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Aspectos técnicos y clínicos de la prueba cruzada de histocompatibilidad en el trasplante de órganos sólidos. BIOMÉDICA 2022; 42:391-413. [PMID: 35867930 PMCID: PMC9467682 DOI: 10.7705/biomedica.6255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Indexed: 11/21/2022]
Abstract
La presencia de anticuerpos dirigidos contra los antígenos leucocitarios humanos (Human Leukocyte Antigens, HLA) que se expresan en las células del donante, es uno de los factores de riesgo más importantes asociados con las complicaciones clínicas después del trasplante. La prueba cruzada es una de las pruebas de histocompatibilidad más eficaces para la detección de anticuerpos específicos contra el donante en los receptores de injertos. En los primeros métodos de la prueba cruzada, se utilizaba la citotoxicidad dependiente del complemento, que es útil para detectar dichos anticuerpos responsables del rechazo hiperagudo del injerto, pero carece de la sensibilidad adecuada. Por ello, se desarrollaron métodos de pruebas cruzadas más sensibles, entre ellas, la prueba cruzada por citometría de flujo que hoy se considera el método preferido. En este artículo se revisa la evolución de la prueba cruzada y los factores más importantes que deben tenerse en cuenta al realizarla y al interpretar los resultados de esta prueba fundamental para la supervivencia a largo plazo del injerto.
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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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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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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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Positive Cytotoxic Crossmatch Predicts Delayed Neutrophil Engraftment in Allogeneic Hematopoietic Cell Transplantation from HLA-Mismatched Related Donors. Biol Blood Marrow Transplant 2017; 23:1895-1902. [DOI: 10.1016/j.bbmt.2017.06.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Accepted: 06/28/2017] [Indexed: 02/08/2023]
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Increase of allosensitization after a kidney graft failure: Predictors and effect on retransplantation outcomes. Nefrologia 2017; 37:397-405. [PMID: 28576438 DOI: 10.1016/j.nefro.2016.11.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 10/14/2016] [Accepted: 11/17/2016] [Indexed: 01/16/2023] Open
Abstract
Patients who are candidates for a second kidney transplant (SKT) frequently have a higher level of panel reactive antibodies (PRA). We assessed the allosensitisation change after a first graft failure (GF), its predictors and impact on retransplantat outcomes. We retrospectively selected 140 adult patients who received a SKT. Recipient and donor characteristics were analyzed. We defined the delta PRA (dPRA) as the difference between peak PRA before the SKT and first one (cohort median value=+10%). Logistic regression analysis was used to determine risk factors for dPRA≥10% and acute rejection (AR) in the SKT. Univariable and multivariable Cox analysis was applied to assess independent predictors of second GF. Risk factors for dPRA≥10% at SKT were AR (OR=2.57; P=0.022), first graft survival <1 year (OR=2.47; P=0.030) and ABDR HLA mismatch (OR=1.38 per each mismatch; P=0.038). AR in the SKT was associated with dPRA≥10% (OR=2.79; P=0.047). Induction with a lymphocyte-depleting agent had a protective effect (OR=0.23; P=0.010). SKT survival was lower (P=0.008) in patients with a dPRA≥10% (75.6%, 60.5% in dPRA≥10%; 88.6%, 88.6% in dPRA<10% patients at 5 and 10 years, post-transplant respectively). Multivariable Cox regression showed that dPRA≥10% (HR=2.38, P=0.042), delayed graft function (HR=2.82, P=0.006) and AR (HR=3.30, P=0.001) in the SKT were independent predictors of retransplant failure. This study shows that an increased allosensitisation at retransplant was associated with the degree of HLA mismatch and led to poorer outcomes. De-emphasis of HLA matching in current allocation policies may be undesirable, particularly in patients with a higher chance of needing a SKT.
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Callus R, Buttigieg J, Anastasi AA, Halawa A. Basic concepts in kidney transplant immunology. Br J Hosp Med (Lond) 2017; 78:32-37. [PMID: 28067566 DOI: 10.12968/hmed.2017.78.1.32] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Advances in the field of immunohistocompatibility and immunogenetics have been crucial for improvements in kidney transplant outcomes. This review provides a practical outline of these important breakthroughs for the general physician, at a time when demand for kidney transplants is increasing.
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Affiliation(s)
- Roberta Callus
- Resident Specialist in Nephrology and General Medicine, Division of Nephrology, Department of Medicine, Mater Dei Hospital, Msida MSD2090, Malta and Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool
| | - Jesmar Buttigieg
- Resident Specialist, Division of Nephrology, Department of Medicine, Mater Dei Hospital, Malta and Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool
| | | | - Ahmed Halawa
- Consultant Transplant Surgeon, Sheffield Teaching Hospitals, Sheffield and Honorary Senior Lecturer, Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool
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Reynolds BC, Tinckam KJ. Sensitization assessment before kidney transplantation. Transplant Rev (Orlando) 2017; 31:18-28. [DOI: 10.1016/j.trre.2016.10.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 10/05/2016] [Indexed: 01/28/2023]
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Abstract
This review paper discusses the impact of de novo donor-specific antibodies (DSA) to donor HLA antigens in kidney transplantation and summarizes the benefits and challenges that exist with DSA monitoring. Post-transplant DSA is associated with worse allograft outcomes and its detection may precede or coincide with clinical, biochemical, and histologic allograft dysfunction. There are no absolute features of DSA testing results that perfectly discriminate between states of disease and health. In a state of antibody-associated graft dysfunction, removal or reduction in DSA may only provide clinical benefit for some. Furthermore, various factors influence test results, and detection of HLA antibodies must be interpreted within the appropriate clinical and laboratory context. The utility of DSA monitoring is further affected by the limited effectiveness of treatment for antibody-mediated rejection. Although DSA monitoring is potentially beneficial in some circumstances, the optimal screening and treatment strategies are still to be defined.
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In vivo heat inactivation of serum can distinguish false positive cross matches in renal transplants. Int J Artif Organs 2016; 39:63-7. [PMID: 26953900 DOI: 10.5301/ijao.5000470] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2016] [Indexed: 11/20/2022]
Abstract
INTRODUCTION Renal transplants have traditionally been performed despite positive cross match if results are presumptively due to IgM antibodies. False positives have been distinguishable from true positives by dithiothreitol or dithioerythritol treatment to inactivate IgM antibodies. Heat inactivation, which renders the antibodies inactive, is an alternative to chemical amelioration. METHODS We retrospectively evaluated clinical outcomes of patients who had positive cross matches presumed to be falsely positive as determined by treatment with heat inactivation compared to controls with negative cross matches over a six-year period. A total of 414 transplanted patients had available cross match data: 355 with a negative cross match and 59 with a positive cross match rendered negative after heat inactivation. Serum creatinine was reviewed at 6, 12 and 24 months posttransplant. RESULTS Graft function was considered stable at 12 and 24 months post-transplant if the change in creatinine compared to the 6-month value was >0.5 mg/dL. Repeated and nonrepeated measures analysis showed equivalence in the change in sCr from 6 to 12 (p = 0.525) and from 6 to 24 months (p = 0.752). Kaplan-Meier curves to evaluate graft survival demonstrated no significant difference in function over 24 months. Curves were censored for patient death, treated as death with functioning (p = 0.48) and nonfunctioning (p = 0.64) grafts. DISCUSSIONS We have demonstrated comparable long-term function and survival for living donor renal transplants using heat inactivation to detect false positive cross matches. This simple and cost-effective method can be used to safely evaluate histocompatibility for living donor renal transplant recipients.
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Zachary AA, Leffell MS. Desensitization for solid organ and hematopoietic stem cell transplantation. Immunol Rev 2014; 258:183-207. [PMID: 24517434 PMCID: PMC4237559 DOI: 10.1111/imr.12150] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Revised: 10/24/2013] [Accepted: 11/04/2013] [Indexed: 12/25/2022]
Abstract
Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft.
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Affiliation(s)
- Andrea A Zachary
- Department of Medicine, Division of Immunogenetics and Transplantation Immunology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Trébern-Launay K, Foucher Y, Giral M, Legendre C, Kreis H, Kessler M, Ladrière M, Kamar N, Rostaing L, Garrigue V, Mourad G, Morelon E, Soulillou JP, Dantal J. Poor long-term outcome in second kidney transplantation: a delayed event. PLoS One 2012; 7:e47915. [PMID: 23110130 PMCID: PMC3479120 DOI: 10.1371/journal.pone.0047915] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2012] [Accepted: 09/18/2012] [Indexed: 01/16/2023] Open
Abstract
Background Old studies reported a worse outcome for second transplant recipient (STR) than for first transplant recipient (FTR) mainly due to non-comparable populations with numbers confounding factors. More recent analysis, based on improved methodology by using multivariate regressions, challenged this generally accepted idea: the poor prognosis for STR is still under debate. Methodology To assess the long-term patient-and-graft survival of STR compared to FTR, we performed an observational study based on the French DIVAT prospective cohort between 1996 and 2010 (N = 3103 including 641 STR). All patients were treated with a CNI, an mTOR inhibitor or belatacept in addition to steroids and mycophenolate mofetil for maintenance therapy. Patient-and-graft survival and acute rejection episode (ARE) were analyzed using Cox models adjusted for all potential confounding factors such as pre-transplant anti-HLA immunization. Results We showed that STR have a higher risk of graft failure than FTR (HR = 2.18, p = 0.0013) but that this excess risk was observed after few years of transplantation. There was no significant difference between STR and FTR in the occurrence of either overall ARE (HR = 1.01, p = 0.9675) or steroid-resistant ARE (HR = 1.27, p = 0.4087). Conclusions The risk of graft failure following second transplantation remained consistently higher than that observed in first transplantation after adjusting for confounding factors. The rarely performed time-dependent statistical modeling may explain the heterogeneous conclusions of the literature concerning second transplantation outcomes. In clinical practice, physicians should not consider STR and FTR equally.
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Affiliation(s)
- Katy Trébern-Launay
- Institut de Transplantation Urologie Néphrologie (ITUN), Inserm U643, CHU Hôtel Dieu, Nantes, France
- Université de Nantes, EA4275 ‘Biostatistique, Recherche Clinique et Mesures Subjectives en Santé’, Nantes, France
| | - Yohann Foucher
- Institut de Transplantation Urologie Néphrologie (ITUN), Inserm U643, CHU Hôtel Dieu, Nantes, France
- Université de Nantes, EA4275 ‘Biostatistique, Recherche Clinique et Mesures Subjectives en Santé’, Nantes, France
| | - Magali Giral
- Institut de Transplantation Urologie Néphrologie (ITUN), Inserm U643, CHU Hôtel Dieu, Nantes, France
| | - Christophe Legendre
- Service de Transplantation Rénale et de Soins Intensifs, Hôpital Necker, APHP, Paris, France
- Universités Paris Descartes et Sorbonne Paris Cité, Paris, France
| | - Henri Kreis
- Service de Transplantation Rénale et de Soins Intensifs, Hôpital Necker, APHP, Paris, France
| | - Michèle Kessler
- Service de Transplantation Rénale, CHU Brabois, Nancy, France
| | - Marc Ladrière
- Service de Transplantation Rénale, CHU Brabois, Nancy, France
| | - Nassim Kamar
- Service de Néphrologie, HTA, Dialyse et Transplantation d'Organes, CHU Rangueil, Toulouse, France
- Université Paul Sabatier, Toulouse, France
| | - Lionel Rostaing
- Service de Néphrologie, HTA, Dialyse et Transplantation d'Organes, CHU Rangueil, Toulouse, France
- Université Paul Sabatier, Toulouse, France
| | - Valérie Garrigue
- Service de Néphrologie-Transplantation, Hôpital Lapeyronie, Montpellier, France
| | - Georges Mourad
- Service de Néphrologie-Transplantation, Hôpital Lapeyronie, Montpellier, France
| | - Emmanuel Morelon
- Service de Néphrologie, Transplantation et Immunologie Clinique, Hôpital Edouard Herriot, Lyon, France
| | - Jean-Paul Soulillou
- Institut de Transplantation Urologie Néphrologie (ITUN), Inserm U643, CHU Hôtel Dieu, Nantes, France
- * E-mail:
| | - Jacques Dantal
- Institut de Transplantation Urologie Néphrologie (ITUN), Inserm U643, CHU Hôtel Dieu, Nantes, France
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Abstract
For most solid organ and selected stem cell transplants, antibodies against mismatched HLA antigens can lead to early and late graft failure. In recognition of the clinical significance of these antibodies, HLA antibody identification is one of the most critical functions of histocompatibility laboratories. Early methods employed cumbersome and insensitive complement-dependent cytotoxicity assays with a visual read-out. A little over 20 years ago flow cytometry entered the realm of antibody detection with the introduction of the flow cytometric crossmatch. Cytometry's increased sensitivity and objectivity quickly earned it popularity as a preferred crossmatch method especially for sensitized recipients. Although a sensitive method, the flow crossmatch was criticized as being "too sensitive" as false positive reactions were a know drawback. In part, the shortcomings of the flow crossmatch were due to the lack of corresponding sensitive and specific HLA antibody screening assays. However, in the mid 1990s, solid phase assays, capable of utilizing standard flow cytometers, were developed. These assays used microparticles coated with purified HLA molecules. Hence, the era of solid-phase, microparticle technology for HLA antibody detection was born permitting the sensitive and specific detection of HLA antibody. It was now possible to provide better correlation between HLA antibody detection and the flow cytometric crossmatch. This flow-based technology was soon followed by adaptation to the Luminex platform permitting a mutltiplexed approach for the identification and characterization of HLA antibodies. It is hoped that these technologies will ultimately lead to the identification of parameters that best correlate with and/or predict transplant outcomes.
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Murphey CL, Forsthuber TG. Trends in HLA antibody screening and identification and their role in transplantation. Expert Rev Clin Immunol 2010; 4:391-9. [PMID: 20476928 DOI: 10.1586/1744666x.4.3.391] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
HLA testing has been a staple in transplantation since the recognition that antibodies, directed against lymphocytes, were associated with allograft failure. This seminal finding led to the discovery of the MHC and the appreciation of the importance of HLA testing in transplantation. Early approaches focused on the importance of HLA matching, and were an important aspect of deceased organ donor allocation. More recently, and as a direct result of improvements in immunosuppression, there has been a movement away from 'matching' as the driving force in organ allocation. By contrast, we are now challenged with selecting donor-recipient pairs based on acceptable mismatches. For patients devoid of HLA antibodies, this is not an issue. However, for patients with HLA alloantibodies, that is, the sensitized patient, we face significant challenges in assessing the repertoire of the HLA antibody reactivity they possess. Over the past several years, significant advances in HLA antibody detection have occurred. Solid-phase, multiplex testing platforms have replaced traditional cell-based assays, and have provided better sensitivity and specificity in antibody detection. As a direct result of improved antibody identification, many programs are moving into the realm of the 'virtual crossmatch'. The virtual crossmatch has proven to be successful in renal, cardiac and lung transplantation, and has resulted in a greater percentage of sensitized patients gaining access to transplantation. This review will be devoted to highlighting the latest developments in antibody assessments and discussing their utilization in transplant testing.
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Affiliation(s)
- Cathi L Murphey
- University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA.
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Haririan A, Nogueira J, Kukuruga D, Schweitzer E, Hess J, Gurk-Turner C, Jacobs S, Drachenberg C, Bartlett S, Cooper M. Positive cross-match living donor kidney transplantation: longer-term outcomes. Am J Transplant 2009; 9:536-42. [PMID: 19191764 DOI: 10.1111/j.1600-6143.2008.02524.x] [Citation(s) in RCA: 112] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The long-term graft outcomes after positive cross-match (PXM) living donor kidney transplantation (LDKT) are unknown and the descriptive published data present short-medium term results. We conducted a retrospective cohort study of LDKT with PXM by flow cytometry performed at our center during February 1999 to October 2006, compared to a control group, matched 1:1 for age, sex, race, retransplantation and transplant year. The PXM group was treated with a course of plasmapheresis/low-dose intravenous immunoglobulin (IVIg) preoperatively, and OKT3 or thymoglobulin induction. Both groups (n = 41 each) were comparable except for duration of end-stage renal disease (ESRD), induction, HLA mismatch and panel-reactive antibody (PRA). During the period of up to 9 years, 14 PXM and 7 controls lost their grafts (p < 0.04). Graft survival rates at 1 and 5 years were 89.9% and 69.4% for PXM group and 97.6% and 80.6% for the controls, respectively. PXM was associated with higher risk of graft loss (HR 2.6, p = 0.04; 95%CI 1.03-6.4) (t(1/2)= 6.8 years), but not with patient survival (HR 1.96, p = 0.29; 95%CI 0.6-7.0) or 1-year serum creatinine (beta= 0.06, p = 0.59 for ln (SCr); 95% CI -0.16 to 0.28). These results suggest that despite the favorable short-term results of PXM LDKT after PP/IVIg conditioning, medium-long-term outcomes are notably worse than expected, perhaps comparable to non-ECD deceased donor kidney transplantation (KT).
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Affiliation(s)
- A Haririan
- Department of Medicine, University of MAryland School of Medicine, Baltimore, MD, USA.
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Wang D, Xu TZ, Chen JH, Wu WZ, Yang SL, Lin WH, Cai JQ, Tan JM. Factors influencing second renal allograft survival: a single center experience in China. Transpl Immunol 2008; 20:150-4. [PMID: 18848988 DOI: 10.1016/j.trim.2008.09.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2008] [Revised: 09/11/2008] [Accepted: 09/18/2008] [Indexed: 11/19/2022]
Abstract
Second renal transplants are historically associated with a poor prognosis. The aim of the present study was to assess long-term survival of second renal grafts from deceased donors performed at our center and to analyze risk factors associated with long-term graft outcome. Sixty-five second renal grafts were enrolled into this study, and compared to primary ones performed during the same period. Kaplan-Meier curve showed a graft survival rate of 89.2% at 1 year, 80% at 3 years, and 63.1% at 5 years, which were similar to that of primary graft. Univariate analysis showed that time to first graft loss, cold ischaemia time, HLA mismatch, primary maintenance immunosuppressant, acute rejection episodes, and serum creatinine at 1 year were significantly associated with regraft survival. Cox regression demonstrated the dominant effect of acute rejection episodes, primary maintenance immunosuppressant, serum creatinine at 1 year, and time to first graft loss as predictor of second graft outcome. However, when long-term survival of second graft was examined on the basis of Kaplan-Meier estimates, HLA mismatch was found to be significant. The second graft had more benefits of improved pre-transplant screening and post-transplant management, and its survival rate was satisfactory and similar to that of primary one. Immunologic factors such as acute rejection and primary immunosuppressant are the main determinants of long-term renal transplantation outcome.
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Affiliation(s)
- Dong Wang
- Organ Transplant Institute, Fuzhou general Hospital, Fuzhou 350025, China
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Detecting and monitoring human leukocyte antigen-specific antibodies. Hum Immunol 2008; 69:591-604. [PMID: 18692106 DOI: 10.1016/j.humimm.2008.06.013] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2008] [Revised: 06/16/2008] [Accepted: 06/17/2008] [Indexed: 01/26/2023]
Abstract
Renewed awareness of the relevance of HLA-specific antibodies to transplantation and the development of protocols to reduce or eliminate sensitization have made monitoring of antibodies and accurate interpretation of test results increasingly important. Here we review the various tests available and provide guidelines for the development of monitoring protocols.
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Abstract
New technologies have resulted in the ability to identify the presence of IgG human leukocyte antigen (HLA) or non-HLA antibodies in the sera of potential solid organ transplant recipients. Knowledge of the presence of these antibodies, their antigen specificities, and strength (titer) is crucial to understanding a patient's state of immunologic sensitization and reactivity. Finally, these data, when correlated with sensitive crossmatch results, allow clinicians to make more knowledgeable clinical decisions when paring donors and recipients for transplant.
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Affiliation(s)
- Ronald H Kerman
- The University of Texas Medical School, Houston, TX 77030, USA.
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Won DI, Jeong HD, Kim YL, Suh JS. Simultaneous detection of antibody binding and cytotoxicity in flow cytometry crossmatch for renal transplantation. CYTOMETRY PART B-CLINICAL CYTOMETRY 2006; 70:82-90. [PMID: 16470535 DOI: 10.1002/cyto.b.20089] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND The anti-HLA antibody can be detected using either a complement-dependent lymphocytotoxicity (CDC) assay or a flow cytometry crossmatch (FCXM) in renal transplantation. Discordant results are often obtained because the two methods detect different reaction phases between the donor lymphocytes and the recipient sera. This study was intended to confirm that antibody binding and cytotoxicity to the lymphocytes can be detected simultaneously in a single FCXM assay, cytotoxic FCXM. METHODS In the cytotoxic FCXM, the antibody binding to the lymphocytes was measured using anti-IgG-FITC, and the cytotoxicity using 7-aminoactinomycin D (7-AAD) after adding complement. For an evaluation of two test parameters, the cytotoxicity test moiety (dead-cell percentage) was compared with the anti-human globulin (AHG)-CDC, and the antibody-binding test moiety (sample/control fluorescence ratio) with the conventional FCXM in 77 positive and 30 negative crossmatches. RESULTS In the cytotoxic FCXM, both antibody binding and cytotoxicity could be assessed in a single anti-IgG-FITC/7-AAD plot. Regarding the correlation between the presence of HLA antibodies and the test result, the cytotoxicity parameter (r = 0.55) appeared to be more suitable than that of the AHG-CDC (r = 0.50) but the antibody-binding parameter (r = 0.83) was worse than that of the conventional FCXM (r = 0.93). The sensitivity of both parameters of the cytotoxic FCXM was not significantly different from each conventional counterpart (P = 0.33 and P = 0.22, respectively). CONCLUSIONS The simultaneous detection of Ab binding and cytotoxicity was possible by the cytotoxic FCXM with the test efficiencies similar to the conventional counterparts. If this new assay is improved through the further studies to optimize the critical assay variables, this may be used as an alternative to the conventional assays to acquire more information on the characteristics of the recipient's HLA alloantibodies.
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Affiliation(s)
- Dong Il Won
- Department of Laboratory Medicine, Kyungpook National University Hospital, Daegu, Korea.
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Clinical significance of HLA antigens and non-HLA antigens in solid organ transplantation. Curr Opin Organ Transplant 2006. [DOI: 10.1097/01.mot.0000236707.06200.17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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McLaughlin K, Manns B, Nickerson P. The Routine Use of High-Resolution Immunological Screening of Recipients of Primary Deceased Donor Kidney Allografts Is Cost-Effective. Transplantation 2006; 81:1278-84. [PMID: 16699455 DOI: 10.1097/01.tp.0000205797.05544.e5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The economic and health benefits of kidney transplantation are dependent on the length of allograft survival. High-resolution immunological screening can identify recipients at increased risk of early graft loss caused by acute rejection, but the use of these tests increases screening costs before transplantation. The objective of this study was to evaluate the cost-effectiveness of routine use of high-resolution flow-cytometry cross-matching and solid-phase screening for all recipients of primary deceased donor kidney transplants. METHODS A Markov model was constructed to evaluate costs and effects of two different clinical strategies on a simulated cohort of 1,000 transplant recipients: serological screening (SS) only and flow screening (FS) only. Outcomes measures were total cost of patient care over 25 years, life expectancy, quality-adjusted life expectancy, and transplant life expectancy. RESULTS In the base-case analysis, FS was associated with an average gain of 0.08 life years, 0.25 transplant life years, and 0.08 quality-adjusted life years per patient. SS was associated with a higher cost of CND$6,397 per patient, mostly because of increased use of dialysis in patients who suffered early graft loss under the SS strategy. The results were robust to uncertainty in the majority of variables, and a strategy using FS was cost-effective except under the unlikely scenario where the false-negative rate for SS was <or=2% or the early graft loss rate for flow-positive recipients was <or=7% (compared with 5% for flow-negative recipients). CONCLUSIONS Routine use of FS in recipients of first-deceased donor kidney transplants is cost-effective.
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Affiliation(s)
- Kevin McLaughlin
- Division of Nephrology, University of Calgary, Calgary, Alberta, Canada.
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Kimball P, Wagner B. Elevated B-cell autoantibodies among HIV+ transplant candidates: crossmatch implications. Transplant Proc 2006; 37:4191-3. [PMID: 16387075 DOI: 10.1016/j.transproceed.2005.10.051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2005] [Indexed: 11/15/2022]
Abstract
We report our experience in assessing autoantibodies among HIV+ patients considered for renal transplantation. Autoantibodies against autologous T and B cells were determined by complement-dependent cytotoxicity autocrossmatching (CDC) or flow cytometric autocrossmatching (FCXM) for 28 HIV+ and 72 HIV- men. T-cell CDC was negative among HIV+ and HIV- individuals (0%). In contrast, B-cell CDC was higher among HIV+ than HIV- patients (71% vs 4%, P = .001). However, HIV+ patients also showed unusual sensitivity to complement that potentially invalidated the B-cell CDC. Complement sensitivity was higher among those with positive versus negative HIV RNA (71% vs 25%, P < .01). Alternate use of FCXM showed equivalent T-cell FCXM between HIV+ versus HIV- individuals (5% vs 1%, P = NS). However, B-cell FCXM was more prevalent among HIV+ than HIV- patients (45% vs 2%, P < .01). B-cell FCXM was higher among patients with positive than negative HIV RNA (57% vs 25%, P < .05). Simulated allocrossmatching against unrelated DR-matched donors showed that two out of four HIV+ patients with positive FCXM had positive allocrossmatches that were eliminated when allocrossmatching was repeated using autoabsorbed serum. We conclude that HIV+ patients are more likely to produce B-cell autoantibodies than HIV- individuals, which, if not realized, could cause false-positive allocrossmatches and inappropriate transplant denial.
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Affiliation(s)
- P Kimball
- Department of Transplant Surgery, Medical College of Virginia Hospitals, Richmond, Virginia 23298, USA.
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Abstract
The recent availability of pigs homozygous for alpha1,3-galactosyltransferase gene knockout, and improved immunosuppressive regimens that prevent an elicited antibody response, are expected to contribute to significantly increased survival of pig organs transplanted into primates, bringing clinical trials of xenotransplantation closer. Patients highly sensitized to human leukocyte antigens, who may be precluded from obtaining a human donor organ, would be one group that might benefit from xenotransplantation. However, there have been few studies on whether there is cross-reactivity of anti-human leukocyte antigen antibodies with pig antigens. What data there are suggest that such cross-reactivity exists and that this may be detrimental to the outcome after transplantation of a pig organ. Neither is it known whether sensitization after a pig xenograft would preclude subsequent allotransplantation, although the data available suggest that this will not be the case. Further investigation on allo- and xenoantibody cross-reactivity is required.
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Affiliation(s)
- D K C Cooper
- Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
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Gebel HM, Bray RA, Nickerson P. Pre-transplant assessment of donor-reactive, HLA-specific antibodies in renal transplantation: contraindication vs. risk. Am J Transplant 2003; 3:1488-500. [PMID: 14629279 DOI: 10.1046/j.1600-6135.2003.00273.x] [Citation(s) in RCA: 270] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Howard M Gebel
- Department of Pathology, Emory University Hospital, Atlanta, GA, USA.
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Coupel S, Giral-Classe M, Karam G, Morcet JF, Dantal J, Cantarovich D, Blancho G, Bignon JD, Daguin P, Soulillou JP, Hourmant M. Ten-year survival of second kidney transplants: impact of immunologic factors and renal function at 12 months. Kidney Int 2003; 64:674-80. [PMID: 12846765 DOI: 10.1046/j.1523-1755.2003.00104.x] [Citation(s) in RCA: 78] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND The aim of the present study was to assess long-term survival of cadaveric second kidney allografts performed in our center and to determine risk factors predictive of long-term graft outcome. METHODS Of 1704 kidney transplantations performed between January 1985 and March 1998, 233 were second grafts. The majority of the recipients were sensitized. All patients were treated with the same quadruple immunosuppressive regimen. RESULTS Kaplan-Meier analysis documented graft survival of 89% at 1 year, 76% at 5 years, and 53% at 10 years. Graft survival was similar for second and primary kidney transplants performed during the same period of time. When long-term second graft survival was examined, only two risk factors were found to be significant: (1) the degree of human leukocyte antigen (HLA) DR mismatch (MM) and (2) the number of acute rejection episodes. Multivariate analysis of several pre- and posttransplant variables also confirmed the importance of HLA MM (DR> A), but also, identified serum creatinine at 12 months as the most significant predictor of graft survival. In addition, the Cox proportional hazards model revealed that only the year of transplantation had an independent significant effect on acute rejection occurrence (RR = 0.591, 95%CI 0.437 to 0.801, P < 0.0007). Indeed, the incidence of acute rejection was found to decrease over time (44% of patients experienced at least one episode of acute rejection before 1990 vs. 17% after 1990). CONCLUSION Finally, second graft long-term outcome shows an improved evolution according to the time period resulting from a strong decrease in acute rejection incidence and the impact of creatinine at 12 months.
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Affiliation(s)
- Stéphanie Coupel
- Institut de Transplantation et de Recherche en Transplantation and INSERM U437, Immunointervention en Allo et Xénotransplantations, Nantes, France.
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Bryan CF, Martinez J, Muruve N, Nelson PW, Pierce GE, Ross G, Shield CF, Warady BA, Aeder MI, Harrell KM, Helling TS, Luger AM. IgM antibodies identified by a DTT-ameliorated positive crossmatch do not influence renal graft outcome but the strength of the IgM lymphocytotoxicity is associated with DR phenotype. Clin Transplant 2002; 15 Suppl 6:28-35. [PMID: 11903383 DOI: 10.1034/j.1399-0012.2001.00005.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
A positive crossmatch that is rendered negative by treating the serum with the IgM-reducing agent dithiothreitol (DTT) is generally reported not to influence short-term renal graft outcome. Its effect on long-term (> or = 3 years) cadaveric and live-donor transplant function, however, is less clear. We evaluated the effect of IgM antibodies in a DTT-ameliorated positive crossmatch (DTT-APXM) on long-term renal graft outcome in 1,290 consecutive cadaveric renal transplants (8-year survival) and 384 live-donor renal transplants (7-year survival) from patients transplanted between 1990 and 1999. The data show that 1- and 8-year graft survival for cadaveric renal transplants in patients with IgM antibodies (n=72) (DWFG censored = 91% and 65%; DWFG not censored = 90% and 60%) was not significantly different from the group without IgM antibodies (n = 1,218) (DWFG censored = 92% and 71%; DWFG not censored = 87% and 55%) (log-rank = 0.25 for DWFG censored, log-rank = 0.92 for DWFG not censored). The one- and seven-year graft survival for live-donor renal transplants in patients with IgM antibodies seen in a DTT-APXM (n = 22) (DWFG censored = 95% and 83%; DWFG not censored = 95% and 66%) was not significantly different from the group without IgM antibodies (n = 362) (DWFG censored = 94% and 81%; DWFG not censored = 92% and 73%) (log-rank = 0.61 for DWFG censored, log-rank = 0.89 for DWFG not censored). DR phenotype was found to be associated with the strong (>40% cell death) IgM reactivity in both black and white patients. In white patients, DR2 was more frequently seen with a strong IgM crossmatch (48.2%) than in molecularly typed controls (28.5%) (P < 0.03) and concomitant with that DR increase, DR4 was decreased in white patients (6.8%) compared with controls (25.5%) (P < 0.02). In black patients with strong IgM reactivity, DR6 was increased in patients (46.1%) compared with controls (20.5%) (P = 0.07) and concomitant with that DR6 increase, DR5 was decreased in frequency in black patients (7.6%) compared with controls (41%) (P < 0.03). These data show that long-term graft survival in renal transplantation is not negatively influenced by the presence of donor-reactive lymphocytotoxic antibodies in the crossmatch ameliorated by serum DTT treatment. They also suggest that the strength of the IgM antibody response is regulated in part by certain gene (s) of the DR region.
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Affiliation(s)
- C F Bryan
- Midwest Transplant Network, Westwood, Kansas 66205, USA
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Baron C, Pastural M, Lang P, Bentabet R, el-Kassar N, Seror T, Dahmane D, Desvaux D, Chopin D, Fruchaud G, Remy P, Grimbert P, Lepage E, Bierling P. Long-term kidney graft survival across a positive historic but negative current sensitized cross-match. Transplantation 2002; 73:232-6. [PMID: 11821736 DOI: 10.1097/00007890-200201270-00014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND The sensitive cross-match (XM) techniques that have been introduced for clinical transplantation can detect anti-donor immune reactivity despite a negative standard National Institute of Health (NIH) cross-match. One of them uses anti-kappa human light chain globulins (AHG). But there is some discussion about the clinical consequences of a positive AHG-XM in the historical sera that became negative in the sera collected just before the transplantation (pretransplant sera). This study was intended to assess the risk of kidney graft failure associated with a positive historic but negative pretransplant AHG-XM in allosensitized patients having a negative historic NIH-XM. METHODS This retrospective study includes 90 consecutive renal transplants in immunized patients performed at one center between 1985 and 1991. All of the patients had negative historical and pretransplant standard NIH lymphocytotoxic cross-matches and received the same immunosuppressive regimen. The AHG-XMs were done retrospectively using peak historic and sera collected on the day of the transplantation. RESULTS The AHG cross-match (AHG-XM) was positive in 17 patients, although the standard NIH cross-match was negative. Fourteen of them had a positive historical but negative pretransplant AHG-XM. The actuarial graft survival in this group of 14 patients was 100% at 1 year and 78% at 9 years compared with 90 and 67%, respectively, in patients with negative historical AHG-XM. In addition, the number of rejection episodes per patient as well as renal function at 1, 2, and 5 years were similar in the two groups. IgG anti-donor HLA class I accounted for the XM positivity in 12 of the 14 patients; most rapidly lost all antibody reactivity by NIH technique in an average time of 8 months before the transplantation. In conclusion, this study suggests that transplant patients having a negative historic NIH-XM but a positive historic AHG-XM may not be at high risk of graft failure especially if there is a well-documented sera history showing a marked decrease in PRA level before transplantation and a negative pretransplant AHG-XM.
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Affiliation(s)
- Christophe Baron
- Transplantation Biology Research Center, Massachusetts General Hospital, Boston, USA
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Vaidya S, Cooper TY, Avandsalehi J, Barnes T, Brooks K, Hymel P, Noor M, Sellers R, Thomas A, Stewart D, Daller J, Fish JC, Gugliuzza KK, Bray RA. Improved flow cytometric detection of HLA alloantibodies using pronase: potential implications in renal transplantation. Transplantation 2001; 71:422-8. [PMID: 11233905 DOI: 10.1097/00007890-200102150-00015] [Citation(s) in RCA: 70] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Flow cytomeric crossmatch (FCXM) has grown in popularity and has become the "standard of practice" in many programs. Although FCXM is the most sensitive method for detecting alloantibody, the B cell FCXM has been problematic. Difficulties with the B cell FCXMs have been centered around high nonspecific fluorescence background owing to Fc-receptors present on the B cells and autoantibodies. To improve the specificity and sensitivity of the B cell FCXM, we utilized the proteolytic enzyme pronase to remove Fc receptors from lymphocytes before their use in FCXM. METHODS Lymphocytes isolated from peripheral blood, spleen, or lymph nodes were treated with pronase and then used in a three-color FCXM. A total of 167 T- and B cell FCXMs using pronase-treated and untreated cells were performed. Testing used serial dilutions of HLA allosera (22 class I and 6 class II), with the titer of each antibody at one dilution past the titer at which the complement-mediated cytotoxicity anti-human globulin crossmatch became negative. RESULTS After pronase treatment, the actual channel values of the negative control in both T cell and B cell FCXMs declined from 78+/-10 to 57+/-4 (P<0.05) and 107+/-11 to 49+/-3 (P<0.00001), respectively. Pronase treatment resulted in improved sensitivity of the T and B cell FCXM in detecting class I antibody by 20% and 80%, respectively. In no instance was a false-positive reaction observed. In this study, pronase treatment improved the specificity of B cell FCXM for detecting class II antibodies from 75% to 100% (P=0.03). In no instance was a false-negative reaction recorded. Lastly, on the basis of these observations we re-evaluated three primary transplant recipients who lost their allografts because of accelerated rejection. One of the patients was transplanted across negative T and B cell FCXM, whereas the other two patients were transplanted across a positive T cell, but negative B cell, FCXM. After pronase treatment, T and B cell FCXMs of each patient became strongly positive, and donor-specific anti-HLA class I antibody was identi. fied in each case. CONCLUSION Utilization of pronase-treated lymphocytes improves both the sensitivity and specificity of the FCXM.
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Affiliation(s)
- S Vaidya
- Department of Pathology, University of Texas Medical Branch, Galveston 77555-0178, USA
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Zachary AA, Ratner LE, Leffell MS. Low levels of HLA-specific antibody: relevance, detection, and treatment. Transplant Proc 2001; 33:469-70. [PMID: 11266912 DOI: 10.1016/s0041-1345(00)02096-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- A A Zachary
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Barama A, Oza U, Panek R, Belitsky P, MacDonald AS, Lawen J, McAlister V, Kiberd B. Effect of recipient sensitization (peak PRA) on graft outcome in haploidentical living related kidney transplants. Clin Transplant 2000; 14:212-7. [PMID: 10831079 DOI: 10.1034/j.1399-0012.2000.140306.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To evaluate the influence of pre-transplant recipient sensitization on the outcome of 1-haploidentical live related donor (LRD) kidney transplants. METHOD We reviewed 141 consecutive cyclosporine-treated adult haploidentical first transplants for which panel reactive antibody (PRA) levels were available. Patients were divided into three groups according to their peak PRA levels: group I, PRA = 0 (n = 97); group II, PRA = 1-50% (n = 24); and group III, PRA = 51-100% (n = 20). RESULTS Differences in PRA were associated with significant differences in short- and longer-term graft survival, unrelated to patient survival. Graft survival at 1, 3, and 5 yr was only 74, 40, and 27% in group III, compared to 92, 87, and 52% in group II, and 96, 91, and 85% in group I (p < 0.001). Increasing PRA was associated with shorter time-to-graft failure. In group III, 20% lost their transplant from acute rejection in the first 6 months, versus 4% in group II and 3% in group I (p < 0.01). Graft survival in group II diverged from that of group I only after 3 yr, due to an increase in loss from chronic rejection. Hospitalization was longer in group III, in association with a significantly higher incidence of acute rejection during the first 3 months after transplantation (p < 0.02). Serum creatinine was higher in sensitized than nonsensitized patients at all time points. CONCLUSIONS Sensitization has a significant negative impact on the outcome of haploidentical LRD kidney transplants. Sensitized potential recipients and their potential donors should be aware of this in arriving at informed decision-making for transplantation. These patients may benefit from more sensitive cross-match testing, more intense or more novel immunosuppression, or immunomodulation to modify their immune responsiveness.
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Affiliation(s)
- A Barama
- Department of Surgery, FMC, Calgary, Alberta, Canada
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Kerman RH, Susskind B, Buyse I, Pryzbylowski P, Ruth J, Warnell S, Gruber SA, Katz S, Van Buren CT, Kahan BD. Flow cytometry-detected IgG is not a contraindication to renal transplantation: IgM may be beneficial to outcome. Transplantation 1999; 68:1855-8. [PMID: 10628764 DOI: 10.1097/00007890-199912270-00007] [Citation(s) in RCA: 77] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND At our transplant center, primary recipients of either a haplo-identical (haplo-ID) living related (LRD) or a cadaveric (CAD) donor renal allograft are transplanted after a negative donor-specific IgG anti-human globulin (AHG) cross-match (XM). Testing included the historically highest panel-reactive antibody and the immediate (0-7 days) pretransplant sera. A positive donor specific IgM-AHG XM has not been a contraindication to transplant. Reports suggest that donor-specific flow cytometry cross-matches (FCXM) may be more clinically informative than the AHG-XM. METHODS We therefore evaluated the impact of a positive FCXM (IgG or IgM) on the rejection frequency (0-12 months after transplant) and 1-year graft survival for cyclosporine-prednisone-treated primary (haplo-ID and CAD) renal allograft recipients. All transplants were performed after a negative donor-specific IgG AHG-XM regardless of the IgM-AHG XM status. RESULTS Rejection frequencies (26% vs. 31%, P = NS) and 1-year graft survivals (92% vs. 89%, P = NS) were comparable for haplo-ID LRD FCXM-negative and IgG-FCXM-positive recipients. However, IgM-FCXM-positive LRD recipients experienced significantly fewer rejections (13% vs. 26% P<0.02) and an improved 1-year graft survival (100% vs. 92%, P<0.02) than FCXM-negative LRD recipients. Similar results were observed for primary CAD recipients. Rejection frequencies (40% vs. 44%, P = NS) and 1-year graft survivals (83% vs. 81%, P = NS) were comparable for primary CAD FCXM-negative and IgG-FCXM-positive recipients. Again, IgM-FCXM-positive primary CAD recipients experienced significantly fewer rejections (22% vs. 40%, P<0.02) and improved 1-year graft survivals (89% vs. 83%, P<0.05) than FCXM-negative recipients. CONCLUSION These data suggest that, after a negative donor-specific IgG-AHG XM, an IgG-positive FCXM is not a contraindication to transplantation. The presence of IgM may be beneficial in reducing the occurrence of rejection episodes and improving graft survivals.
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Affiliation(s)
- R H Kerman
- Department of Surgery, University of Texas Medical School, Houston 77030, USA
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Przybylowski P, Balogna M, Radovancevic B, Frazier OH, Susskind B, Van Buren C, Katz S, Kahan BD, Kerman R. The role of flow cytometry-detected IgG and IgM anti-donor antibodies in cardiac allograft recipients. Transplantation 1999; 67:258-62. [PMID: 10075590 DOI: 10.1097/00007890-199901270-00012] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND At our transplant center, cardiac allograft recipients undergo transplantation following a negative IgG anti-human globulin (AHG) crossmatch (XM). Flow cytometry crossmatching (FCXM) is a more sensitive XM procedure than the AHG XM procedure, yet there is limited information regarding the clinical relevance of FCXM to cardiac allograft outcome. METHODS FCXM was performed retrospectively using the pretransplant sera from 140 recipients of primary cardiac allografts who underwent transplantation after AHG-IgG-NEG XM. The FCXM results were correlated to posttransplant rejection and patient survival. RESULTS All of the patients were auto-XM-NEG. Twenty-two of 140 patients (16%) displayed IgG(+) FCXM and had a significantly poorer 1-year survival rate than did 57 of the FCXM-NEG recipients (68% vs. 86%, P<0.02). Moreover, 50% of the IgG(+) FCXM recipients experienced early rejections (< or =14 days postoperatively) compared with only 16% for the FCXM-NEG recipients (P<0.01). The survival rate of 92% for IgM(+) FCXM recipients (n=37) was significantly improved compared with the 86% survival rate for FCXM-NEG control recipients (P<0.05), suggesting a protective role for IgM. Consistent with this interpretation is that the 1-year survival rate of 79% for the IgG, IgM FCXM(+) recipients (n=24) was significantly better than the 68% survival rate for the IgG(+) FCXM recipients (P<0.02). CONCLUSIONS These data suggest that IgG(+) FCXM identifies a subset of AHG-IgG-NEG XM cardiac allograft recipients who are at risk for early rejections and poor survival. In contrast, the presence of IgM may be beneficial to survival.
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Affiliation(s)
- P Przybylowski
- Department of Surgery, The University of Texas Medical School, and The Texas Heart Institute, Houston 77030, USA
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Kerman RH, Susskind B, Ruth J, Katz S, Van Buren CT, Kahan BD. Can an immunologically, nonreactive potential allograft recipient undergo transplantation without a donor-specific crossmatch? Transplantation 1998; 66:1833-4. [PMID: 9884284 DOI: 10.1097/00007890-199812270-00044] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Performance of the pretransplant crossmatch requires 4 or more hours . Delays in the crossmatch might alter operating room availability and thereby increase donor organ cold ischemia time that might then result in increased risk of delayed graft function. To avoid these problems, recipients could be identified who would be expected to display negative donor crossmatches and who could be transplanted with a concurrent or retrospective rather than a pretransplant crossmatch. We, therefore, evaluated the percent reactive antibodies and donor IgG-antihuman globulin (AHG) crossmatch results of 1165 sera from 220 potential allograft recipients. Twenty-five (11%) of 220 recipients consistently displayed a 0% PRA and, with only one exception, their sera (n= 156) tested IgG-AHG crossmatch-negative against potential cadaveric donors (a 0.6% IgG-AHG positive crossmatch risk). These data suggest that the timing of the pretransplant serum crossmatch could be altered for a highly selected group of immunologically nonreactive recipients.
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Affiliation(s)
- R H Kerman
- Department of Surgery, University of Texas Medical School, Houston 77030, USA
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Susskind B, Kerman RH, Nelson R, Gregory J, La T, Bayat A, Dang M, Van Buren C, Katz S, Kahan BD. Comparison between enzyme-linked immunosorbent assay and cytotoxic cross-match procedures for detecting IgG anti-donor antibodies. Transplantation 1998; 66:1823-6. [PMID: 9884282 DOI: 10.1097/00007890-199812270-00042] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Disadvantages inherent to complement-dependent cytotoxicity cross-match (CDC XM) methods are the requirements for complement and viable target cells, detection of antibodies (Abs) against non-HLA antigens, and subjective scoring. Cross-Stat (SangStat Medical Corp., Menlo Park, CA), a recently developed enzyme-linked immunosorbent assay XM procedure for the detection of IgG anti-donor HLA Abs, is theoretically devoid of these flaws. METHODS We compared results of Cross-Stat and our standard anti-human globulin (AHG)-enhanced CDC XM procedure on 524 sera from 230 transplant candidates, which were evaluated against 51 cadaveric donors. RESULTS There was a significant correlation between AHG-CDC IgG XM and Cross-Stat results (P<0.001). For false negative sera, repeat AHG-CDC IgG XMs were still positive after platelet absorption, indicating that the Abs present were either non-HLA Abs or anti-HLA class II. Flow cytometry testing of false positive sera usually (42/62) substantiated Cross-Stat results, indicating that the discrepancy with AHG-CDC IgG XM is caused by greater sensitivity of Cross-Stat. Relative to the AHG-CDC XM, the sensitivity of Cross-Stat was 100%, the specificity was 93%, the positive predictive value was 73%, and the negative predictive value was 100%. A technical shortcoming of the Cross-Stat assay is that the frequency of indeterminate samples in the assays was 15%. Among 49 Cross-Stat negative vs. 13 Cross-Stat positive primary cadaveric renal allograft recipients (all AHG-CDC IgG-XM negative), there was no statistical difference in overall graft survival. CONCLUSION Given the important theoretical advantages of enzyme-linked immunosorbent assay-based XM methods over the CDC XM, however, further testing of the clinical relevance of the Cross-Stat is warranted.
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Affiliation(s)
- B Susskind
- Division of Immunology and Organ Transplantation, University of Texas Health Science Center, Houston, USA
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Bathgate AJ, McColl M, Garden OJ, Forsythe JL, Madhavan KK, Hayes PC. The effect of a positive T-lymphocytotoxic crossmatch on hepatic allograft survival and rejection. LIVER TRANSPLANTATION AND SURGERY : OFFICIAL PUBLICATION OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES AND THE INTERNATIONAL LIVER TRANSPLANTATION SOCIETY 1998; 4:280-4. [PMID: 9649641 DOI: 10.1002/lt.500040411] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The influence of crossmatching in liver transplantation is still controversial, and at present, our unit does not alter management according to the result of standard lymphocytotoxicity testing. This study retrospectively assessed outcome of grafts transplanted in the presence of preformed antidonor cytotoxic antibody. One hundred twelve patients undergoing their first orthotopic liver transplantation had results available (mean follow-up: 18 months). Twelve patients had a positive crossmatch and 100 negative. The 1-year graft survival was 58% in the positive crossmatch group, compared with 81% in the negative crossmatch group (P = .02). The 1-year patient survival was 83% in the positive crossmatch group compared with 90% in the negative group (P = .41). Acute cellular rejection occurred in 6 of 7 (86%) grafts surviving more than 7 days in the positive crossmatch group compared with 46 of 88 (52%) grafts in the negative group (P = .09). However, episodes of further acute cellular rejection requiring treatment occurred in 4 of the 6 grafts in the positive crossmatch group but in only 4 of the 46 grafts with a negative crossmatch (P = .0006). The authors conclude that evidence exists in our population that preformed antidonor antibodies adversely affect the outcome of hepatic allografts but not patient survival.
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Affiliation(s)
- A J Bathgate
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh, Scotland
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Bishara A, Sherman L, Brautbar C, Claas F, Friedlander M, Rubinger D, Berlatzky Y, Papo O, Eid A. Pretransplant crossmatching: an individualized process. Transplant Proc 1997; 29:2708-10. [PMID: 9290799 DOI: 10.1016/s0041-1345(97)00565-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- A Bishara
- Tissue Typing Unit, Hadassah Medical Center, Jerusalem, Israel
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Kerman RH, Susskind B, Kerman DH, Lam M, Gerolami K, Williams J, Kalish R, Campbell M, Katz SM, Van Buren CT, Kahan BD. Anti-HLA antibodies detected in posttransplant renal allograft recipient sera correlate with chronic rejection. Transplant Proc 1997; 29:1515-6. [PMID: 9123406 DOI: 10.1016/s0041-1345(96)00656-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- R H Kerman
- Department of Surgery, University of Texas Medical School, Houston 77030, USA
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Bartholomew A, Latinne D, Sachs D, Arn JS, Gianello P, Bruyere ML, Sokal G, Squifflet J, Alexandre G, Comerford C, Saidman S, Cosimi A. Utility of xenografts: Lack of correlation between PRA and natural antibodies to swine. Xenotransplantation 1997. [DOI: 10.1111/j.1399-3089.1997.tb00162.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Christiaans MH, Overhof R, ten Haaft A, Nieman F, van Hooff JP, van den Berg-Loonen EM. No advantage of flow cytometry crossmatch over complement-dependent cytotoxicity in immunologically well-documented renal allograft recipients. Transplantation 1996; 62:1341-7. [PMID: 8932282 DOI: 10.1097/00007890-199611150-00028] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The effect of flow cytometry crossmatches on clinical outcome was studied retrospectively in two groups of immunologically well-documented patients who had received transplants with a negative complement-dependent cytotoxicity crossmatch. The first group consisted of 114 consecutive renal allograft recipients, and the second group consisted of 76 immunologically at-risk recipients. Flow cytometry crossmatches were performed with current and historic sera. In group 1, positive flow cytometry (FC) crossmatches were shown in 15/114 (13%) recipients. Rejection occurred in 8/15 (53%) FC-positive versus 41/99 (41%) FC-negative recipients. The 1-year graft survival rate was 80% for FC-positive patients and 87% for FC-negative patients. Sixty-seven patients were nonsensitized patients; 4 of them had a positive FC crossmatch but no rejection episodes, graft loss, or patient loss. Of 47 retransplanted and/or sensitized recipients, 11 had a positive FC crossmatch. Rejection treatment was needed in 8/11 (73%) FC-positive patients compared with 19/36 (53%) FC-negative patients. Their 1-year graft survival rates were 73% and 81%. None of these differences reached statistical significance. Group 2 consisted of 76 at-risk recipients; 37 were retransplant patients and 39 were sensitized first-transplant patients. Twenty-one (28%) patients showed a positive FC crossmatch. Rejection episodes did not differ between the FC-positive (48%) and FC-negative patients (46%). There was no difference in 1-year graft survival rate (76% vs. 80%) or in 1-year patient survival rate (100% vs. 95%). We conclude that FC crossmatches in our patient group are not superior to the classical complement-dependent cytotoxicity crossmatches with regard to clinical outcome. On the contrary, transplantation with a mandatory negative FC crossmatch would have excluded 28% of the recipients from transplantation, who in fact are doing well.
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Affiliation(s)
- M H Christiaans
- Department of Internal Medicine, University Hospital Maastricht, The Netherlands
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Nanni-Costa A, Scolari MP, Iannelli S, Vangelista A, Buscaroli A, Liviano D'Arcangelo G, Buttazzi R, de Sanctis LB, Todeschini P, Stefoni S, Bonomini V. ELISA anti-HLA antibody screening identifies non-complement-fixing antibodies responsible for acute graft rejection. A case report. EUROPEAN JOURNAL OF IMMUNOGENETICS : OFFICIAL JOURNAL OF THE BRITISH SOCIETY FOR HISTOCOMPATIBILITY AND IMMUNOGENETICS 1996; 23:383-7. [PMID: 8909945 DOI: 10.1111/j.1744-313x.1996.tb00011.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
We report on a kidney transplant recipient experiencing an unexpected early acute vascular graft rejection. Retrospective analysis of patient serum samples, utilizing a new ELISA HLA screening technique, revealed that the rejection crisis and the subsequent graft loss were due to a pretransplant donor-specific pre-sensitization caused by a non-complement-fixing antibody of IgG2 class. The case illustrates the clinical significance of non-complement-fixing anti-HLA antibodies. In addition it is shown that ELISA methods are suitable for detecting potentially harmful donor pre-sensitization in waiting-list patients not detectable by standard lymphocytotoxicity techniques. Hence ELISA could be an alternative to flow cytometry for this purpose. It is concluded that screening and cross-matching techniques which detect non-complement-fixing anti-HLA antibodies could improve graft outcome, and should form part of the immunological monitoring of kidney transplant waiting-list patients.
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Affiliation(s)
- A Nanni-Costa
- Institute of Nephrology, St. Orsola University Hospital, Italy
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Doyle HR, Marino IR, Morelli F, Doria C, Aldrighetti L, McMichael J, Martell J, Gayowski T, Starzl TE. Assessing risk in liver transplantation. Special reference to the significance of a positive cytotoxic crossmatch. Ann Surg 1996; 224:168-77. [PMID: 8757380 PMCID: PMC1235338 DOI: 10.1097/00000658-199608000-00009] [Citation(s) in RCA: 67] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVE The authors determined the impact of a positive cytotoxic crossmatch on the outcome of liver transplantation. SUMMARY BACKGROUND DATA Liver allografts rarely undergo hyperacute rejection, but transplants performed across a positive cytotoxic crossmatch tend to follow a different clinical course, with higher intraoperative blood use, postoperative graft dysfunction, and, in some cases, graft loss. How this affects overall graft survival has not been determined. METHODS The authors provide a retrospective analysis of 1520 liver transplants performed between November 1989 and December 1993, with a minimum follow-up of 1 year. All cases had a cytotoxic crossmatch using serum pretreated with dithiothreitol. RESULTS There were 1390 negative crossmatch and 130 positive crossmatch cases. There was no difference in overall graft survival, although early survival rates were lower in the positive crossmatch group, with the maximum difference at 6 months: 0.76 (95% confidence interval, 0.74-0.78) for a negative crossmatch versus 0.68 (95% confidence interval, 0.61-0.77) for a positive crossmatch. These differences become negligible by the 2-year mark. Using stepwise logistic regression, the authors identified seven variables independently associated with outcome: 1) donor age, 2) donor gender, 3) prior liver transplant, 4) medical urgency status, 5) ischemia time, 6) indication for transplantation, and 7) primary immunosuppressant. CONCLUSIONS The cytotoxic crossmatch is not statistically associated with overall graft survival after liver transplantation. However, early failure rates are higher in the positive crossmatch cases, a difference that disappears by the second year.
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Affiliation(s)
- H R Doyle
- Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania, USA
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Susskind BM, Kerman RH, Browne BJ, Hartwell BA, Davis BG, Katz SM, Van Buren CT, Kahan BD. The impact of elevated serum IgA and race on primary recipient renal allograft survival. Transplantation 1996; 61:205-11. [PMID: 8600624 DOI: 10.1097/00007890-199601270-00007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
This study correlated overall serum IgA levels in pretransplant (preTx) sera with graft survival. IgA levels, determined by nephelometry, were normally distributed, with a mean level of 255 +/- 139 mg/dl and a median of 234 mg/dl in 631 adult primary kidney allograft recipients and a mean level of 213 +/- 123 mg/dl with a median of 196 mg/dl for 100 retransplant recipients. Improved 3-year survival was associated with a high preTx IgA serum level in primary recipients (Kaplan-Meier analysis, P = 0.01), but not in retransplant patients. After stratifying by race, IgA correlated with graft survival in Caucasian, Hispanic, and "other" (Middle Eastern, Indian subcontinent, and Asian) primary recipients (P < or = 0.04), but not in African Americans. Higher survival rates were not associated with IgA in primary recipients stratified for rejection episodes, blood transfusions, or HLA-DR mismatches. Graft survival was improved in patients with > 2 HLA-AB mismatches and serum IgA above the median. PreTx IgA level and IgA alpha-HLA activity were significantly associated in preTx sera of primary renal allograft recipients (chi 2 = 7.145, P = 0.01), although only 9% (12/133) of sera tested displayed IgA anti-HLA class I reactivity. Thus, enhanced graft survival mediated by elevated serum IgA levels may due in part to competition for allograft HLA class I binding with deleterious Ig subclasses or immune effector cells. Elevated serum IgA may also reflect an altered immunoregulatory state. The results suggest that, depending on the racial group, preTx serum IgA levels are a prognostic indicator of graft survival in primary renal allograft recipients.
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Affiliation(s)
- B M Susskind
- Department of Surgery, University of Texas Medical School-Houston, Houston 77030, USA
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Buelow R, Mercier I, Glanville L, Regan J, Ellingson L, Janda G, Claas F, Colombe B, Gelder F, Grosse-Wilde H. Detection of panel-reactive anti-HLA class I antibodies by enzyme-linked immunosorbent assay or lymphocytotoxicity. Results of a blinded, controlled multicenter study. Hum Immunol 1995; 44:1-11. [PMID: 8522449 DOI: 10.1016/0198-8859(95)00057-b] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
A soluble HLA ELISA for the detection of anti-HLA class I IgG antibodies was developed and compared to complement-dependent microlymphocytotoxicity. ELISA plates were coated with a panel of sHLA class I antigens isolated from the culture supernatants of 46 different EBV-transformed phenotyped B-cell lines. After the incubation of the coated plates with test serum, bound antibodies were detected using a peroxidase-conjugated anti-human IgG antibody. Absorbance was read using an ELISA plate reader and assay results were analyzed by computer. Antibody specificities were determined by Fisher's exact test tail analysis. The reproducibility of ELISA assay results was evaluated in a blinded, controlled multicenter study. A total of 102 serum specimens from patients on waiting lists to receive kidney transplants were tested five times by ELISA in five different laboratories. The correlation coefficients (r) of %PRA values determined by ELISA ranged from 0.89 to 0.96, and the average agreement on qualitative assay results (antibody positive vs antibody negative) was 98%. Endpoint titration of several serum specimens demonstrated equivalent sensitivity of ELISA and microlymphocytotoxicity (using the anti-globulin antibody protocol). Most of the antibody specificities determined by ELISA were in agreement with specificities determined by microlymphocytotoxicity. To evaluate the correlation of ELISA and microlymphocytotoxicity (CDC) assay results the same 102 specimens were tested six times by CDC in five different laboratories. The interlaboratory correlation coefficient (r) of %PRA values determined by microlymphocytotoxicity ranged from 0.57 to 0.94, and the average agreement on qualitative assay results was 85%. A comparison of ELISA with microlymphocytotoxicity was performed using consensus microlymphocytotoxicity results. This showed a high correlation (r = 0.81) of %PRA values determined by ELISA and microlymphocytotoxicity. This demonstrates that the detection of anti-HLA class I antibodies by soluble HLA ELISA is a reliable alternative to microlymphocytotoxicity testing.
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Affiliation(s)
- R Buelow
- SangStat Medical Corporation, Menlo Park, CA 94025, USA
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Abstract
Equitable allocation of human cadaver kidneys is complex and challenging, both from the ethical and scientific points of view. It is based on the principles of distributive justice and medical utility. However, the optimal application of ethical principles will require further resolution of medical issues that currently focus on the number of transplants for a single patient, six antigen matches, lesser degrees of HLA matching, marginal recipients, various positive cross-match situations, and cold ischemia time. New HLA matching techniques and enhanced computer organ allocation systems have the potential to surmount racial differences and increase significantly the number of compatible renal allografts.
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Affiliation(s)
- W E Braun
- Department of Nephrology and Hypertension, Cleveland Clinic Foundation, OH 44195
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Affiliation(s)
- B R Hawkins
- Department of Pathology, Queen Mary Hospital, University of Hong Kong
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