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https://www.readbyqxmd.com/read/28832450/hla-population-genetics-in-solid-organ-transplantation
#1
Evan P Kransdorf, Marcelo J Pando, Loren Gragert, Bruce Kaplan
HLAs are fundamental to the adaptive immune response and play critical roles in the cellular and humoral response in solid organ transplantation. The genes encoding HLA proteins are the most polymorphic within the human genome, with thousands of different allelic variants known within the population. Application of the principles of population genetics to the HLA genes has resulted in the development of a numeric metric, the calculated panel-reactive antibody (CPRA) that predicts the likelihood of a positive crossmatch as a function of a transplant candidate's unacceptable HLA antigens...
September 2017: Transplantation
https://www.readbyqxmd.com/read/28777478/a-simplified-method-of-calculating-cpra-for-kidney-allocation-application-in-hong-kong-a-retrospective-study
#2
Yuen Piu Chan, Monica W K Wong, Lydia W M Tang, Mengbiao Guo, Wanling Yang, Patrick Ip, Philip K T Li, Chi Bon Leung, Ka Foon Chau, Johnny C K Lam, Nicholas K M Yeung, Janette S Y Kwok
Calculated panel reactive antibody (cPRA) represents possibility of encountering an incompatible donor for organ transplant candidates and has gradually replaced traditional PRA as a measurement of sensitization level. We tested two cPRA calculation methods on a cohort of renal candidate (n = 613). HLA typing of 563 Chinese deceased renal donors was used to estimate allele and haplotype frequencies of Hong Kong donor pool. The OPTN formula was adopted to generate cPRA (cPRA (freq)). We also incorporated a computer script to compare unacceptable antigens of patients against HLA phenotype of donors...
August 4, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28667033/percent-cpra-calculated-panel-reactive-antibody-value-predicts-percent-of-positive-platelet-crossmatches
#3
Soumya Pandey, Eric Rosenbaum, Michele Cottler-Fox, Terry O Harville
BACKGROUND: Platelet refractoriness or lack of platelet increase after platelet transfusion is seen in patients receiving chronic platelet transfusion support. Antibodies may develop against human platelet antigens (HPA) and/or against HLA class I antigens. Crossmatch (XM) compatible platelets or HLA-identical or HLA-compatible platelets are typically used to manage transfusion refractoriness. We aimed to determine if percent calculated Panel Reactive Antibody (% cPRA) against class I HLA antigens could predict percent positive platelet XM when looking for compatible transfusion products...
May 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28597555/harnessing-scientific-and-technological-advances-to-improve-equity-in-kidney-allocation-policies
#4
A R Tambur, B Audry, C Antoine, C Suberbielle, D Glotz, C Jacquelinet
We reported that current assignment of HLA-DQ is a barrier to organ allocation. Here we simulated the impact of incorporating HLA-DQ antigens and antibodies as A/B and αβ allelic variants, respectively, on calculated panel reactive antibody (cPRA) and probability of finding potential compatible donors (PCD). A cohort of 1224 donors and 2075 sensitized candidates was analyzed using HLA-DQαβ allelic (study) versus serologic (current practice) nomenclature. A significant (p < 10(-4) ) decrease in cPRA was observed with higher impact for male versus female, and first transplant versus retransplant (p < 10(-4) ), affecting mostly patients with moderate cPRA (30-80%)...
June 8, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28553286/assessment-of-spanish-panel-reactive-antibody-calculator-and-potential-usefulness
#5
Esther Asensio, Marcos López-Hoyos, Íñigo Romón, Jesús Ontañón, David San Segundo
BACKGROUND AND OBJECTIVES: The calculated panel reactive of antibodies (cPRAs) necessary for kidney donor-pair exchange and highly sensitized programs are estimated using different panel reactive antibody (PRA) calculators based on big enough samples in Eurotransplant (EUTR), United Network for Organ Sharing (UNOS), and Canadian Transplant Registry (CTR) websites. However, those calculators can vary depending on the ethnic they are applied. Here, we develop a PRA calculator used in the Spanish Program of Transplant Access for Highly Sensitized patients (PATHI) and validate it with EUTR, UNOS, and CTR calculators...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28348361/the-impact-of-donor-specific-anti-human-leukocyte-antigen-hla-antibody-rebound-on-the-risk-of-antibody-mediated-rejection-in-sensitized-kidney-transplant-recipients
#6
Kyo Won Lee, Jae Berm Park, Chan Woo Cho, Nuri Lee, Heejin Yoo, Kyunga Kim, Hyojun Park, Eun Suk Kang, Wooseong Huh, Sungjoo Kim
BACKGROUND Donor-specific anti-HLA antibody (DSA) detected on Luminex-based single antigen assay (LSA) has become the subject of desensitization based upon the results of previous studies. We retrospectively investigated the impact of preoperative DSA on the incidence of antibody mediated rejection (AMR) in patients desensitized using a protocol based on rituximab and rabbit antithymocyte globulin (rATG). MATERIAL AND METHODS Nine patients (Group 1, 9/327, 2.8%) were complement dependent cytotoxicity crossmatch (CDC-XM) positive and underwent desensitization with rituximab (375 mg/m²), intravenous immunoglobulin (IVIG; 400 mg/kg), plasmapheresis, and rATG...
March 28, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28340809/corrected-panel-reactive-antibody-positivity-rates-for-hypersensitized-patients-in-turkish-population-with-calculated-panel-reactive-antibody-software
#7
S T Karadeniz, S U Akgul, Y Ogret, H S Ciftci, A Bayraktar, H Bakkaloglu, Y Caliskan, K Yelekci, A Turkmen, A E Aydin, F S Oguz, M Carin, F Aydin
INTRODUCTION: High rates of panel-reactive antibody (PRA) may decrease the chance of kidney transplantation and may result in long waiting periods before transplantation. The calculated PRA (cPRA) is performed based on unacceptable HLA antigens. These antigens are identified by a program that was created based on the antibodies that developed against the HLA antigens circulating in serum and on the risk of binding of these antibodies to antigens. The antigen profile of the population and antigen frequencies can be measured, and more realistic cPRA positivity rates may be obtained using this method...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28318744/calculated-panel-reactive-antibody-predicts-outcomes-on-the-heart-transplant-waiting-list
#8
Evan P Kransdorf, Michelle M Kittleson, Jignesh K Patel, Marcelo J Pando, D Eric Steidley, Jon A Kobashigawa
BACKGROUND: Sensitized heart transplant candidates spend more time and have higher mortality on the waiting list. Although the calculated panel-reactive antibody (CPRA) value is used to assign allocation priority to kidney transplant candidates in the United States, the relationship between CPRA and outcomes on the heart transplant waiting list is unknown. METHODS: A data set of patients listed for heart transplant with unacceptable human leukocyte antigens (HLA) entered was obtained from the United Network for Organ Sharing...
February 17, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28284304/kidney-paired-exchange-and-desensitization-strategies-to-transplant-the-difficult-to-match-kidney-patients-with-living-donors
#9
REVIEW
Thomas A Pham, Jacqueline I Lee, Marc L Melcher
With organs in short supply, only a limited number of kidney transplants can be performed a year. Live donor donation accounts for 1/3rd of all kidney transplants performed in the United States. Unfortunately, not every donor recipient pair is feasible because of Human leukocyte antigen (HLA) sensitization and ABO incompatibility. To overcome these barriers to transplant, strategies such as kidney paired donation (KPD) and desensitization have been developed. KPD is the exchange of donors between at least two incompatible donor-recipient pairs such that they are now compatible...
January 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28245084/donor-specificity-but-not-broadness-of-sensitization-is-associated-with-antibody-mediated-rejection-and-graft-loss-in-renal-allograft-recipients
#10
C Wehmeier, G Hönger, H Cun, P Amico, P Hirt-Minkowski, A Georgalis, H Hopfer, M Dickenmann, J Steiger, S Schaub
Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the "calculated population-reactive antibodies" (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor-specific HLA antibodies (DSA). Five hundred twenty-seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1-50% (n = 129), cPRA 51-100% (n = 43), and DSA (n = 105)...
August 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28162932/multicenter-evaluation-of-a-national-organ-sharing-policy-for-highly-sensitized-patients-listed-for-heart-transplantation-in-canada
#11
Brian Clarke, Anique Ducharme, Nadia Giannetti, Daniel Kim, Michael McDonald, Peter Pflugfelder, Miroslaw Rajda, Mario Sénéchal, Ellie Stadnick, Mustafa Toma, Shelley Zieroth, Debra Isaac
BACKGROUND: Transplantation of sensitized recipients has been associated with increased risk of post-transplant complications. In 2010, the Canadian Cardiac Transplant Network (CCTN) created a unique status listing for highly sensitized heart transplant candidates. Status 4S listing requires calculated panel-reactive antibody (cPRA) level >80% as the sole listing criteria and enables geographic expansion of the donor pool by providing national access. In this study, we describe patient characteristics and outcomes of those transplanted as Status 4S in Canada...
May 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28086979/b-cell-repertoires-in-hla-sensitized-kidney-transplant-candidates-undergoing-desensitization-therapy
#12
John F Beausang, H Christina Fan, Rene Sit, Maria U Hutchins, Kshama Jirage, Rachael Curtis, Edward Hutchins, Stephen R Quake, Julie M Yabu
BACKGROUND: Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. METHODS: We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28069404/calculated-panel-reactive-antibody-with-decimals-a-refined-metric-of-access-to-transplantation-for-highly-sensitized-candidates
#13
Evan P Kransdorf, Marcelo J Pando
The use of the calculated panel reactive antibody (CPRA) value and the implementation of allocation points for sensitized candidates by the United Network for Organ Sharing (UNOS) have improved access to kidney transplantation for highly sensitized candidates (98% CPRA and above). Despite this, a large population of highly sensitized candidates remain awaiting transplantation. To better define this population, we propose the use of two refinements of the standard UNOS CPRA, the CPRA with decimals or CPRAd, and the likelihood of a compatible donor (LCD)...
March 2017: Human Immunology
https://www.readbyqxmd.com/read/28009780/kidney-transplant-with-low-levels-of-dsa-or-low-positive-b-flow-crossmatch-an-underappreciated-option-for-highly-sensitized-transplant-candidates
#14
Carrie A Schinstock, Manish Gandhi, Wisit Cheungpasitporn, Donald Mitema, Mikel Prieto, Patrick Dean, Lynn Cornell, Fernando Cosio, Mark Stegall
BACKGROUND: Avoiding donor-specific antibody (DSA) is difficult for sensitized patients. Improved understanding of the risk of low level DSA is needed. METHODS: We retrospectively compared the outcomes of 954 patients transplanted with varied levels of baseline DSA detected by single antigen beads and B flow cytometric crossmatch (XM). Patients were grouped as follows: -DSA/-XM, +DSA/-XM, +DSA/low +XM, +DSA/high +XM, and -DSA/+XM and followed up for a mean of 4...
October 2017: Transplantation
https://www.readbyqxmd.com/read/27988992/outcomes-in-the-highest-panel-reactive-antibody-recipients-of-deceased-donor-kidneys-under-the-new-kidney-allocation-system
#15
Sandesh Parajuli, Robert R Redfield, Brad C Astor, Arjang Djamali, Dixon B Kaufman, Didier A Mandelbrot
Since the institution of the new kidney allocation system in December 2014, kidney transplant candidates with the highest calculated panel reactive antibodies (cPRA) of 99-100 have been transplanted at much higher rates. However, concerns have been raised that outcomes in these patients might be impaired due to higher immunological risk and longer cold ischemia times resulting from long-distance sharing of kidneys. Here, we compare outcomes at the University of Wisconsin between study patients with cPRA 99-100 and all other recipients of deceased donor kidneys transplanted between 12/04/2014 and 12/31/2015...
March 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/27955974/increased-access-to-transplantation-of-highly-sensitized-patients-under-the-new-kidney-allocation-system-a-single-center-experience
#16
Adriana I Colovai, Maria Ajaimy, Layla G Kamal, Peter Masiakos, Shirley Chan, Christina Savchik, Michelle Lubetzky, Graciela de Boccardo, Alesa Courson, Attasit Chokechanachaisakul, Jay Graham, Stuart Greenstein, Milan Kinkhabwala, Juan Rocca, Enver Akalin
We aimed to investigate the impact of the new kidney allocation system (KAS) on the rate of transplantation of sensitized patients at our center. Pre-KAS and post-KAS intervals were Jan 1st to Dec 3rd 2014 and Jan 1st 2015 to Dec 3rd 2015, respectively. The number of deceased-donor crossmatches performed by flow cytometry increased from 715 pre-KAS to 1188 post-KAS. The percent of crossmatches performed for sensitized patients with calculated panel reactive antibody (cPRA)>0% increased from 19% pre-KAS to 26% post-KAS (p<0...
March 2017: Human Immunology
https://www.readbyqxmd.com/read/27890719/casting-a-smaller-net-into-a-bigger-donor-pool-a-single-center-s-experience-with-the-new-kidney-allocation-system
#17
Julie A Houp, Karl P Schillinger, Andrew J Eckstein, Renato M Vega, Niraj M Desai, Bonnie E Lonze, Annette M Jackson
The new kidney allocation system (KAS) provides additional allocation points for candidates with broad HLA sensitization in an effort to increase transplant rates for this underserved population. Following the implementation of KAS, our center lowered the HLA antibody threshold for listing unacceptable antigens from a cytotoxicity crossmatch level to a flow cytometric crossmatch level increasing Calculated Panel Reactive Antibody (CPRA) values and allocation points, yet restricting acceptable donor HLA phenotypes...
January 2017: Human Immunology
https://www.readbyqxmd.com/read/27801681/immunological-effect-of-skin-allograft-in-burn-treatment-impact-on-future-vascularized-composite-allotransplantation
#18
Rebecca M Garza, Barry H Press, Dolly B Tyan, Yvonne L Karanas, Gordon K Lee
Skin allografts are the gold standard in temporary burn wound coverage, but allografts are hypothesized to place a high antigenic load on recipients. This project aims to determine the degree of human leukocyte antigen sensitization in burn patients treated with allografts. Serum was obtained from nine adult, nontransfused, and nontransplanted burn patients treated with allografts. Group 1 included patients tested in the acute burn period, while group 2 included different patients tested months to years after injury...
May 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/27647555/low-transplantability-of-0-blood-group-and-highly-sensitized-candidates-in-the-portuguese-kidney-allocation-algorithm-quantifying-an-old-problem-in-search-of-new-solutions
#19
S Tafulo, J Malheiro, L Dias, C Mendes, E Osório, L S Martins, J Santos, S Pedroso, M Almeida, A Castro-Henriques
The impact of patient's biological differences in waiting time for kidney transplantation is well known and has been a subject of extensive debate and struggle in transplantation community. Our purpose was to evaluate patient's access to kidney transplantation in Portugal, regarding their degree of allosensitization and blood type. A retrospective cohort study including 1020 candidates for kidney transplantation between 01 January 2010 and 31 December 2011 in transplant unit Centro Hospitalar do Porto was performed...
November 2016: HLA
https://www.readbyqxmd.com/read/27569922/estimating-waiting-time-for-deceased-donor-renal-transplantion-in-the-era-of-new-kidney-allocation-system
#20
F Torlak, M U S Ayvaci, M E Ahsen, C Arce, M A Vazquez, B Tanriover
BACKGROUND: On December 4, 2014, a new deceased donor kidney allocation system (KAS) was implemented. The KAS was designed to improve organ equity and graft-recipient longevity matching. However, estimated wait-time to deceased donor transplantation is difficult to predict post-KAS. METHODS: Using the Kidney-Pancreas Simulated Allocation Model software (KPSAM), a program that the Organ Procurement and Transplant Network uses to assess policy proposals, we compared the kidney allocations of both the new (post-KAS) and old policies (pre-KAS) (10 iterations for each group; total N = 204,148) and estimated wait-time based on blood type, duration of dialysis exposure, and calculated panel-reactive antibody (CPRA)...
July 2016: Transplantation Proceedings
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