Port-Saint-Louis-du-Rhône, France
Port-Saint-Louis-du-Rhône, France

Time filter

Source Type

Haas M.,Cedars Sinai Medical Center | Sis B.,University of Alberta | Racusen L.C.,Johns Hopkins University | Solez K.,University of Alberta | And 23 more authors.
American Journal of Transplantation | Year: 2014

The 12th Banff Conference on Allograft Pathology was held in Comandatuba, Brazil, from August 19-23, 2013, and was preceded by a 2-day Latin American Symposium on Transplant Immunobiology and Immunopathology. The meeting was highlighted by the presentation of the findings of several working groups formed at the 2009 and 2011 Banff meetings to: (1) establish consensus criteria for diagnosing antibody-mediated rejection (ABMR) in the presence and absence of detectable C4d deposition; (2) develop consensus definitions and thresholds for glomerulitis (g score) and chronic glomerulopathy (cg score), associated with improved inter-observer agreement and correlation with clinical, molecular and serological data; (3) determine whether isolated lesions of intimal arteritis ("isolated v") represent acute rejection similar to intimal arteritis in the presence of tubulointerstitial inflammation; (4) compare different methodologies for evaluating interstitial fibrosis and for performing/evaluating implantation biopsies of renal allografts with regard to reproducibility and prediction of subsequent graft function; and (5) define clinically and prognostically significant morphologic criteria for subclassifying polyoma virus nephropathy. The key outcome of the 2013 conference is defining criteria for diagnosis of C4d-negative ABMR and respective modification of the Banff classification. In addition, three new Banff Working Groups were initiated. The 2013 Banff Transplant Conference defines revised, consensus criteria for acute/active and chronic, active antibody-mediated rejection in renal allograft biopsies, criteria that include C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Also see comprehensive review by Djamali et al on page 255. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.


Glotz D.,Nephrology and Transplantation Service | Chapman J.R.,University of Sydney | Dharnidharka V.R.,University of Florida | Hanto D.W.,Beth Israel Deaconess Medical Center | And 13 more authors.
Transplantation | Year: 2012

: Posttransplant lymphoproliferative disorders (PTLDs) are associated with significant morbidity and mortality among solid-organ transplant patients, but approaches to diagnosis and management vary considerably. An international multidisciplinary panel evaluated current understanding of risk factors and classification systems and developed recommendations to aid in PTLD prevention. We considered evidence on PTLD risk factors including Epstein-Barr virus serostatus and immunosuppression and identified knowledge gaps for future research. Recommendations address prophylactic and preemptive strategies to minimize PTLD development, including modulation of immunosuppression and antiviral drug regimens. Finally, new classification criteria were outlined that may help facilitate standardized reporting and improve our understanding of PTLD. © 2012 Lippincott Williams & Wilkins.


Tambur A.R.,Northwestern University | Glotz D.,Nephrology and Transplantation Service | Herrera N.D.,Northwestern University | Chatroop E.N.,Northwestern University | And 3 more authors.
Human Immunology | Year: 2016

Antibody removal therapies are used for patients with antibody-mediated-rejection or those requiring desensitization to become transplantable. Accurate measurement of antibody levels prior to, and during treatment, are required to choose the best therapeutic approach, and to provide measure of treatment efficacy. Currently, the FDA does not regard solid-phase assays for HLA-antibody identification as a reliable surrogate-marker for treatment efficacy. Serum samples from 40 patients (58 assays; >2200 positive data points) undergoing antibody-removal-therapies were tested as sample-pairs, pre- and post-treatment. MFI values of IgG and C1q single-antigen-bead assays were compared with antibody titer values (serial dilutions). Antibody reduction was tracked and the differences in pre-to-post-treatment values were calculated as delta-reduction of antibody levels. Dynamic patterns of titration studies reduced effects of serum-inherent inhibitory factors (prozone-like); eliminated over-saturation limitations, and provided better estimation of antibody-binding strength compared with the other methods. Moreover, delta-reduction of antibody values using titration studies was significantly more uniform compared with either IgG or C1q tests. Analyzing antibody results using only C1q positive or only higher MFI values did not change the overall magnitude of results. Overall, titration studies provided better estimate of responsiveness to treatment and thus can serve as companion to monitoring efficacy of antibody-removal therapies. © 2016 American Society for Histocompatibility and Immunogenetics


PubMed | Nephrology and Transplantation Service, Northwestern University and University of California at Los Angeles
Type: Journal Article | Journal: Human immunology | Year: 2016

Antibody removal therapies are used for patients with antibody-mediated-rejection or those requiring desensitization to become transplantable. Accurate measurement of antibody levels prior to, and during treatment, are required to choose the best therapeutic approach, and to provide measure of treatment efficacy. Currently, the FDA does not regard solid-phase assays for HLA-antibody identification as a reliable surrogate-marker for treatment efficacy. Serum samples from 40 patients (58 assays; >2200 positive data points) undergoing antibody-removal-therapies were tested as sample-pairs, pre- and post-treatment. MFI values of IgG and C1q single-antigen-bead assays were compared with antibody titer values (serial dilutions). Antibody reduction was tracked and the differences in pre-to-post-treatment values were calculated as delta-reduction of antibody levels. Dynamic patterns of titration studies reduced effects of serum-inherent inhibitory factors (prozone-like); eliminated over-saturation limitations, and provided better estimation of antibody-binding strength compared with the other methods. Moreover, delta-reduction of antibody values using titration studies was significantly more uniform compared with either IgG or C1q tests. Analyzing antibody results using only C1q positive or only higher MFI values did not change the overall magnitude of results. Overall, titration studies provided better estimate of responsiveness to treatment and thus can serve as companion to monitoring efficacy of antibody-removal therapies.


Tambur A.R.,Comprehensive Transplant Center | Rosati J.,Comprehensive Transplant Center | Roitberg S.,Comprehensive Transplant Center | Glotz D.,Nephrology and Transplantation Service | And 2 more authors.
Transplantation | Year: 2014

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 DQα and DQβ chains. Four examples are illustrated in detail, representing a range of different epitope landscapes. A disparity between antigen density and mean fluorescence intensity values for some alleles within an eplet group was noted, with mean fluorescence intensity values of the lowest fluorescence bead being one tenth of the highest fluorescence bead, despite the fact that the amount of antigen on these beads were not significantly different. CONCLUSION: Our data support the need for changing the manner in which HLA-DQ antigens and antibodies are evaluated for organ transplantation. The current nomenclature system does not reflect the true nature of HLA-DQ polymorphism. Moreover, epitope immunogenicity likely involves more than the mere presence of a specific eplet. Because our field contemplates the use of epitope matching as an approach to improve organ allocation and overall outcomes, it is imperative to have accurate characterization of the immunogenicity of each epitope. This will pave the way to identifying acceptable mismatches and will allow risk stratification for generating de novo HLA-DSA after transplantation. Copyright © 2014 by Lippincott Williams & Wilkins.


Tambur A.R.,Northwestern University | Herrera N.D.,Northwestern University | Haarberg K.M.K.,Northwestern University | Cusick M.F.,Northwestern University | And 4 more authors.
American Journal of Transplantation | Year: 2015

The presence of donor-specific HLA antibodies before or after transplantation may have different implications based on the antibody strength. Yet, current approaches do not provide information regarding the true antibody strength as defined by antigen-antibody dissociation rate. To assess currently available methods, we compared between neat mean fluorescence intensity (MFI) values, C1q MFI values, ethylenediaminetetraacetic acid (EDTA)-treated samples, as well as titration studies and peak MFI values of over 7000 Luminex-based single-antigen HLA antibody data points. Our results indicate that neat MFI values do not always accurately depict antibody strength. We further showed that EDTA treatment (6%) does not always remove all inhibitory factors compared with C1q or titration studies. In this study of patients presenting with multiple antibody specificities, a prozone effect was observed in 71% of the cohort (usually not affecting all antibody specificities within a single serum sample, though). Similar to titration studies, the C1q assay was able to address the issue of potential inhibition; however, its limitation is its low sensitivity and inability to detect the presence of weak antibodies. Titration studies are the only method among the approaches used in this study to provide information suggesting antigen-antibody dissociation rates and are, therefore, likely to provide better indication of true antibody strength. The authors compare several current approaches to assess HLA donor-specific antibody strength in support of risk stratification and antibody removal therapy choices, and conclude that the most granular information is obtained by performing titration studies. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.


PubMed | Nephrology and Transplantation Service
Type: Journal Article | Journal: Transplantation | Year: 2012

: Posttransplant lymphoproliferative disorders (PTLDs) are associated with significant morbidity and mortality among solid-organ transplant patients, but approaches to diagnosis and management vary considerably. An international multidisciplinary panel evaluated current understanding of risk factors and classification systems and developed recommendations to aid in PTLD prevention. We considered evidence on PTLD risk factors including Epstein-Barr virus serostatus and immunosuppression and identified knowledge gaps for future research. Recommendations address prophylactic and preemptive strategies to minimize PTLD development, including modulation of immunosuppression and antiviral drug regimens. Finally, new classification criteria were outlined that may help facilitate standardized reporting and improve our understanding of PTLD.

Loading Nephrology and Transplantation Service collaborators
Loading Nephrology and Transplantation Service collaborators