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Virtual crossmatch

Ronald F Parsons, Jayme E Locke, Robert R Redfield, Garrett R Roll, Matthew H Levine
Deceased donor kidney allocation was reorganized in the United States to address several problems, including the highly sensitized patients disadvantaged with large, diverse repertoires of antibodies. Here, five transplant surgeons review their center's experience with the new allocation changes: highlighting areas of accomplishment, opportunities for improvement and, in some cases, stark differences in practice. Across these five centers the highly sensitized patients (CPRA ⩾98%) range from 5.5 to 9.2% of the 12,364 candidates on their collective waitlist...
October 20, 2016: Human Immunology
Vadim Jucaud, Mepur H Ravindranath, Paul I Terasaki
BACKGROUND: Single antigen beads (SAB) are used for monitoring HLA antibodies in pre- and post-transplant patients despite the discrepancy between virtual and actual crossmatch results and transplant outcomes. This discrepancy can be attributed to the presence of conformational variants of HLA-I on SAB, assessment of which would increase the concordance between SAB and flow cytometry crossmatch (FCXM) results, thus enabling improved organ accessibility for the waiting list patients and a better prediction of AMR...
August 5, 2016: Transplantation
Jonathan Visentin, Thomas Bachelet, Cécile Borg, Nicolas Franchini, Thoa Nong, Jar-How Lee, Lionel Couzi, Pierre Merville, Gwendaline Guidicelli, Jean-Luc Taupin
BACKGROUND: In virtual crossmatch (XM) strategies, a correct anticipation of XM results is required for appropriately allocating organs. We reassessed the ability to predict T lymphocyte flow cytometry and complement dependent cytotoxicity XM results with the mean fluorescence intensity (MFI) in Luminex class I single antigen flow beads (SAFB) assay, after correction of complement interference and exclusion of antidenatured HLA antibodies. METHODS: Among 432 XM with T lymphocytes (T-XM), 407 were analyzed after exclusion of antidenatured HLA antibodies...
June 22, 2016: Transplantation
Vinayak S Rohan, David J Taber, Omar Moussa, Nicole A Pilch, Signe Denmark, Holly B Meadows, John W McGillicuddy, Kenneth D Chavin, Prabhakar K Baliga, Charles F Bratton
OBJECIVES: Elevated panel reactive antibody levels have been traditionally associated with increased acute rejection rate and decreased long-term graft survival after kidney transplant. In this study, our objective was to determine patient and allograft outcomes in sensitized kidney transplant recipients with advanced HLA antibody detection and stringent protein sequence epitope analyses. MATERIALS AND METHODS: This was a subanalysis of a prospective, risk-stratified randomized controlled trial that compared interleukin 2 receptor antagonist to rabbit antithymocyte globulin induction in 200 kidney transplant recipients, examining outcomes based on panel reactive antibody levels of < 20% (low) versus ≥ 20% (high, sensitized)...
June 3, 2016: Experimental and Clinical Transplantation
Keylla S U Aita, Semiramis J H Monte, Adalberto S Silva, Mário S C Marroquim, Antônio Gilberto B Coelho, Luiz Claudio D M Sousa
BACKGROUND: The compatibilities between donors and recipients are extremely important for evaluating the immunological risks of transplants. One challenge faced by data analysis tools is the transformation of complex data into simple, intuitive, and important information that can be used to resolve contemporary problems. To address this challenge, we developed the EpViX software to perform epitope reactivity analyses and automated epitope virtual crossmatching. EpViX is a facilitator of medical decision-making regarding the identification of the best donor for a high-immunologic risk recipient...
August 1, 2016: Computers in Biology and Medicine
Anat R Tambur
PURPOSE OF REVIEW: Recent reports on donor-specific antibodies documented an overwhelming frequency of antibodies to one specific locus - human leukocyte antigen DQ (HLA-DQ). This article provides a short summary of clinical observations, a historic perspective to account for the late recognition of the role of HLA-DQ antibodies as well as potential explanations. RECENT FINDINGS: The basic understanding of the complexity of HLA-DQ molecules (antigens and antibodies) existed already 3-4 decades ago...
August 2016: Current Opinion in Organ Transplantation
Paolo Ferrari, Linda Cantwell, Joseph Ta, Claudia Woodroffe, Lloyd DʼOrsogna, Rhonda Holdsworth
BACKGROUND: Participation of compatible pairs (CP) in kidney paired donation (KPD) could be attractive to CPs who have a high degree of HLA mismatch, if the CP recipient will gain a better HLA match. Because KPD programs were not designed to help CP, it is important to define allocation metrics that enable CP to receive a better-matched kidney, without disadvantage to incompatible pairs (ICP). METHODS: Simulations using 46 ICPs and 11 fully HLA-mismatched CPs were undertaken using the Australian KPD matching algorithm...
April 13, 2016: Transplantation
Brian C Eby, Robert R Redfield, Thomas M Ellis, Glen E Leverson, Abby R Schenian, Jon S Odorico
BACKGROUND: Imported pancreata accumulate cold ischemia time (CIT), limiting utilization and worsening outcomes. Flow cytometric crossmatching (FXM) is a standard method to assess recipient and donor compatibility, but can prolong CIT. Single-antigen bead assays allow for detection of recipient donor-specific HLA antibodies, enabling prediction of compatibility through a "virtual crossmatch" (VXM). This study investigates the utility and outcomes of VXM after transplantation of imported pancreata...
May 2016: Transplantation
Howard M Gebel, Bertram L Kasiske, Sally K Gustafson, Joshua Pyke, Eugene Shteyn, Ajay K Israni, Robert A Bray, Jon J Snyder, John J Friedewald, Dorry L Segev
BACKGROUND AND OBJECTIVES: In December of 2014, the Organ Procurement and Transplant Network implemented a new Kidney Allocation System (KAS) for deceased donor transplant, with increased priority for highly sensitized candidates (calculated panel-reactive antibody [cPRA] >99%). We used a modified version of the new KAS to address issues of access and equity for these candidates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a simulation, 10,988 deceased donor kidneys transplanted into waitlisted recipients in 2010 were instead allocated to candidates with cPRA≥80% (n=18,004)...
March 7, 2016: Clinical Journal of the American Society of Nephrology: CJASN
Sandesh Parajuli, Brenda L Muth, Jennifer A Turk, Brad C Astor, Maha Mohammed, Didier A Mandelbrot, Arjang Djamali
BACKGROUND: There is little information on the incidence, risk factors, and outcomes associated with CMV and BK infections in sensitized patients. METHODS: We examined 254 consecutive kidney transplant recipients with positive virtual crossmatch and negative flow crossmatch. RESULTS: A total of 111 patients (43%) developed CMV disease or BK infection or nephropathy (BKVN). Specifically, 78 patients (30.7%) developed BK infection, 19 (7.5%) had BKVN, and 33 (12...
March 2016: Transplantation
J Lugo-Baruqui, G W Burke, G Guerra, P Ruiz, G Ciancio
Reused kidney grafts have been transplanted with successful outcomes, though not widely performed in the Unites States. We present the case of a reused kidney graft with 10-year follow-up. The first donation was from a patient who died from a cerebrovascular accident and whose organs were used for a simultaneous pancreas and kidney transplant. After 5 years, the patient died and kidney was considered for donation and reuse. The patient had a virtual crossmatch with the first donor and a complement-dependent and flow-dependent crossmatch with the second donor...
December 2015: Transplantation Proceedings
Nancy L Reinsmoen, Jignesh Patel, James Mirocha, Chih-hung Lai, Mehrnoush Naim, Geraldine Ong, Qi Wang, Xiaohai Zhang, Frank Liou, Zhe Yu, Jon Kobashigawa
BACKGROUND: The virtual crossmatch relies on the assignment of unacceptable antigens (UAs) to identify compatible donors. The purpose of our study was to identify an algorithm for assignment of UAs such that a negative complement-dependent cytotoxicity (CDC) crossmatch and concomitant negative or weakly positive flow cytometric crossmatch (FXM) are obtained. METHODS: We used 4 antibody methods: (1) Luminex single antigen (LSA), (2) LSA with a 1:8 serum dilution, (3) C1q LSA, and (4) CDC panel...
February 2016: Journal of Heart and Lung Transplantation
G Schlaf, K Stöhr, A Rothhoff, W Altermann
About forty years ago the complement-dependent crossmatch assay (CDC-CM) was developed as standard procedure in order to select recipients without donor-specific antibodies directed against human leukocyte antigens of their given donors since the negative outcome of pretransplant crossmatching represents one of the most important requirements for a successful kidney graft survival. However, as a functional assay the CDC-CM strongly depends on the availability of donors' isolated lymphocytes and in particular on their vitality highly limiting its applicability for recipients treated with special drugs and therapeutic antibodies or suffering from underlying autoimmune diseases...
2015: Case Reports in Transplantation
C P Johnson, J J Schiller, Y R Zhu, S Hariharan, A M Roza, D C Cronin, B D Shames, T M Ellis
Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor-recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long-term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor-specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1 year (AR <1 year) for FCXM+ (n = 54) and FCXM- (n = 454) recipients...
May 2016: American Journal of Transplantation
Fernando Antonio Costa Anunciação, Luiz Claudio Demes da Mata Sousa, Adalberto Socorro da Silva, Mário Sérgio Coelho Marroquim, Antônio Gilberto Borges Coelho, Glauco Henrique Willcox, João Marcelo Medeiros de Andrade, Bruno de Melo Corrêa, Elisabeth Lima Guimarães, Semiramis Jamil Hadad do Monte
One of the challenges facing solid organ transplantation programs globally is the identification of low immunological risk donors for sensitized recipients by HLA allele genotype. Because recognition of donor HLA alleles by host antibodies is at the core of organ rejection, the objective of this work was to develop a new version of the EpHLA software, named EpViX, which uses an HLAMatchmaker algorithm and performs automated epitope virtual crossmatching at the initiation of the organ donation process. EpViX is a free, web-based application developed for use over the internet on a tablet, smartphone or computer...
November 2015: Transplant Immunology
C Süsal, C Seidl, C Schönemann, F M Heinemann, T Kauke, P Gombos, R Kelsch, W Arns, U Bauerfeind, M Hallensleben, I A Hauser, G Einecke, R Blasczyk
One of the major tasks of histocompatibility and immunogenetics laboratories is the pretransplant determination of unacceptable antigen mismatches (UAM) in kidney transplant recipients. In this procedure, human leucocyte antigen (HLA) specificities are defined against which the patient has circulating alloantibodies that are expected to harm the transplanted organ. Using the information on UAM and the potential donor's complete HLA typing, prediction of the crossmatch result, the so called 'virtual crossmatch', is possible...
November 2015: Tissue Antigens
Jonathan Visentin, Gwendaline Guidicelli, Thoa Nong, Jean-François Moreau, Pierre Merville, Lionel Couzi, Jar-How Lee, Jean-Luc Taupin
In addition to antibodies targeting native class I human leukocyte antigens (HLA), the single antigen flow beads assay (SAFB) detects antibodies recognizing denatured forms (anti-dHLA). Acid treated SAFB and the modified SAFB reagent named iBeads are expected to distinguish anti-native (anti-nHLA) from anti-dHLA. Sera from 280 class I HLA-sensitized SAFB-positive kidney transplant candidates were retested with acid-treated SAFB and iBeads. Concordance between SAFB and iBeads, taking into account acid-treatment results, was described at global and locus levels...
September 2015: Human Immunology
C B Bub, A C Gonçalez, M L Barjas-Castro, L C D M Sousa, S J H do Monte, V Castro
BACKGROUND AND OBJECTIVES: Transfusion support for immune-mediated platelet refractoriness (PR) is clinically challenging, technically laborious and costly. The development of 'EpHLA/EpVix software' has been used successfully to select kidney donors. Here, we sought to evaluate this new software as a tool for platelet virtual crossmatch (VxM). MATERIALS AND METHODS: This is a prospective study from 2007 to 2014 of PR patients in a tertiary hospital. Platelet components selected by HLAMatchmaker program were crossmatched by EpHLA/EpVix, anti-human globulin complement-dependent lymphocytotoxicity test (AHG-CDC), flow cytometry platelet crossmatch (FCxM) and then compared...
January 2016: Vox Sanguinis
Sussie Shrestha, Lisa Bradbury, Matthew Boal, James P Blackmur, Christopher J E Watson, Craig J Taylor, John L R Forsythe, Rachel Johnson, Lorna P Marson
BACKGROUND: Prolonged cold ischemia time (CIT) is associated with a significant risk of short- and long-term graft failure in deceased donor kidney transplants across the world. The aim of this prospective longitudinal study was to determine the importance of logistical factors on CIT. METHOD: Data on 1763 transplants were collected prospectively over 14 months from personnel in 16 transplant centers, 19 histocompatibility and immunogenetics laboratories, transport providers, and National Health Service Blood and Transplant...
February 2016: Transplantation
James P Bosanquet, Chad A Witt, Bradford C Bemiss, Derek E Byers, Roger D Yusen, Alexander G Patterson, Daniel Kreisel, Thalachallour Mohanakumar, Elbert P Trulock, Ramsey R Hachem
BACKGROUND: Allosensitization can be a significant barrier to transplantation for some patients, and previous studies suggested that pre-transplant allosensitization was associated with worse outcomes after lung transplantation. However, human leukocyte antigen (HLA) antibody testing has evolved significantly over the past 10 years, and current assays are highly sensitive and specific. METHODS: We examined the impact of pre-transplant allosensitization on post-transplant outcomes in the era of solid-phase multiplex HLA antibody detection assays in this retrospective, single-center study of 304 adult transplant recipients between January 1, 2006, and December 31, 2012...
November 2015: Journal of Heart and Lung Transplantation
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