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Featured Posts (10)

  • O.O.Adebiyi, J.Gralla, P.Klem, B.Freed, S.Davis, A.C.Wiseman and J.E.Cooper

    Introduction
    The widespread utilization of single-antigen bead (SAB) assays prior to kidney transplantation has improved the detection of donor-specific antibody (DSA) in potential transplant recipients. Many studies have documented inferior renal graft outcomes in the presence of pretransplant DSA (1–15). However, the clinical importance of such DSA in the setting of a negative flow cytometry crossmatch (FCXM) at transplant remains controversial and the need for desensitization uncertain. There are limited published data regarding the impact of specific DSA characteristics such as class, strength or whether DSA persisted posttransplant on renal allograft outcomes when flow cytometry is negative. Additionally, the clinical significance…

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  • Dolores Redondo-Pachón, Julio Pascual, María J.Pérez-Sáez, Carmen García, Juan José Hernández, Javier Gimeno, Marisa Mir, Marta Crespoa

    The influence of antibodies against HLA-DP antigens detected with solid-phase assays on graft survival after kidney transplantation (KT) is uncertain.We evaluated with Luminex®the prevalence of pre- and posttransplant DP antibodies in 440 KT patients and their impact on graft survival. For 291 patients with available pretransplant samples, DP antibodies were present in 39.7% KT with pretransplant HLA antibodies and 47.7% with DSA. Graft survival of KT with pretransplant class-II DSA was worse than with non-DSA (p= 0.01). DP antibodies did not influence graft survival. Of 346 patients monitored post-KT, 17.1% had HLA class-II antibodies, 56% with DP antibodies. Class-II DSA was detected in 39%, 60.9% of them had DP antibodies. Graft survival was…

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  • Craig J.Taylor, Vasilis Kosmoliaptsis, Jessie Martin, Graham Knighton, Dermot Mallon, J. Andrew Bradley, and Sarah Peacock

    Background. Solid-phase assays to distinguish complement binding from noncomplement binding HLA-specific antibodies have been introduced, but technical limitations may compromise their interpretation. We have examined the extent to which C1q-binding to HLA-class I single-antigen beads (SAB) is influenced by denatured HLA on SAB, antibody titre, and complement interference that causes a misleading low assessment of HLA-specific antibody levels. Methods. Sera from 25 highly sensitized patients were tested using Luminex IgG-SAB and C1q-SAB assays. Sera were tested undiluted, at 1:20 dilution to detect highlevel IgG, and after ethylene diamine tetraacetic acid treatment to obviate complement interference. Conformational HLA and denatured HLA…

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  • Glen P.Westall, and Greg I.Snell

    The lung transplant community continues to struggle with the diagnosis and management of antibody-mediated rejection. The four diagnostic tenets of donor-specific antibodies, C4d staining, histopathologic changes, and allograft dysfunction, which were largely derived from the early Banff meetings on renal transplantation, have somewhat arbitrarily been applied to lung transplantation. With the passage of time, it is increasingly apparent that merits of these diagnostic pillars are less robust in lung transplantation. In this article, we summarize some of the controversies and challenges surrounding the diagnosis of antibody-mediated rejection in lung transplantation.

    Keywords: Lung transplantation, Antibody-mediated rejection, Humoral rejection, Chronic lung allograft syndrome.…

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  • Immunoassays announcement on ASHI site

    IMMUNOASSAYS WEBSITE

    In response to discussions at the 16th International Histocompatibility and Immunogenetics Workshop, members of the Johns Hopkins Immunogenetics Laboratory have created a website for all things related to solid phase antibody immunoassays.  At www.immunoassays.net, you can enter into discussions about test interpretation and troubleshooting. The site provides information on the latest assays, performance of different test lots, correlations between solid phase and cell based test results, and serum treatments.  There is information on bead assays, flow cytometry and ELISA as well as links to relevant publications. Please visit the website and become a member at www.immunoassays.net.  You can become a site moderator and lead discussions.  

    Source: …

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  • Andrea A. Zachary, Mary S. Leffell

    Summary: 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…

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  • Anat R.Tambur, Jimmy Rosati, Shirley Roitberg, Denis Glotz, John J.Friedewald and Joseph R.Leventhal

    Background. Human leukocyte antigen (HLA)-DQ has emerged as the alloantibody most frequently associated with the generation of de novo donor-specific antibody (DSA), antibody-mediated-rejection, and unfavorable transplantation outcome.
    Methods. The generation of HLA-DQ de novo DSA was interrogated in 40 transplant recipients who were immunologically naive before their failed transplantation. Eplet and epitope analyses were performed using HLAMatchmaker and Cn3D software.
    Results. Ten DQA and thirteen DQB eplets or eplet combinations were identified. All but one revealed an epitope footprint that includes both the DQa and DQb chains. Four examples are illustrated in detail, representing a range of different epitope landscapes. A disparity between antigen…

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  • B.J.Orandi, J.M.Garonzik-Wang, A.B.Massie, A.A.Zachary, J.R.Montgomery, K.J.Van Arendonk, M.D.Stegall, S.C.Jordan, J.Oberholzer, T.B.Dunn, L.E.Ratner, S.Kapur, R.P.Pelletier, J.P.Roberts, M.L.Melcher, P.Singh, D.L.Sudan, M.P.Posner, J.M.El-Amm, R.Shapiro, M.Cooper, G.S.Lipkowitz, M.A.Rees, C.L.Marsh, B.R.Sankari, D.A.Gerber, P.W.Nelson, J.Wellen, A.Bozorgzadeh, A.O.Gaber, R.A.Montgomery and D.L.Segev

    Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA). Programspecific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n¼185), positive flow, negative cytotoxic crossmatch (PFNC) (n¼536) or positive cytotoxic crossmatch (PCC) (n¼304), from 22 centers.…

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  • Annette M. Jackson, Mary S. Leffell, Robert A. Montgomery, and Andrea A. Zachary

    Purpose of review
    To identify factors that affect the choice of route to renal transplantation for the sensitized patient. The evolution of protocols for transplanting sensitized patients has been desensitization (DES), paired donation, and most recently, paired donation combined with DES. Use of these protocols has revealed various factors that influence which route is the most likely to work for a given patient.
    Recent findings
    The data indicate that patient blood type and HLA sensitization have the dominant influence on what route is best for a patient but numerous other factors, particularly the number, HLA type, and ABO type of donors a patient brings to a program will also affect the likelihood of transplantation. The distribution of these factors among patients transplanted or unable…

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  • Annette M. Jackson, Edward S. Kraus, Babak J. Orandi, Dorry L. Segev, Robert A. Montgomery and Andrea A. Zachary

    Rituximab has been used to increase the efficacy of desensitization protocols for human leukocyte antigen (HLA)-incompatible kidney transplantation; however, controlled comparisons have not been reported. Here we examined 256 post-transplant HLA antibody levels in 25 recipients desensitized with and 25 without rituximab induction, to determine the impact of B-cell depletion. We found significantly less HLA antibody rebound in the rituximab-treated patients (7% of donor-specific antibodies (DSAs) and 33% of non-DSAs) compared with a control cohort desensitized and transplanted without rituximab (32%
    DSAs and 55% non-DSAs). The magnitude of the increase was significantly larger among patients who did not receive rituximab. Interestingly,…

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