six patients (72 %) developed new HLA-Ab, mainly 3 weeks after HCT. In 7 patients an HLA-Ab with the same specificity as detected in the corresponding donor emerged, suggesting a possible transfer from the donor to the recipient. Overall, MFI showed a high variation. Type and number of transfusions were not associated with number and intensity of HLA-Ab (ρ: -0.05 - 0.02). Number of HLA-Ab, cPRA and intensity were not associated with PTR, which occurred in 9 patients (18 %) and none had bleeding WHO > 2. CONCLUSIONS Although a considerable number of patients have and develop HLA-Ab before and early after HCT, we found no association with PTR and bleeding and management should be individualized.
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22
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Cunha APL, Fabreti-Oliveira RA, Lasmar MF, Garcia JC, Vilela TP, Nascimento E. Clinical Outcome of Kidney Transplant Patients on the Allograft Function, Loss, Effects of HLA-DQB1-DSA +, and Graft Survival. Transplant Proc 2021; 53:2188-2196. [PMID: 34420780 DOI: 10.1016/j.transproceed.2021.07.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/16/2021] [Accepted: 07/20/2021] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Matching for HLA-DQB1 molecules and anti-DQ donor-specific antibodies (DSAs) has been less studied to allocate transplants from deceased donors in developed countries. The aim of this study was to evaluate the clinical outcome of 519 kidney transplant recipients on the allograft function, loss, and survival and with emphasis on effects of HLA-DQB1-DSA+ at minimum of 10 years' follow-up. METHODS Five hundred nineteen kidney transplant patients were allocated into 3 groups (G) by immunologic profiles, namely, G1 (SPI-SAB HLA-DQ negative [DQ-]), G2 (SPI-SAB HLA-DQ positive DSA negative [DQ+/DSA-]), and G3 (SPI-SAB HLA-DQ DSA positive [DQ+ DSA+]), and the outcomes were reported until 10 years after transplantation. RESULTS The proportion of rejection episodes was higher in G3 (25.0% and 26.32%, respectively) than in G1 (8.63% and 6.82%, respectively) and G2 (10.0% and 0%, respectively; P = .047 and P = .014, respectively). In G3, 3 patients lost their grafts by antibody-mediated rejection. Patients who received kidneys from deceased donors (G3) showed worse graft survival rates than those from G1 donors (P = .001). Patients from G3 had a 2.18-fold higher risk of graft loss than patients from G1 (P = .028). CONCLUSION Allograft function was worse in G3 than in G2 or G1, and graft losses were more frequent by T-cell-mediated rejection in G1, and graft losses by antibody-mediated rejection were similar in G1 and G3 due to HLA class I (A1, 11 and B 8, 52) and HLA class II by DR7 and DQ 2, 5, 9 DSA, respectively. Allograft survival decreased in patients with HLA-DQB1 DSA. The risk of graft loss was 1.75-fold that in patients who received transplants from living donors.
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Affiliation(s)
- A P L Cunha
- University Hospital of the Faculty of Medical Science, Belo Horizonte, Minas Gerais, Brazil; Faculty of Medical Sciences, Belo Horizonte, Minas Gerais
| | - R A Fabreti-Oliveira
- University Hospital of the Faculty of Medical Science, Belo Horizonte, Minas Gerais, Brazil; IMUNOLAB-Laboratory of Histocompatibility, Belo Horizonte, Minas Gerais, Brazil
| | - M F Lasmar
- University Hospital of the Faculty of Medical Science, Belo Horizonte, Minas Gerais, Brazil; Faculty of Medical Sciences, Belo Horizonte, Minas Gerais
| | - J C Garcia
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais
| | - T P Vilela
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais
| | - E Nascimento
- IMUNOLAB-Laboratory of Histocompatibility, Belo Horizonte, Minas Gerais, Brazil; Institute of Education and Research of the Hospital Santa Casa, Belo Horizonte, Minas Gerais, Brazil.
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23
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Shimabukuro S, Iwasaki K, Kawai S, Shirouzu T, Miwa Y, Iida Y, Nakajima F, Horimi K, Matsuoka Y, Ashimine S, Ishiyama K, Kobayashi T. Improved detection of donor-specific HLA-class II antibody in kidney transplant recipients by modified immunocomplex capture fluorescence analysis. Transpl Immunol 2021; 67:101418. [PMID: 34052300 DOI: 10.1016/j.trim.2021.101418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/25/2021] [Accepted: 05/26/2021] [Indexed: 11/16/2022]
Abstract
Immunocomplex capture fluorescence analysis (ICFA) which basic principle is same as Luminex crossmatch (LXM), could detect donor-specific HLA antibody (DSA). The advantages of ICFA are (i) detection of DSA and (ii) no requirement of viable cells over the flow cytometry crossmatch (FCXM). However, FCXM has been widely used because of its higher sensitivity than ICFA, in particular HLA-class II antibody detection. In this study the accuracy of DSA detection against HLA-class II was investigated by modifying the original method of ICFA. Increment of the sensitivity was found when purified peripheral blood mononuclear cells (PBMCs) were used instead of whole blood. An ICFA-PBMC in addition to FCXM-T/B was conducted for 118 patients before kidney transplantation and 13 patients with de novo DSA against HLA-class II after transplantation. Significantly positive correlation was observed between the values of ICFA-PBMC and DSA mean fluorescence intensity (MFI) targeting class II (p < 0.0001). When the cutoff level of 1.4 was determined by receiver operating characteristic curve analysis, the average DSA MFI was found to be significantly higher in the ICFA-PBMC (class II) positive group comparing to that in the negative group (12,217 vs 3885, p = 0.0027). ICFA-PBMC and optimized cutoff level could provide valid information in cases of suspected DSA.
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Affiliation(s)
- Shuichi Shimabukuro
- Department of Urology, Okinawa Chubu Hospital, 281, Miyazato, Uruma, Okinawa, Japan; Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Kenta Iwasaki
- Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Japan.
| | - Shintaro Kawai
- Wakunaga Pharmaceutical Co, Ltd, Molecular Diagnostics Division, Osaka, Japan
| | - Takayuki Shirouzu
- Wakunaga Pharmaceutical Co, Ltd, Molecular Diagnostics Division, Osaka, Japan
| | - Yuko Miwa
- Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Yusuke Iida
- Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Fumiaki Nakajima
- Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan
| | - Kosei Horimi
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Yutaka Matsuoka
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Satoshi Ashimine
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Kohei Ishiyama
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Takaaki Kobayashi
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
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Chauhan R, Tiwari AK, Rajvanshi C, Mehra S, Saini A, Aggarwal G, Bansal SB, Kher V, Nandi SP. Prevalence of Clinically Significant anti-HLA Antibodies in Renal Transplant Patients: Single-center Report from North India. Indian J Nephrol 2021; 31:240-244. [PMID: 34376937 PMCID: PMC8330640 DOI: 10.4103/ijn.ijn_353_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 12/17/2019] [Accepted: 04/19/2020] [Indexed: 11/05/2022] Open
Abstract
Introduction: Solid organ transplantation is the preferred therapeutic modality of treatment in patients affected by terminal organ failures. Human leukocyte antigens (HLAs) plays an important role in graft survival. In many of the cases of rejection, antibodies are directed against HLA antigens expressed on the cells of the transplanted organ. Pre-transplant compatibility testing involves the use of different methodologies for the determination of anti-HLA antibodies. Luminex single-antigen bead (SAB) assay demonstrates higher sensitivity and specificity in detecting anti-HLA antibodies. The aim of this study was to determine the prevalence of anti-HLA antibodies in pre-transplant work up recipients, planned for renal transplant at a tertiary care center in India. Methods: 1640 patients visiting tertiary care hospital for pre-transplant compatibility testing were screened with complement-dependent micro-lymphocytotoxicity crossmatch (CDC-XM) and flow cytometric crossmatch (FC-XM). The patients positive for either or both screening tests were assayed with the Luminex SAB tests in order to establish defined antigen specificity of the alloantibodies and determining donor-specific antibody (DSA). Results: The two most frequent antibodies identified in each A, B, C locus of HLA class I were -A*24:03 (43.9%), A*25:01 (36.6%), B*57:01 (40.3%), B*15:12 (37.1%), C*17:01 (61.9%), C*07:01 (52.4%) and in DR, DQ DP locus in HLA class II were DRB1*09:01(40.0%), DRB1*14:04(37.6%), DQA1*04:01/DQB1*03:03 (58.4%), DQA1*05:01/DQB1*03:01 (55.1%), DPA1*02:01/DPB1*17:01 (55.0%), DPA1*02:01/DPB1*05:01 (45.0%). Conclusion: This study has found the prevalence and specificity of anti-HLA antibodies in north India.
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Affiliation(s)
- Rajni Chauhan
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India
| | - Aseem Kumar Tiwari
- Department of Transfusion Medicine, Molecular and Transplant Immunology Laboratory, Medanta-The Medicity, Gurugram, Haryana, India
| | - Chhavi Rajvanshi
- Department of Transfusion Medicine, Molecular and Transplant Immunology Laboratory, Medanta-The Medicity, Gurugram, Haryana, India
| | - Simmi Mehra
- Department of Transfusion Medicine, Molecular and Transplant Immunology Laboratory, Medanta-The Medicity, Gurugram, Haryana, India
| | - Abhishek Saini
- Department of Transfusion Medicine, Molecular and Transplant Immunology Laboratory, Medanta-The Medicity, Gurugram, Haryana, India
| | - Geet Aggarwal
- Department of Transfusion Medicine, Molecular and Transplant Immunology Laboratory, Medanta-The Medicity, Gurugram, Haryana, India
| | - Shyam Bihari Bansal
- Department of Nephrology and Transplant Medicine, Medanta-The Medicity, Gurugram, Haryana, India
| | - Vijay Kher
- Department of Nephrology and Transplant Medicine, Medanta-The Medicity, Gurugram, Haryana, India
| | - Shoma Paul Nandi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India
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25
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Chauhan R, Tiwari AK, Rajvanshi C, Mehra S, Aggarwal G, Bansal SB, Kher V. Evaluation of Screening Tests for Pre-Transplant Compatibility Testing in Live-Related Kidney Transplants. INDIAN JOURNAL OF TRANSPLANTATION 2021; 15:99-103. [DOI: 10.4103/ijot.ijot_76_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Introduction:
Pre-transplant compatibility testing involves the use of different methodologies (cell-based and solid phase based) for the determination of anti-human-leukocyte antigen (HLA) antibodies. Implementation of these donor-recipient methods in the screening of patients awaiting transplantation increased their chance of successful graft and patient outcomes.
Materials and Methods:
A total of 1054 patients visiting tertiary care hospitals for pretransplant compatibility testing were screened with cell-based tests; complement-dependent cytotoxicity crossmatch (CDC-XM) and flow cytometric crossmatch (FC-XM). The patients positive for either or both screening tests were suspected to have anti-HLA antibodies. Luminex single-antigen bead (SAB) tests were performed in such patients to determine and identify antibody specificity and establish donor-specific antibody (DSA).
Results:
The study showed a significantly higher sensitivity of the FCXM (94.6%) method when compared with CDC-XM (35.7%), considering the SAB assay as the gold standard technique. The specificity of CDC-XM (100%) was slightly higher than the FC-XM (76.3%). Combination of FC-XM with CDC-XM (17 cases) was 100% sensitive and specific to identify DSA (s). The graft-survival was 94.77% using the proposed algorithm.
Conclusions:
The combination of CDC-XM and FC-XM, along with SAB assay, could be used as a screening algorithm as it is a useful technique in identifying the specificities of alloantibodies, assessment of DSAs. Hence, the presented algorithm can become a new standard for the identification of potential recipients awaiting kidney transplantation in India.
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26
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The HLA System in Transfusion Medicine and Transplantation. Transfus Med 2021. [DOI: 10.1002/9781119599586.ch18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Lan JH, Kadatz M, Chang DT, Gill J, Gebel HM, Gill JS. Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival. Clin J Am Soc Nephrol 2021; 16:275-283. [PMID: 33495290 PMCID: PMC7863647 DOI: 10.2215/cjn.13640820] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/16/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVES Panel reactive antibody informs the likelihood of finding an HLA-compatible donor for transplant candidates, but has historically been associated with acute rejection and allograft survival because testing methods could not exclude the presence of concomitant donor-specific antibodies. Despite new methods to exclude donor-specific antibodies, panel reactive antibody continues to be used to determine the choice of induction and maintenance immunosuppression. The study objective was to determine the clinical relevance of panel reactive antibody in the absence of donor-specific antibodies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Retrospective observational study of kidney allograft survival among 4058 zero HLA-A-, B-, DR-, and DQB1-mismatched transplant recipients without antibodies to donor kidney antigens encoded by these HLA gene loci. RESULTS Among 4058 first and repeat transplant recipients, patients with calculated panel reactive antibody (cPRA) 1%-97% were not at higher risk of transplant failure, compared with patients with cPRA of 0% (death censored graft loss: hazard ratio, 1.07; 95% confidence interval, 0.82 to 1.41). Patients with cPRA ≥98% had a higher risk of graft loss from any cause including death (hazard ratio, 1.39; 95% confidence interval, 1.08 to 1.79) and death censored allograft failure (hazard ratio, 1.78; 95% confidence interval, 1.27 to 2.49). In stratified analyses, the higher risk of graft loss among patients with cPRA ≥98% was only observed among repeat, but not first, transplant recipients. In subgroup analysis, there was no association between cPRA and graft loss among living related transplant recipients. CONCLUSIONS Calculated panel reactive antibody is poorly associated with post-transplant immune reactivity to the allograft in the absence of donor-specific antibody. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_01_25_CJN13640820_final.mp3.
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Affiliation(s)
- James H. Lan
- Vancouver Coastal Health Research Institute, Vancouver, Canada,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada,Division of Nephrology, Kidney Transplant Program, University of British Columbia, Vancouver, Canada
| | - Matthew Kadatz
- Vancouver Coastal Health Research Institute, Vancouver, Canada,Division of Nephrology, Kidney Transplant Program, University of British Columbia, Vancouver, Canada
| | | | - Jagbir Gill
- Division of Nephrology, Kidney Transplant Program, University of British Columbia, Vancouver, Canada,Providence Health Research Institute, Vancouver, Canada,Centre for Health Evaluation and Outcomes Sciences, Vancouver, Canada,School of Population and Public Health, University of British Columbia, Vancouver, Canada
| | | | - John S. Gill
- Division of Nephrology, Kidney Transplant Program, University of British Columbia, Vancouver, Canada,Providence Health Research Institute, Vancouver, Canada,Division of Nephrology, Tufts-New England Medical Center, Boston, Massachusetts
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28
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Aziz F, Tiwari A, Patel H, Chauhan R. Pretransplant histocompatibility testing algorithm: Laboratory and clinical approach in the Indian context. INDIAN JOURNAL OF TRANSPLANTATION 2021. [DOI: 10.4103/ijot.ijot_82_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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29
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Yeung MY. Pre-formed DSA and kidney allograft outcomes. J Bras Nefrol 2020; 42:136-137. [PMID: 32495816 PMCID: PMC7427653 DOI: 10.1590/2175-8239-jbn-2020-0043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 03/01/2020] [Indexed: 01/02/2023] Open
Affiliation(s)
- Melissa Y Yeung
- Brigham and Women's Hospital, Department of Medicine, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
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30
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Senev A, Lerut E, Van Sandt V, Coemans M, Callemeyn J, Sprangers B, Kuypers D, Emonds MP, Naesens M. Specificity, strength, and evolution of pretransplant donor-specific HLA antibodies determine outcome after kidney transplantation. Am J Transplant 2019; 19:3100-3113. [PMID: 31062492 DOI: 10.1111/ajt.15414] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 03/26/2019] [Accepted: 04/18/2019] [Indexed: 01/25/2023]
Abstract
In this cohort study (N = 924), we investigated the evolution and clinical significance of pretransplant donor-specific HLA antibodies (preDSA), detected in the single-antigen beads assay but complement-dependent cytotoxicity crossmatch-negative. Donor specificity of the preDSA (N = 107) was determined by high-resolution genotyping of donor-recipient pairs. We found that in 52% of the patients with preDSA, preDSA spontaneously resolved within the first 3 months posttransplant. PreDSA that persisted posttransplant had higher pretransplant median fluorescence intensity values and more specificity against DQ. Patients with both resolved and persistent DSA had a high incidence of histological picture of antibody-mediated rejection (ABMRh ; 54% and 59% respectively). Patients with preDSA that persisted posttransplant had worse 10-year graft survival compared to resolved DSA and preDSA-negative patients. Compared to cases without preDSA, Cox modeling revealed an increased risk of graft failure only in the patients with persistent DSA, in the presence (hazard ratio [HR] = 8.3) but also in the absence (HR = 4.3) of ABMRh . In contrast, no increased risk of graft failure was seen in patients with resolved DSA. We conclude that persistence of preDSA posttransplant has a negative impact on graft survival, beyond ABMRh . Even in the absence of antibody-targeting therapy, low median fluorescence intensity DSA and non-DQ preDSA often disappear early posttransplantation and are not deleterious for graft outcome.
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Affiliation(s)
- Aleksandar Senev
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.,Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross-Flanders, Mechelen, Belgium
| | - Evelyne Lerut
- Department of Imaging & Pathology, University Hospitals Leuven, Leuven, Belgium
| | - Vicky Van Sandt
- Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross-Flanders, Mechelen, Belgium
| | - Maarten Coemans
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Jasper Callemeyn
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Ben Sprangers
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.,Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Dirk Kuypers
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.,Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Marie-Paule Emonds
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.,Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross-Flanders, Mechelen, Belgium
| | - Maarten Naesens
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.,Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
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Morris AB, Sullivan HC, Krummey SM, Gebel HM, Bray RA. Out with the old, in with the new: Virtual versus physical crossmatching in the modern era. HLA 2019; 94:471-481. [PMID: 31515937 DOI: 10.1111/tan.13693] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 08/26/2019] [Accepted: 09/10/2019] [Indexed: 12/15/2022]
Abstract
The virtual crossmatch (VXM) is gaining acceptance as an alternative approach to assess donor:recipient compatibility prior to transplantation. In contrast to a physical crossmatch, the virtual crossmatch does not require viable donor cells but rather relies on complete HLA typing of the donor and current antibody assessment of the recipient. Thus, the VXM can be performed in minutes which allows for faster transplant decisions thereby increasing the likelihood that organs can be shipped across significant distances yet safely transplanted. Here, we present a brief review of the past 50 years of histocompatibility testing; from the original complement-dependent cytotoxicity crossmatch in 1969 to the new era of molecular HLA typing, solid-phase antibody testing and virtual crossmatching. These advancements have shaped a paradigm shift in our approach to transplantation. That is, foregoing a prospective physical crossmatch in favor of a VXM. In this review, we undertake an in-depth analysis of the pros- and cons- of physical and virtual crossmatching.Finally, we provide objective data on the selected use of the VXM which demonstrate the value of a VXM in lieu of the traditional physical crossmatch for safe and efficient organ transplantation.
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Affiliation(s)
- Anna B Morris
- Department of Surgery, Emory University, Atlanta, Georgia
| | - H C Sullivan
- Department of Pathology, Emory University, Atlanta, Georgia
| | | | - Howard M Gebel
- Department of Pathology, Emory University, Atlanta, Georgia
| | - Robert A Bray
- Department of Pathology, Emory University, Atlanta, Georgia
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Lasmar MF, Dutra RS, Nogueira-Machado JA, Fabreti-Oliveira RA, Siqueira RG, Nascimento E. Effects of immunotherapy induction on outcome and graft survival of kidney-transplanted patients with different immunological risk of rejection. BMC Nephrol 2019; 20:314. [PMID: 31409321 PMCID: PMC6693276 DOI: 10.1186/s12882-019-1497-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 07/26/2019] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND In kidney transplantation, immunotherapy with thymoglobulin (rATG) has been used to down-regulate the patient immune system. rATG is a powerful immunobiologic drug used to deplete lymphocytes to prevent early acute rejection. The aim of this research was to evaluate the effects of immunotherapy by rATG on graft suvival during a 9-year period in kidney-transplanted patients with different immunological profiles. METHODS A sample of 469 patients were allocated into four groups (G) based on immunological risk of rejection: G1, low risk, not sensitized recipients, solid-phase immunoassay with single antigen beads (SPI-SAB) < 10%; G2, medium risk I, sensitized recipients, SPI-SAB ≥ 10 < 50%; G3, medium risk II sensitized (SPI-SAB ≥50%); and G4, high risk, sensitized recipients, SPI-SAB- donor-specific antibody positive (DSA+). Only patients from G3 and G4 received immunotherapy. RESULTS Of 255 patients who received a kidney from a living donor (LD), 42 (16.47%) from all groups (G) had T-cell-mediated rejection (TCMR) and four (G1) lost their grafts, 8 (3.14%) had antibody-mediated rejection (AMR), and two lost their graft in G1 and G4. Of 214 patients who received a kidney from deceased donors (DD), 37 (17.29%) had TCMR with one lost graft in G1. AMR was shown in 13 (6.07%) patients, with three losses observed in G2. Statistical differences between the groups in the 9-year graft survival rate were found only in the comparison of G1 versus G2 (P = 0.005) and G2 versus G4 (P = 0.047) for DD. For LD, no statistical differences were found. CONCLUSION This clinical retrospective study shows that immunotherapy induction was associated with improvement of outcomes, graft function, and survival in patients treated with immunotherapy in comparison with patients who did not received induction therapy. These findings strongly suggest that immunotherapy should be used for all patients transplanted with kidneys from deceased donors.
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Affiliation(s)
- Marcus Faria Lasmar
- University Hospital of the Faculty of Medical Science, Belo Horizonte, Minas Gerais state Brazil
- Institute of Research and Education of the Hospital Santa Casa, Belo Horizonte, Minas Gerais state Brazil
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais State Brazil
| | - Rodrigo Santana Dutra
- University Hospital of the Faculty of Medical Science, Belo Horizonte, Minas Gerais state Brazil
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais State Brazil
| | | | - Raquel A. Fabreti-Oliveira
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais State Brazil
- IMUNOLAB – Laboratory of Histocompatibility, Minas Gerais state, Belo Horizonte, Brazil
| | | | - Evaldo Nascimento
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais State Brazil
- IMUNOLAB – Laboratory of Histocompatibility, Minas Gerais state, Belo Horizonte, Brazil
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DSA-FXM: Accelerated Donor-specific Flow Crossmatch Discriminating Class I and II Antibody Specifically and Only to Donor HLA for Determining True Incompatibility. Transplantation 2019; 104:813-822. [PMID: 31385929 DOI: 10.1097/tp.0000000000002900] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Worldwide, a final crossmatch is the gold standard for determining compatibility between patient and donor before solid organ transplantation and preventing hyperacute rejection. In the absence of autoantibodies, an incompatible crossmatch in a sensitized patient is attributed to mismatched donor HLA. However, current physical crossmatch methods cannot distinguish reactivity to HLA from other clinically irrelevant cell surface targets nor the class of HLA if it is the target. Result interpretation is difficult or impossible when autoantibodies, alloantibodies, or therapeutic antibodies coexist. METHODS Herein, we describe a unique donor-specific flow crossmatch (DSA-FXM) that distinguishes HLA class I or II donor-specific antibody bound to HLA antigens on the donor cell surface in their native conformation that is not impacted by rituximab, anti-thymocyte globulin (after absorption), or autoantibodies. It is HLA specific. RESULTS We compared the results of single-antigen antibody testing, autoreactive and alloreactive flow cytometry crossmatches (FXM) using traditional FXM and our DSA-FXM method from 94 patients (enriched for auto+/allo+ pairs; n = 64) against 110 donors (338 tests) and show that, in our cohort, positive traditional FXM results are not directed to donor HLA 60.25% of the time and negative traditional FXM results are missing HLA donor-specific antibody 36.2% of the time based on the DSA-FXM. CONCLUSIONS We demonstrate that the DSA-FXM is able to define categorically distinct and clinically important HLA antibody profiles in half the time required for the standard FXM, potentially shortening cold ischemia time and providing clinicians with unambiguous essential information regarding HLA compatibility when time is critical.
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Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation. Transplant Direct 2019; 5:e446. [PMID: 31165081 PMCID: PMC6511444 DOI: 10.1097/txd.0000000000000893] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 02/22/2019] [Accepted: 03/07/2019] [Indexed: 02/07/2023] Open
Abstract
Background Many kidney transplant centers in the United States report both HLA class I and II antibodies detected by sensitive solid-phase assays (SPAs) to United Network for Organ Sharing as unacceptable antigens, significantly reducing the compatible donor organ pool and prolonging waiting time for highly sensitized patients. However, the clinical relevance of all detected donor-specific antibodies (DSAs) by SPA is not unequivocal, because fluorescence intensity does not always accurately reflect antibody pathogenicity. Our center does not exclude patients from transplantation based on DSA class II. Methods We performed a retrospective analysis in 179 deceased-donor kidney transplant recipients with solely DSA class II before transplant and patients without DSA and compared graft survival, rejection, and clinical outcomes. Patient survival was also compared with matched controls on the waiting list. Results Patients transplanted with DSA class II showed a clear survival benefit compared with matched patients who remained on dialysis or were waitlisted on dialysis/transplanted at 5 years (100%, 34%, and 73%, respectively). After a mean follow-up of 5.5 years, there was no significant difference in death-censored graft survival between transplanted patients without DSA and those with preformed DSA class II (adjusted HR 1.10; 95% confidence interval, 0.41-2.97), although the incidence of rejection was higher in recipients with DSA class II (adjusted HR 5.84; 95% confidence interval, 2.58-13.23; P < 0.001). Serum creatinine levels at 1, 3, and 5 years posttransplant did not differ between groups. No predictors of rejection were found, although patients who received basiliximab induction therapy had higher incidence of rejection (100%) compared with those who received antithymocyte globulin (52%). Conclusions We conclude that for highly sensitized patients, deceased-donor kidney transplantation with DSA class II yields a survival benefit over prolonged waiting time on dialysis. Instead of listing DSA class II as unacceptable antigens, an individual approach with further immunologic risk assessment is recommended.
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Patients with immunological diseases or on peritoneal dialysis are prone to false positive flow cytometry crossmatch. Hum Immunol 2019; 80:487-492. [PMID: 30904438 DOI: 10.1016/j.humimm.2019.03.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 02/25/2019] [Accepted: 03/19/2019] [Indexed: 11/22/2022]
Abstract
Despite implementation of virtual crossmatches, flow cytometry crossmatches (FCXM) are still used by many transplant centers to determine immunological risk before kidney transplantation. To determine if common profiles of patients prone to false positive FCXM exist, we examined the demographics and native diseases of kidney patients tested with autologous FCXM (n = 480). Improvements to FCXM and cell isolation methods significantly reduced the positive rate from 15.1% to 5.3%. Patients with native diseases considered 'immunological' (vasculitis, lupus, IgA nephropathy) had more positive autologous FCXM (OR = 3.36, p = 0.003) vs. patients with all other diseases. Patients who were tested using our updated method (n = 321) still showed that these immunological diseases were a significant predictor for positive autologous FCXM (OR = 4.79, p = 0.006). Interestingly, patients on peritoneal dialysis (PD) also had significantly more positive autologous FCXM than patients on hemodialysis or waiting for pre-emptive kidney transplants (OR = 3.27, p = 0.02). These findings were confirmed in patients who had false positive allogeneic FCXM. Twenty of 24 (83.3%) patients with false positive allogeneic FCXM tested with updated method either had immunological diseases originally or were on PD. Our findings are helpful when interpreting an unexpected positive FCXM, especially for transplantation from deceased donors.
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Accuracy of the median channel shift in the flow cytometry for predicting complement dependent cytotoxicity crossmatching in kidney transplant candidates. Transpl Immunol 2019; 52:27-31. [DOI: 10.1016/j.trim.2018.10.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 09/13/2018] [Accepted: 10/19/2018] [Indexed: 11/19/2022]
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McCaughan J, Xu Q, Tinckam K. Detecting donor-specific antibodies: the importance of sorting the wheat from the chaff. Hepatobiliary Surg Nutr 2019; 8:37-52. [PMID: 30881964 DOI: 10.21037/hbsn.2019.01.01] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Human leukocyte antigen (HLA) compatibility is very important for successful transplantation of solid organs. In this paper, we focused on the humoral arm of immunity in the clinical setting of organ transplantation: how HLA antibodies develop, how they can be detected, and what they can do to injure organ transplants. Specifically, we explore the technical perspectives of detecting donor-specific antibodies (DSA) in HLA laboratories, and use real-life clinical cases to explain the principles. Currently there are many tools in our HLA antibody detection toolbox: conventional cytotoxicity cross match, flow cross match, and solid phase assays using beads conjugated with single or multiple HLA antigens. Single antigen bead (SAB) assay is the most sensitive tool available for detecting HLA antibodies and assessing the immunological risk for organ transplant. However, there are intrinsic limitations to solid-phase assays and they are prone to both false negativity and importantly, false positivity. Denatured antigens on single antigen beads might be the most prominent source of false positive reactivity, and may have been underestimated by many HLA experts. No single assay is perfect and therefore multiple methods, including the less sensitive assays, should be employed to determine the clinical relevance of detected HLA antibodies. Thoughtful process, including knowledge of HLA systems, cross reactivity, epitopes, and the patient's clinical history should be employed to correctly interpret data. The clinical team should work closely with HLA laboratories to ensure accurate interpretation of information and optimal management of patients before and after organ transplantation.
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Affiliation(s)
- Jennifer McCaughan
- Regional Histocompatibility Laboratory, University Health Network, Toronto, ON, Canada
| | - Qingyong Xu
- Transplant Immunology Lab, London Health Sciences Centre, London, ON, Canada
| | - Kathryn Tinckam
- Regional Histocompatibility Laboratory, University Health Network, Toronto, ON, Canada
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Guillaume N. Improved flow cytometry crossmatching in kidney transplantation. HLA 2018; 92:375-383. [DOI: 10.1111/tan.13403] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 09/11/2018] [Accepted: 09/28/2018] [Indexed: 11/29/2022]
Affiliation(s)
- Nicolas Guillaume
- Department of Histocompatibility Amiens University Medical Center Amiens France
- EA HEMATIM Jules Verne University of Picardie Amiens France
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Gil BC, Kulzer ASS, de Moraes P, Toresan R, da Rosa Vicari A, Dos Santos Fagundes I, Merzoni J, Ewald GM, Cardone JM, Silva FG, Manfro RC, Jobim LF. Comparative analysis of two methods to detect donor-specific anti-HLA antibodies after kidney transplant. Transpl Immunol 2018; 49:7-11. [PMID: 29577967 DOI: 10.1016/j.trim.2018.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 03/16/2018] [Accepted: 03/21/2018] [Indexed: 11/29/2022]
Abstract
Preformed anti-human leukocyte antigen (HLA) antibodies may be present in the blood of kidney transplant candidates. The production of these antibodies may occur in the post-transplant period, with the possible development of donor-specific antibodies (DSA). Luminex-based tests, such as the single antigen (SA) assay and the Luminex crossmatch (Xm-DSA) assay are the most commonly used tools to detect anti-HLA antibodies, due to their high sensitivity and specificity. This cross-sectional study aimed to compare the findings of two methods for the detection of DSAs after kidney transplant: SA and Xm-DSA. A total of 122 patients who underwent deceased donor kidney transplant at Hospital de Clínicas de Porto Alegre were included. The SA assay detected anti-class I HLA DSAs in 17 patients (13.9%) and anti-class II HLA DSAs in 22 patients (19.6%), whereas the Xm-DSA detected DSAs in 18 patients (14.8%) both against class I and class II antigens. There was agreement between the two methods for class I (kappa = 0.66, p = 0.001) and class II (kappa = 0.54, p = 0.025) antigens. The incidence of DSAs as obtained by the SA assay was 15.57%, and the most prevalent DSAs were those against HLA-DR antigens. Patient survival at 3 years was 92%. The two techniques assessed in this study provide important information on the presence of DSAs and may help in the post-transplant patient monitoring and in immunosuppressive strategy.
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Affiliation(s)
- Beatriz Chamun Gil
- Service of Immunology, Hospital de Clínicas de Porto Alegre, Brazil; Graduate Program in Medicine: Surgical Sciences, UFRGS, Brazil.
| | | | | | - Realdete Toresan
- Service of Immunology, Hospital de Clínicas de Porto Alegre, Brazil
| | | | | | - Jóice Merzoni
- Service of Immunology, Hospital de Clínicas de Porto Alegre, Brazil; Graduate Program in Medicine: Surgical Sciences, UFRGS, Brazil
| | | | | | | | - Roberto Ceratti Manfro
- Service of Nephrology, Hospital de Clínicas de Porto Alegre, Brazil; Graduate Program in Medicine: Medical Sciences, UFRGS, Brazil
| | - Luiz Fernando Jobim
- Service of Immunology, Hospital de Clínicas de Porto Alegre, Brazil; Graduate Program in Medicine: Surgical Sciences, UFRGS, Brazil
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Oh D, Kang ES, Yu S, Chun K, Huh W, Jang HR, Cho CW, Lee N, Lee KW, Park H, Park JB, Kim SJ. Case Report of Kidney Paired Donation (KPD) with Desensitization: the Strategy and Experience of 3-Way KPD in Samsung Medical Center. J Korean Med Sci 2018; 33:e39. [PMID: 29349948 PMCID: PMC5773852 DOI: 10.3346/jkms.2018.33.e39] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Accepted: 12/03/2016] [Indexed: 01/10/2023] Open
Abstract
As the need for the organ donation increases, strategies to increase kidney transplantation (KT) through expanded living donation have become essential. These include kidney paired donation (KPD) programs and desensitization in incompatible transplantations. KPD enables kidney transplant candidates with incompatible living donors to join a registry with other incompatible pairs in order to find potentially compatible living donor. Positive cross match and ABO incompatible transplantation has been successfully accomplished in selective cases with several pre-conditionings. Patients who are both difficult-to-match due to broad sensitization and hard-to-desensitize because of donor conditions can often be successfully transplanted through a combination of KPD and desensitization. According to the existing data, KPD can increase the number of KTs from living donors with excellent clinical results. This is also a cost-effective treatment as compared with dialysis and desensitization protocols. We carried out 3-way KPD transplantation with one highly sensitized, positive cross match pair and with two ABO incompatible pairs. Herein we report our first successful 3-way KPD transplantation in a single center. To maximize donor-recipient matching and minimize immunologic risk, KPD programs should use proper algorithms with desensitization to identify optimal donor with simultaneous two-, three- or more complex multi-way exchanges.
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Affiliation(s)
- Dongkyu Oh
- Department of Surgery, Myongji Hospital, Goyang, Korea
| | - Eun Suk Kang
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
| | - Shinae Yu
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyoungsuk Chun
- Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wooseong Huh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hye Ryoun Jang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chan Woo Cho
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nuri Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyo Won Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyojun Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Berm Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Joo Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Althaf MM, El Kossi M, Jin JK, Sharma A, Halawa AM. Human leukocyte antigen typing and crossmatch: A comprehensive review. World J Transplant 2017; 7:339-348. [PMID: 29312863 PMCID: PMC5743871 DOI: 10.5500/wjt.v7.i6.339] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 08/22/2017] [Accepted: 10/17/2017] [Indexed: 02/05/2023] Open
Abstract
Renal transplantation remains the best option for patients suffering from end stage renal disease (ESRD). Given the worldwide shortage of organs and growing population of patients with ESRD, those waitlisted for a transplant is ever expanding. Contemporary crossmatch methods and human leukocyte antigen (HLA) typing play a pivotal role in improving organ allocation and afford better matches to recipients. Understanding crossmatch as well as HLA typing for renal transplantation and applying it in clinical practice is the key step to achieve a successful outcome. Interpretation of crossmatch results can be quite challenging where clinicians have not had formal training in applied transplant immunology. This review aims to provide a worked example using a clinical vignette. Furthermore, each technique is discussed in detail with its pros and cons. The index case is that of a young male with ESRD secondary to Lupus nephritis. He is offered a deceased donor kidney with a 1-0-0 mismatch. His complement dependent cytotoxicity (CDC) crossmatch reported positive for B lymphocyte, but flow cytometry crossmatch (FCXM) was reported negative for both B and T lymphocytes. Luminex-SAB (single antigen bead) did not identify any donor specific antibodies (DSA). He never had a blood transfusion. The positive CDC-crossmatch result is not concordant with DSA status. These implausible results are due to underlying lupus erythematosus, leading to false-positive B-lymphocyte crossmatch as a result of binding immune complexes to Fc-receptors. False positive report of CDC crossmatch can be caused by the underlying autoimmune diseases such as lupus erythematosus, that may lead to inadvertent refusal of adequate kidney grafts. Detailed study of DSA by molecular technique would prevent wrong exclusion of such donors. Based on these investigations this patient is deemed to have "standard immunological risk" for renal transplantation.
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Affiliation(s)
- Mohammed Mahdi Althaf
- Jack Pryor Renal Unit, Norfolk and Norwich University Hospital - NHS Foundation Trust, Norwich NR4 7UY, United Kingdom
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
| | - Mohsen El Kossi
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Doncaster Royal Infirmary, Doncaster DN2 5LT, United Kingdom
| | - Jon Kim Jin
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Nottingham Children Hospital, Nottingham NG7 2UH, United Kingdom
| | - Ajay Sharma
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Royal Liverpool University Hospitals, Liverpool L7 8XP, United Kingdom
| | - Ahmed Mostafa Halawa
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Department of Transplantation Surgery, Sheffield Teaching Hospitals, Sheffield S5 7AU, United Kingdom
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Donor-specific HLA antibodies in predicting crossmatch outcome: Comparison of three different laboratory techniques. Transpl Immunol 2017; 46:23-28. [PMID: 29157597 DOI: 10.1016/j.trim.2017.11.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 11/09/2017] [Accepted: 11/16/2017] [Indexed: 01/18/2023]
Abstract
The virtual crossmatch, which is based on single antigen bead technology, is used in the prediction of crossmatch results. However, this assay differs in sensitivity and specificity from crossmatch methods. In our study, the results of physical crossmatches, performed with three different methods, were assessed against virtual crossmatch results. The aim was to determine the potential cut-off values for donor specific antibodies (DSA) that would predict the crossmatch results obtained by different methods. The results of different crossmatch techniques were correlated with the virtual crossmatch. The receiver operating characteristic (ROC) analysis revealed the Flow cytometric crossmatch (FCXM) and Luminex crossmatch (LXM) to be the most accurate, with area under curve (AUC) values of 0.861 and 0.805, respectively. While we found that the virtual crossmatch correlated well with all the crossmatch results, FCXM produced the best results (83% of the DSA detected). LXM outperformed the other tests in terms of the accuracy in separating class II DSA.
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Cytolytic Induction Therapy Improves Clinical Outcomes in African-American Kidney Transplant Recipients. Ann Surg 2017; 266:450-456. [PMID: 28654544 DOI: 10.1097/sla.0000000000002366] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
OBJECTIVE Determine the impact of cytolytic versus IL-2 receptor antibody (IL-2RA) induction on acute rejection, graft loss and death in African-American (AA) kidney transplant (KTX) recipients. BACKGROUND AAs are underrepresented in clinical trials in transplantation; thus, there is controversy regarding the optimal choice of perioperative antibody induction in KTX to improve outcomes. METHODS National cohort study using US transplant registry data from January 1, 2000 to December 31, 2009 in adult solitary AA KTX recipients, with at least 5 years of follow-up. Multivariable logistic and Cox regression were utilized to assess the outcomes of acute rejection, graft loss, and mortality, with interaction terms to assess effect modification. RESULTS Twenty-five thousand eighty-four adult AAs receiving solitary KTX were included, 16,927 (67.5%) received cytolytic induction and 8157 (32.5%) received IL-2RA induction. After adjustment for recipient sociodemographics, donor, and transplant characteristics, the use of cytolytic induction therapy reduced the risk of acute rejection by 32% (OR 0.68, 0.62-0.75), graft loss by 9% (HR 0.91, 0.86-0.97), and death by 12% (HR 0.88, 0.83-0.94). There were a number of significant effect modifiers, including public insurance, panel reactive antibody, delayed graft function, and steroid withdrawal; in these groups, cytolytic induction substantially improved clinical outcomes. CONCLUSIONS These data demonstrate that cytolytic induction therapy, as compared with IL-2RA, reduces the risk of rejection, graft loss, and death in adult AA KTX recipients, particularly in those who are sensitized, receive public insurance, develop delayed graft function, or undergo steroid withdrawal.
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Liu P, Souma T, Wei AZS, Xie X, Luo X, Jin J. Personalized Peptide Arrays for Detection of HLA Alloantibodies in Organ Transplantation. J Vis Exp 2017. [PMID: 28930983 DOI: 10.3791/56278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
In organ transplantation, the function and longevity of the graft critically rely on the success of controlling immunological rejection reactivity against human leukocyte antigens (HLA). Histocompatibility guidelines are based on laboratory tests of anti-HLA immunity, which presents either as pre-existing or de novo generated HLA antibodies that constitute a major transplantation barrier. Current tests are built on a single-antigen beads (SAB) platform using a fixed set of ~100 preselected recombinant HLA antigens to probe transplant sera. However, in humans there exist a far greater variety of HLA types, with no two individuals other than identical twins who can share the same combination of HLA sequences. While advanced technologies for HLA typing and direct sequencing can precisely capture any mismatches in DNA sequence between a donor's and recipient's HLA, the SAB assay, due to its limited variety in sequence representation, is unable to precisely detect alloantibodies specifically against the donor HLA mismatches. We sought to develop a complementary method using a different technology to detect and characterize anti-donor HLA antibodies on a personalized basis. The screening tool is a custom peptide array of donor HLA-derived sequences for probing post-transplant sera of the organ recipient to assess the risk for antibody-mediated rejection. On a single array for one donor-recipient pair, up to 600 unique peptides are made based on the donor's HLA protein sequences, each peptide carrying at least one mismatched residue in a 15-amino acid sequence. In our pilot experiments to compare antigen patterns for pre- and post-transplant sera on these arrays, we were able to detect anti-HLA signals with the resolution that also allowed us to pinpoint the immune epitopes involved. These personalized antigen arrays allow high-resolution detection of donor-specific HLA epitopes in organ transplantation.
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Affiliation(s)
- Pan Liu
- Division of Nephrology and Hypertension, and the Center for Kidney Research and Therapeutics at the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine
| | - Tomokazu Souma
- Division of Nephrology and Hypertension, and the Center for Kidney Research and Therapeutics at the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine
| | - Andrew Zu-Sern Wei
- Division of Nephrology and Hypertension, and the Center for Kidney Research and Therapeutics at the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine
| | - Xueying Xie
- School of Biological Sciences and Medical Engineering, Southeast University
| | - Xunrong Luo
- Surgery-Organ Transplantation, Northwestern University Feinberg School of Medicine
| | - Jing Jin
- Division of Nephrology and Hypertension, and the Center for Kidney Research and Therapeutics at the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine;
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Mehrotra S, Sharma RK, Mayya M, Gupta A, Prasad N, Kaul A, Bhadauria DS. Luminex Solid-Phase Crossmatch for De Novo Donor-Specific Antibodies in Living-Donor Related Transplants. EXP CLIN TRANSPLANT 2017; 15:394-399. [PMID: 28447925 DOI: 10.6002/ect.2016.0178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES There are no reports of de novo donor-specific antibody monitoring by a low-cost solid-phase crossmatch assay using donor lysate after renal transplant. MATERIALS AND METHODS We prospectively evaluated 121 complement-dependant cytotoxicity crossmatch-negative living-donor kidney transplant recipients for development of de novo donor-specific antibodies (class I and II HLA) by solid-phase crossmatch Luminex assay after transplant. RESULTS Of 121 recipients in our study group, 26 (21.5%) developed de novo donor-specific antibody within 3 months after transplant. Fifteen (58%) of these 26 recipients developed class II de novo donor-specific antibody, 8 patients (30%) developed class I, and 3 (12%) developed both class I and class II. Of the remaining 95 patients (79%) who did not develop de novo donor-specific antibody, 6 (33.3%) had antibody-mediated rejection with glomerulitis (2 with C4d-positive disease). Donor-specific antibody was detected by Luminex solid-phase crossmatch in 18 patients (5 with class I, 11 with class II, and 2 with both class I and II), all with no evidence of clinical rejection. Development of de novo donor-specific antibody detected by solid-phase crossmatch was associated with more acute rejection (31% in de novo donor-specific antibody-positive group versus 19% in the negative group). The positive group had more antibody-mediated rejection (75% of acute rejections), whereas only 33.3% of acute rejections in the negative group were antibody-mediated rejection. Of 12 patients with antibody-mediated rejection, 9 were C4d negative (75%) and were diagnosed by donor-specific antibody positivity detected by solid-phase cros?match testing and histologic findings. The use of donor lysate in solid-phase crossmatch assays is more economical than the single-antigen bead Luminex assay (per test cost of US $45.20 vs $403.20).
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Affiliation(s)
- Sonia Mehrotra
- From the Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
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Fasano RM, Sullivan HC, Bray RA, Gebel HM, Meyer EK, Winkler AM, Josephson CD, Stowell SR, Sandy Duncan A, Roback JD. Genotyping Applications for Transplantation and Transfusion Management: The Emory Experience. Arch Pathol Lab Med 2017; 141:329-340. [PMID: 28234571 DOI: 10.5858/arpa.2016-0277-sa] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Current genotyping methodologies for transplantation and transfusion management employ multiplex systems that allow for simultaneous detection of multiple HLA antigens, human platelet antigens, and red blood cell (RBC) antigens. The development of high-resolution, molecular HLA typing has led to improved outcomes in unrelated hematopoietic stem cell transplants by better identifying compatible alleles of the HLA-A, B, C, DRB1, and DQB1 antigens. In solid organ transplantation, the combination of high-resolution HLA typing with solid-phase antibody identification has proven of value for highly sensitized patients and has significantly reduced incompatible crossmatches at the time of organ allocation. This database-driven, combined HLA antigen/antibody testing has enabled routine implementation of "virtual crossmatching" and may even obviate the need for physical crossmatching. In addition, DNA-based testing for RBC antigens provides an alternative typing method that mitigates many of the limitations of hemagglutination-based phenotyping. Although RBC genotyping has utility in various transfusion settings, it has arguably been most useful for minimizing alloimmunization in the management of transfusion-dependent patients with sickle cell disease or thalassemia. The availability of high-throughput RBC genotyping for both individuals and large populations of donors, along with coordinated informatics systems to compare patients' antigen profiles with available antigen-negative and/or rare blood-typed donors, holds promise for improving the efficiency, reliability, and extent of RBC matching for this population.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - John D Roback
- From the Center for Transfusion and Cellular Therapies (Drs Fasano, Sullivan, Meyer, Winkler, Josephson, Stowell, Duncan, and Roback) and the Department of Pathology and Laboratory Medicine (Drs Fasano, Sullivan, Bray, Gebel, Meyer, Winkler, Josephson, Stowell, Duncan, and Roback), Emory University School of Medicine, Atlanta, Georgia; and the Department of Transfusion, Tissue, and Apheresis, Children's Healthcare of Atlanta, Atlanta (Drs Fasano, Meyer, and Josephson). Dr Meyer is now with the Department of Pathology, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus
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Nascimento E, Lucas-Junior FM, Fabreti-Oliveira RA, Vilela B, Tavora ERF, Silva JPL, Salomão-Filho A. Kidney Transplantation With Ultralong-Term (42 Years) Survival of a 100-Year-Old Graft. Transplant Proc 2016; 48:3079-3084. [PMID: 27932151 DOI: 10.1016/j.transproceed.2016.02.064] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Accepted: 02/18/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND In kidney transplantation, long-term graft survival has improved over the last few decades. Study to understand ultralong-term graft survival with graft functioning is rare, but a few researchers have tried to explain the factors involved in long-term graft survival. In this report, we explore the predictive factors that can be involved in ultralong-term graft survival. MATERIAL AND METHODS Immunologic evaluations of the patients were performed using crossmatch (XM), serological, and high-resolution HLA typing for 8 loci. A transplant recipient was treated with azathioprine as immunosuppressive monotherapy for 42 years. Donor-specific antibodies (DSAs) were identified using panel reactive antibody single antigen beads (PRA-SAB) followed by EpVix and Matchmaker epitope analysis to define the immunogenic mismatch eplets. RESULTS The patient and donor were haploidentical for 7 loci and identical at the HLA-DPA1* locus. Among 61 identified eplet mismatches, DSAs were not detected against 59 eplets after 42 years of exposure to the patient's immune system with the exceptions of antibodies against the public eplets 9Y and 9YL from allele HLA-DPB1*03:01, and the transplanted kidney exhibited preserved structures. CONCLUSION The transplanted kidney has the preserved structure based on magnetic resonance imaging, the 2 DSAs were not deleterious to the graft until now, and the eplet mismatches were considered acceptable. The patient is in good clinical condition living with a 100-year-old graft, a serum creatinine level of 1.5 mg/dL, and an estimated glomerular filtration rate of 50 mL/1.72 m2.
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Affiliation(s)
- E Nascimento
- Kidney Transplantation Center, Clinical Hospital, Belo Horizonte, Minas Gerais, Brazil; Institute of Medical Sciences, Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil; IMUNOLAB-Laboratory of Histocompatibility and Immunogenetic, Belo Horizonte, Minas Gerais, Brazil.
| | - F M Lucas-Junior
- Kidney Transplantation Center, Clinical Hospital, Belo Horizonte, Minas Gerais, Brazil
| | - R A Fabreti-Oliveira
- Institute of Medical Sciences, Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil; IMUNOLAB-Laboratory of Histocompatibility and Immunogenetic, Belo Horizonte, Minas Gerais, Brazil
| | - B Vilela
- IMUNOLAB-Laboratory of Histocompatibility and Immunogenetic, Belo Horizonte, Minas Gerais, Brazil
| | - E R F Tavora
- Kidney Transplantation Center, Clinical Hospital, Belo Horizonte, Minas Gerais, Brazil
| | - J P L Silva
- Kidney Transplantation Center, Clinical Hospital, Belo Horizonte, Minas Gerais, Brazil
| | - A Salomão-Filho
- Kidney Transplantation Center, Clinical Hospital, Belo Horizonte, Minas Gerais, Brazil
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