PTG
  • Home
  • Research
    • PTG Research
    • iBox technology
    • Publications
    • Collaborations
    • Granted Projects
    • Awards
    • Database access
  • Platforms
    • Technical & Analytical Platforms
  • Team
    • Current team
    • PTG alumni
  • News & Media
    • Latest news
    • Photo and Video Gallery
    • PTG in the media
  • Job offers
  • About

The Banff 2019 Kidney Meeting Reports

9/20/2020

 
The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. 

Read More

Identification and characterization of trajectories of cardiac allograft vasculopathy after heart transplantation

5/4/2020

 
Picture
Every year, tens of thousands of deaths are due to end-stage heart failure in Europe and in the US combined. Heart transplantation is the ultimate treatment, but its number is dramatically limited due to the shortage of organs in those countries. 
​
​In the same time, the chances of survival beyond one year after transplantation have remained unchanged in recent years, despite significant progress in immunosuppressive therapy and patient care.
One of the most common reasons for long-term graft failure and patient death is an accelerated form of coronary artery disease called cardiac allograft vasculopathy. It is a frequent complication that affects up to half of patients within 10 years following heart transplantation. Yet, until now, little has been known about the different evolutive profiles of cardiac allograft vasculopathy and their risk factors.

Read More

Paris Transplant Group at the SFT congress 2019

12/2/2019

 
The members of the Paris Transplant Group are present at the SFT congress which will take place from December 3, 2019 in Bordeaux, France.
Picture
Many lectures by the Paris Transplant Group are planned to present the ongoing research to the French transplant community. The presentations will cover:
  • The latest results of clinical research, including the TRANSFORM study carried out with Novartis,
  • Research on transplant prognosis for improved patient follow-up, including the iBox algorithm.
  • Advances made in understanding the mechanisms at work in the event of rejection or unsuccessful transplantation. 
This research covers kidney, lung and other transplantation.

Read More

Archetype Analysis Identifies Distinct Profiles in Renal Transplant Recipients with Transplant Glomerulopathy Associated with Allograft Survival

3/14/2019

 
Picture
New research conducted by the Paris Translational Research Center for Organ Transplantation team could help clinicians determine which patients will have a disease that usually occurs after a kidney transplant and which are at high risk of transplant failure. The results are published today in the prestigious Journal of the American Society of Nephrology (JASN).

Transplant glomerulopathy was first described and characterized 50 years ago. It is a disease associated with the loss of a kidney transplant and common after a transplant. It affects the functional units (i. e. glomeruli) of the transplanted kidney. There is currently no treatment for this heterogeneous disease.

Read More

The Banff 2017 Kidney Meeting Report

12/15/2017

 
Picture
​REVISED DIAGNOSTIC CRITERIA FOR CHRONIC ACTIVE T CELL–MEDIATED REJECTION, ANTIBODY‐MEDIATED REJECTION, AND PROSPECTS FOR INTEGRATIVE ENDPOINTS FOR NEXT‐GENERATION CLINICAL TRIALS
​The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) and its relationship to T cell-mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody-mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i-IFTA is associated with reduced graft survival. Furthermore, these groups presented that i-IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i-IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor-specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next-generation clinical trials.

Read More

Building a tissue-based molecular diagnostic system in heart transplant rejection: The heart Molecular Microscope Diagnostic (MMDx) System.

11/9/2017

 
Picture
Abstract
Halloran PF, Potena L, Van Huyen JD, Bruneval P, Leone O, Kim DH, Jouven X, Reeve J, Loupy A.

The emergence of molecular systems offers opportunities for improving the assessment of rejection in heart transplant biopsy specimens. The present study developed a microarray-based system for assessing heart transplant endomyocardial biopsy (EMB) specimens.
We analyzed 331 protocol or for-cause EMB specimens from 221 subjects in 3 centers (Edmonton, Bologna, and Paris). Unsupervised principal component analysis (PCA) and archetype analysis used rejection-associated transcripts (RATs) shown in kidney transplants to be associated with antibody-mediated rejection (ABMR) or T cell-mediated rejection (TCMR), or both. To compare EMB specimens to kidney biopsy specimens, rejection status in both was simplified to TCMR, ABMR, or no rejection.
The pattern of RAT expression was similar in EMB and kidney specimens, permitting use of RATs to assign scores and group ("cluster") membership to each EMB, independent of histology. Three clusters emerged in EMB specimens, similar to kidney specimens: TCMR, ABMR, and no rejection. This permitted each EMB specimen to be given 3 scores and assigned to 1 cluster by its highest score. There was significant agreement between molecular phenotype-archetype scores or clusters-and both histologic diagnoses and donor-specific antibody. Area under curve estimates for predicting histologic TCMR, ABMR, and no rejection by molecular assessment were lower in EMB specimens than in kidney specimens, reflecting more uncertainty in EMB specimens, particularly in histologic diagnosis of TCMR.
Rejection-associated transcripts can be used to estimate the probability of TCMR and ABMR in heart transplant specimens, providing a new dimension to improve the accuracy of diagnoses and an independent system for recalibrating the histology guidelines.
Picture
J Heart Lung Transplant. 2017 Nov;36(11):1192-1200
PMID:28662985

European Society of Organ Transplantation (ESOT) Congress 2017 - Our abstracts

9/24/2017

 
Picture

​Sunday September 24, 2017

1/ MOLECULAR CORRELATES OF ENDOTHELIAL MTOR ACTIVATION IN HEART TRANSPLANT RECIPIENTS
Session: “ Basic and translational immunology” (17:45 to 18:45)
Location: Room 118 + 119 – 18:29 

M Racapé, A Loupy, J Reeve, J Venner , R Guillemain, L Hidalgo, C Lefaucher, X Jouven, P Bruneval, J Duaong Van Huyen, P Halloran 
Background
The detection of phosphorylated effectors of the mTOR pathway such as phosphorylated-S6RP in endothelial cells by immunohistochemistry (IHC) has been associated with Antibody-Mediated allograft Rejection (AMR). The aim of this study was to evaluate the molecular phenotype related to the endothelial detection of pS6RP in heart transplant recipients.
Methods
This case-control study included 41 heart transplant patients from four French referral centers with biopsy proven antibody-mediated rejection (pAMR+) and a matched control group of 30 patients without rejection (pAMR0) based on the updated ISHLT classification. From these patients, 94 endomyocardial biopsies (EMB) had adequate material for microarray analysis and endothelial expression analysis of pS6RP by IHC. We also determined the allograft gene expression profile using the ABMR molecular score in addition to pathogenesis-based transcripts reflecting endothelial activation (DSAST and ENDAT), macrophage burden (QCMAT), gamma-interferon response (GRIT) and NK-cell burden (NKB) (http://atagc.med.ualberta.ca).
Results
Among the 94 EMBs included in the main analyses, 50 were pAMR+ (53.2%) and 44 (46.8%) were pAMR0 normal EMBs. Endothelial expression of pS6RP was observed in 27/50 (54%) of pAMR+ biopsies and 12 out of 44 normal biopsies (27.3%, Fischer's exact: p=0.012). As compared with biopsies without pS6RP labeling, biopsies with pS6RP staining showed increased expression of DSAST (Mann-Whitney: p<0.0001), ENDAT (p=0.0009), QCMAT (p=0.0046), NKB (p=0.0001), GRIT (p=0.0008) and increased ABMR molecular score reflecting AMR injury (p=0.0001).
Conclusion
Endothelial activation of mTOR pathway is associated with AMR and increased expression in transcripts reflecting endothelial activation, macrophage burden, microcirculation and NK burden. Our results suggest the importance of the mTOR pathway activation in AMR injury and the potential interest of using mTOR inhibitors in this setting.

Read More

Circulating donor-specific anti-HLA antibodies are a major factor in premature and accelerated allograft fibrosis.

9/7/2017

 
Picture
Abstract
Addressing the causes of kidney allograft-accelerated aging is an important challenge for improving long-term transplant outcomes. Here we investigated the role of circulating donor-specific anti-HLA antibodies (HLA-DSAs) in the development and the progression of kidney allograft fibrosis with inclusion of traditional risk factors for allograft fibrosis. We prospectively enrolled 1539 consecutive kidney recipients transplanted in two centers and assessed interstitial fibrosis and tubular atrophy (IF/TA) in biopsies performed at one year post-transplantation. The HLA-DSAs and all traditional determinants of IF/TA were recorded at transplantation and within the first year post-transplantation, including histological diagnoses in 2260 "for cause" biopsies. This identified 498 (32%) patients with severe IF/TA (Banff IF/TA grade 2 or more). HLA-DSAs were significantly associated with severe IF/TA (adjusted odds ratio, 1.53; 95% confidence interval 1.16-2.01) after including 37 determinants. HLA-DSAs remained significantly associated with severe IF/TA in patients without antibody-mediated rejection (adjusted odds ratio 1.54; 1.11-2.14). HLA-DSAs were the primary contributor, being involved in 11% of cases, while T cell-mediated rejection, calcineurin-inhibitor toxicity, acute tubular necrosis, pyelonephritis, and BK virus-associated nephropathy were involved in 9%, 8%, 6%, 5%, and 4% of cases, respectively. One hundred fifty-four patients with HLA-DSA-associated severe IF/TA showed significantly increased microvascular inflammation, transplant glomerulopathy, C4d deposition in capillaries, and decreased allograft survival compared to 344 patients with severe IF/TA without HLA-DSAs. Three hundred seventy-eight patients with post-transplant HLA-DSAs exhibited significantly accelerated progression of IF/TA compared to 1161 patients without HLA-DSAs in the biopsies performed at one year post-transplant and beyond. Thus, circulating HLA-DSAs are major determinants of premature and accelerated allograft fibrosis acting independently of traditional risk factors and antibody-mediated rejection.

Authors: Gosset C, Viglietti D, Rabant M, Vérine J, Aubert O, Glotz D, Legendre C, Taupin JL, Duong Van-Huyen JP, Loupy A, Lefaucheur C.
Picture
Kidney Int. 2017 Sep;92(3):729-742.
PMID: 28554738 ​

Real Time Central Assessment of Kidney Transplant Indication Biopsies by Microarrays: The INTERCOMEX Study

4/27/2017

 
Picture
​Am J Transplant. 2017 Nov;17(11):2851-2862.
PMID: 28449409 
Abstract
Halloran PF, Reeve J, Akalin E, Aubert O, Bohmig GA, Brennan D, Bromberg J, Einecke G, Eskandary F, Gosset C, Duong Van Huyen JP, Gupta G, Lefaucheur C, Malone A, Mannon RB, Seron D, Sellares J, Weir M, Loupy A.

​The authors conducted a prospective trial to assess the feasibility of real time central molecular assessment of kidney transplant biopsy samples from 10 North American or European centers. Biopsy samples taken 1 day to 34 years posttransplantation were stabilized in RNAlater, sent via courier overnight at ambient temperature to the central laboratory, and processed (29 h workflow) using microarrays to assess T cell- and antibody-mediated rejection (TCMR and ABMR, respectively). Of 538 biopsy samples submitted, 519 (96%) were sufficient for microarray analysis (average length, 3 mm). Automated reports were generated without knowledge of histology and HLA antibody, with diagnoses assigned based on Molecular Microscope Diagnostic System (MMDx) classifier algorithms and signed out by one observer. Agreement between MMDx and histology (balanced accuracy) was 77% for TCMR, 77% for ABMR, and 76% for no rejection. A classification tree derived to provide automated sign-outs predicted the observer sign-outs with >90% accuracy. In 451 biopsy samples where feedback was obtained, clinicians indicated that MMDx more frequently agreed with clinical judgment (87%) than did histology (80%) (p = 0.0042). In 81% of feedback forms, clinicians reported that MMDx increased confidence in management compared with conventional assessment alone. The authors conclude that real time central molecular assessment is feasible and offers a useful new dimension in biopsy interpretation. ClinicalTrials.gov NCT#01299168.

Read More

Molecular Assessment of Microcirculation Injury in Formalin-Fixed Human Cardiac Allograft Biopsies With Antibody-Mediated Rejection.

2/17/2017

 
Picture
Am J Transplant. 2017 Feb;17(2):496-505.
PMID: 27401781

Abstract
B. Afzali, E. Chapman,  M. Racapé, B. Adam,  P. Bruneval, F. Gil, D. Kim, L. Hidalgo, P. Campbell, B. Sis, J. P. Duong Van Huyen, M. Mengel.
​
Precise diagnosis of antibody-mediated rejection (AMR) in cardiac allograft endomyocardial biopsies (EMBs) remains challenging. This study assessed molecular diagnostics in human EMBs with AMR. A set of 34 endothelial, natural killer cell and inflammatory genes was quantified in 106 formalin-fixed, paraffin-embedded EMBs classified according to 2013 International Society for Heart and Lung Transplantation (ISHLT) criteria. The gene set expression was compared between ISHLT diagnoses and correlated with donor-specific antibody (DSA), endothelial injury by electron microscopy (EM) and prognosis. Findings were validated in an independent set of 57 EMBs. In the training set (n = 106), AMR cases (n = 70) showed higher gene set expression than acute cellular rejection (ACR; n = 21, p < 0.001) and controls (n = 15, p < 0.0001). Anti-HLA DSA positivity was associated with higher gene set expression (p = 0.01). Endothelial injury by electron microscopy strongly correlated with gene set expression, specifically in AMR cases (r = 0.62, p = 0.002). Receiver operating characteristic curve analysis for diagnosing AMR showed greater accuracy with gene set expression (area under the curve [AUC] = 79.88) than with DSA (AUC = 70.47) and C4d (AUC = 70.71). In AMR patients (n = 17) with sequential biopsies, increasing gene set expression was associated with inferior prognosis (p = 0.034). These findings were confirmed in the validation set. In conclusion, biopsy-based molecular assessment of antibody-mediated microcirculation injury has the potential to improve diagnosis of AMR in human cardiac transplants.

Read More

ISHLT 2016 Annual Meeting & Scientific Sessions

4/30/2016

 
Picture

Plenary session - Saturday April 30, 2016 - 10:55
Pushing New Scientific Frontiers: It’s In Our Heritage

Precision Medicine in Organ Transplantation: Moving from Off the Rack to Bespoke, Alexandre Loupy, MD, PhD, Necker Hospital, Paris, France

Abstracts -Thursday April 28, 2016 - 11:45
Molecular Correlates of Endothelial mTOR Activation in Heart Transplant Recipients

Authors
M. Racapé, A. Loupy, J. Reeve, J. Venner, R. Guillemain, L. Hidalgo, C. Lefaucheur, X. Jouven, P. Bruneval, J. Duong Van Huyen, P. Halloran. 

Abstract
  • Purpose: The detection of phosphorylated effectors of the mTOR pathway in endothelial cells by immunohistochemistry (IHC) has been associated with allograft rejection. The aim of this study was to evaluate in heart transplant recipients the molecular phenotype related to the endothelial detection of the phosphorylated effectors of the mTOR pathway, pS6RP.
  • Methods: This case-control study included 41 heart transplant patients from four French referral centers with biopsy proven antibody-mediated rejection (pAMR+) and a matched control group of 32 patients without rejection (pAMR0) based on the updated ISHLT classification. From these patients, 93 endomyocardial biopsies (EMB) had adequate material for microarray analysis and IHC. We studied in all EMB the endothelial expression of pS6RP by IHC. We also determined the allograft gene expression profile using the ABMR molecular score in addition to pathogenesis-based transcripts reflecting endothelial activation (DSAST and ENDAT), macrophage burden (QCMAT), gamma-interferon response (GRIT) and NK-cell burden (NKB) (http://atagc.med.ualberta.ca).
  • Results: Among the 93 EMBs included in main analyses, 49 were pAMR+ (52.7%) and 44 (47.3%) were pAMR0 normal EMBs. Endothelial expression of pS6RP was observed in 27/49 (55.1%) of pAMR+ biopsies and 12 out of 44 normal biopsies (27.3%, Fischer's exact: p=0.011). As compared with biopsies without endothelial pS6RP labeling, biopsies with positive endothelial pS6RP staining showed increased expression in DSAST (Mann-Whitney: p<0.0001), ENDAT (p=0.0008), QCMAT (p=0.0052), NKB (p=0.0001) and increased ABMR molecular score reflecting interferon-effects, microcirculation stress and NK burden (p=0.0001).
  • Conclusion: Endothelial activation of mTOR pathway is associated with antibody-mediated allograft rejection and increased expression in transcripts reflecting endothelial activation, macrophage burden, microcirculation and NK burden. Our results suggest the importance of the mTOR pathway activation in antibody-mediated heart allograft injury and the potential interest of using mTOR inhibitors in this setting.

    Paris Transplant Group

    Our global aim is to accelerate the translation of immunological and gene expression discoveries into the clinical field by filling the gap between basic science and applied biomedical researches.

    CATEGORIES

    Awards
    Events
    Job offers
    Press Releases
    Publications

    See also

    Press coverage
    Video and ​Picture gallery

    ALl

    All
    Alexandre Loupy
    Antoine Bouquegneau
    Antoine Durrbach
    Antoine Roux
    Awards
    Blaise Robin
    Carmen Lefaucheur
    Charlotte Debiais
    Charlotte Loheac
    Christophe Legendre
    Daniel Yoo
    Dany Anglicheau
    Denis Glotz
    Denis Viglietti
    Dina Zielinski
    Elodie Bailly
    Events
    Gillian Divard
    Guillaume Bonnet
    Guillaume Coutance
    Huanxi Zhang
    Jean Luc Taupin
    Jean Paul Duong Van Huyen
    Jean Philippe Empana
    Jessy Dagobert
    Job
    Juliette Gueguen
    Kevin Louis
    Marc Raynaud
    Marie-Cécile Bories
    Marion Rabant
    Maud Racape
    Michel Delahousse
    Olivier Aubert
    Pascal Leprince
    Patrick Bruneval
    Peter Reese
    Press Releases
    Publications
    Shaida Varnous
    Valentin Goutaudier
    Xavier Jouven
    Yassine Bouatou
    Zeynep Demir

    Archives

    October 2021
    September 2021
    August 2021
    July 2021
    February 2021
    January 2021
    December 2020
    November 2020
    October 2020
    September 2020
    August 2020
    July 2020
    May 2020
    March 2020
    January 2020
    December 2019
    October 2019
    September 2019
    August 2019
    June 2019
    May 2019
    March 2019
    February 2019
    December 2018
    September 2018
    May 2018
    February 2018
    January 2018
    December 2017
    November 2017
    October 2017
    September 2017
    June 2017
    May 2017
    April 2017
    March 2017
    February 2017
    January 2017
    December 2016
    November 2016
    June 2016
    April 2016
    October 2015
    June 2015
    August 2014
    January 2014
    September 2013
    January 2013
    June 2011
    August 2010
    May 2009

    RSS Feed

Paris Transplant Group

About PTG
PTG Team
​​Careers at PTG
​Latest News
​
Awards
Video and Picture Gallery

PTG in the Press
​Contact us

Research

iBox technology
PTG Research
PTG Publications
Covid-related research 🔓

Platforms

Technical platforms

Partnerships

Research collaborations
​Database access
​

Search

LEGAL NOTICE AND PRIVACY POLICY
© COPYRIGHT 2022. ALL RIGHTS RESERVED.

 LABS EXPLORER for the PARIS TRANSPLANT GROUP.
  • Home
  • Research
    • PTG Research
    • iBox technology
    • Publications
    • Collaborations
    • Granted Projects
    • Awards
    • Database access
  • Platforms
    • Technical & Analytical Platforms
  • Team
    • Current team
    • PTG alumni
  • News & Media
    • Latest news
    • Photo and Video Gallery
    • PTG in the media
  • Job offers
  • About