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Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study

3/3/2020

 
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The first universal algorithm for predicting the risk of kidney transplant loss, named iBox, has been developed, validated and just made public by teams from Europe and the US.

​The iBox is designed for clinicians to personalize and improve patient follow-up. The iBox could also accelerate the development of new immunosuppressive treatments by reducing the duration of clinical trials and defining a valid surrogate endpoint.
Chronic kidney disease affects 1 out of 10 people worldwide and is steadily increasing. When it reaches end-stage renal disease and endangers the lives of patients, dialysis or transplantation is required. ​

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2019 AIMed Abstract Competition Winner Series: Marc Raynaud

1/23/2020

 
​AIMed encouraged anyone who has innovative ideas of how artificial intelligence (AI) will transform the future of medicine and healthcare, to participate in our annual Abstract Competition.

​For 2019, the winner is 
Marc Raynaud in the category "Decision Support and Hospital Monitoring" with his abstract "Multidimensional system to dynamically predict graft survival after kidney transplantation"
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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.
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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.

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KIDNEY WEEK 2019: PTG at ASN meeting 2019

10/15/2019

 
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The Kidney Week is a periodic and international ASN meeting that gathers thousands of kidney professionals from across the globe. For the 2019 event, the event is held in Washington, DC between the 5th to the 10th of November 2019. 

Three of the Paris Transplant Group members will have the opportunities to present the latest results of the Group including the latest published information about the iBox algorithm.

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Presentation to nobel laureate Alvin Roth

9/20/2019

 
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Alexandre Loupy gave a lecture at Stanford University at the invitation of the Nobel Prize laureate Alvin Roth. To the audience, including F Javier Carmona, Alexandre Loupy presented the transplantation allocation systems and the iBox results recently published in BMJ.

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PTG awarded the ESOT StrongeR Together Pro Award

9/16/2019

 
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The team of the Paris Transplant Group has been awarded at the ESOT 2019 congress in Copenhagen for its many contribution in the field of transplantation. 

The Prize is given to a single Institution having submitted at least 5 abstracts for the event and granted with the best score. The Paris Transplant Group is very pleased to won this European award twice in a row. 

Check out the contribution submitted by the Group on the ESOT website: esotcongress.org.

Olivier Aubert GRANTED with the ESOT Young Investigator Award 2019

9/15/2019

 
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At the ESOT 2019, Olivier Aubert has been awarded of the ESOT Young Investigator Award (YIA).

The prize is a recognition of one of the best works, submitted to the ESOT2019, on the basis of the quality of their contribution to donation and/or transplantation, as well as the highest score. ​
Olivier Aubert is awarded for its work on "Disparities in the acceptance of deceased donor kidney and consequences for transplant access: nationwide analysis of practice in the US and France". The co-authors of this work are affiliated to Paris Translational Center for Organ Transplantation,  the University of Pennsylvania, Philadelphia, US ;  the Agence de la Biomédecine of France and two Parisian transplantation centres: Necker Hospital and Saint Louis Hospital.

Find more information about the study in the article published in the JAMA journal: access the full study.

Disparities in Acceptance of Deceased Donor Kidneys Between the United States and France and Estimated Effects of Increased US Acceptance

8/26/2019

 
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New publication in JAMA Internal Medicine: The first international analysis of renal transplant patient data shows that a change in allocation criteria in the United States could benefit patients on the waiting list. Thousands more kidneys could be transplanted each year if the United States used, as France does, kidneys from older donors.
Nearly 5,000 people in the United States and 3,500 in Europe die each year waiting for a kidney transplant. Yet, over the same period, in the United States, more than 3,500 available kidneys were discarded. The Journal of the American Medical Association (JAMA) Internal Medicine today published our results, obtained with the help of an international team, that compared the use of kidneys available in the United States and France between 2004 and 2014. ​
Using a new approach based on validated analytical methods and computer simulations, this work revealed that French transplant centres are much more likely to transplant kidneys from older donors than their American counterparts, and that this effectively increases the number of patients transplanted. 

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PTG at ESOT2019

6/18/2019

 
From 15 to 18 September 2019 the annual event of the European Society for Organ Transplantation (ESOT) takes place in Copenhagen.

ESOT is the European umbrella organisation under which all European transplant professionals are organized. The organisation trains and supports its members through various European programmes and events, such as the 2019 event in Copenhagen.
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During the event, a specific symposium is held for the EU Train-ESOT that highlights the methodological and statistical risks clinical researchers can face in the field of transplantation. Carmen Lefaucheur, Olivier Aubert, Alexandre Loupy, Yassine Bouatou, Dany Anglicheau and Christophe Legendre are invited to speak during this event to present the future of patient care in transplantation.
Check the poster submitted by Marc Raynaud here. 

You can follow the event through social media with the hashtag #ESOT2019 and @ParisTxGroup.

PTG at the 2019 ATC in Boston

5/14/2019

 
The American Transplant Congress, or ATC, is the not-to-be-missed event to exchange new scientific and clinical information from the field of transplantation.

​Each year, transplant physicians, scientists, nurses, organ procurement personnel, pharmacists, allied health professionals, and other transplant professionals gather in this congress organized by the American Society of Transplant Surgeons and the American Society of Transplantation.
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All aboard the EU-TRAIN at ESOT2019

5/2/2019

 
The first EU TRAIN – ESOT symposium takes place at the ESOT2019 Congress in Copenhagen.

This is a unique opportunity to “get on board” the EU-TRAIN, the European Transplantation and Innovation Consortium for Risk Stratification in Kidney Transplant Patients. 
​
The symposium will not only introduce the consortium, but it will also focus on the methodological and statistical pitfalls clinical researchers can face in the field of transplantation.
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Archetype Analysis Identifies Distinct Profiles in Renal Transplant Recipients with Transplant Glomerulopathy Associated with Allograft Survival

3/14/2019

 
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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.

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The 2019 BANFF Meeting

2/27/2019

 
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This year, the BANFF Foundation for Allograft Pathology partners up with the American Society of Histocompatibility and Immunogenetics (ASHI) for a joint scientific meeting. Which will take place between the 23rd and the 27th of September in Pittsburgh, USA. Dr. Alexandre Loupy will be present there as part of the ASHI/BANFF Steering Committee.
Abstract submissions are now open for oral and poster presentations. The deadline for the submission is the 8th of April.

During the meeting, you will be able to meet more than 1 200 professionals in HLA and the transplant field. And discover all the latest updates in immunogenetics and transplant immunology.

The BANFF Foundation for Allograft Pathology is a non-profit foundation, established in 2013. BANFF aims to further the development of the international BANFF Classification of Allograft Pathology, as well as publicize it. They also aspire to ease collaborative research in order to improve the care of transplant patient.

ASHI was founded in 1974, it is a non-profit international organization of clinical and research professionals. ASHI aims to advance the science and application of histocompatibility and immunogenetics. They also want to provide a forum for the exchange of information among scientists.

Alexandre Loupy, winner of the 2018 National Academy of Medicine Award

12/19/2018

 
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On December 18, 2018, Dr. Alexandre Loupy was awarded the National Academy of Medicine Award for his work on "Renal transplantation, anti-HLA graft rejection, and biomarker identification".

This is the first time he has received a national award for his research in France. They have made it possible to develop the international classification of graft rejection in recent years. With the goal of improving the management of transplant patients.

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PTG at the annual congress of SFT

12/3/2018

 
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The Société Francophone de Transplantation (SFT) will host solid organ transplant specialists in Toulouse, France from December 4 to 7, 2018. Several members of the Paris Transplant Group are present at the event.

The SFT Annual Congress, which is meeting this year for the 18th time, is the must-attend event for transplant professionals in France.  Intended for all medical and paramedical people involved in transplantation, the Congress allows internationally renowned speakers to share the latest medical advances in the field.

The event is organized by Toulouse University Hospital, which is a partner of the KTD-innov project. 

Antibody-Mediated Rejection of Solid-Organ Allografts

9/20/2018

 
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End-stage organ diseases are responsible for millions of deaths worldwide each year. Organ transplantation has become the treatment of choice, but despite the 120,000 new organ transplantations performed each year, only 1 million persons worldwide have functioning solid-organ transplants1 because of the lack of improvement in long-term allograft survival over the past few decades and the limited organ supply.

HLA incompatibility between donors and recipients who are not genetically identical has been identified as the main barrier to successful transplantation, mostly because of antibody-mediated rejection, a form of allograft rejection triggered by the production of antibodies directed mainly toward donor (nonself) HLA molecules. ​
This review focuses on current standards for the management of antibody-mediated rejection in transplant recipients and identifies future directions for improving diagnostics and moving toward tailored therapeutics. Such advances require the development of pathogenesis-based approaches that combine precise characterization of the biologic properties of antibodies, noninvasive biomarkers, and allograft gene-expression profiling, which will set the stage for bringing antibody-mediated rejection into the era of precision medicine.

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Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis

5/25/2018

 
Background:  
Anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are recognized as a major barrier to patients’ access to organ transplantation and the major cause of graft failure. The capacity of circulating anti-HLA DSAs to activate complement has been suggested as a potential biomarker for optimizing graft allocation and improving the rate of successful transplantations.
Methods and findingsTo address the clinical relevance of complement-activating anti-HLA DSAs across all solid organ transplant patients, we performed a meta-analysis of their association with transplant outcome through a systematic review, from inception to January 31, 2018. The primary outcome was allograft loss, and the secondary outcome was allograft rejection. A comprehensive search strategy was conducted through several databases (Medline, Embase, Cochrane, and Scopus).
A total of 5,861 eligible citations were identified. A total of 37 studies were included in the meta-analysis. Studies reported on 7,936 patients, including kidney (n = 5,991), liver (n = 1,459), heart (n = 370), and lung recipients (n = 116). Solid organ transplant recipients with circulating complement-activating anti-HLA DSAs experienced an increased risk of allograft loss (pooled HR 3.09; 95% CI 2.55–3.74, P = 0.001; I2 = 29.3%), and allograft rejection (pooled HR 3.75; 95% CI: 2.05–6.87, P = 0.001; I2 = 69.8%) compared to patients without complement-activating anti-HLA DSAs. The association between circulating complement-activating anti-HLA DSAs and allograft failure was consistent across all subgroups and sensitivity analyses. Limitations of the study are the observational and retrospective design of almost all included studies, the higher proportion of kidney recipients compared to other solid organ transplant recipients, and the inclusion of fewer studies investigating allograft rejection.
ConclusionsIn this study, we found that circulating complement-activating anti-HLA DSAs had a significant deleterious impact on solid organ transplant survival and risk of rejection. The detection of complement-activating anti-HLA DSAs may add value at an individual patient level for noninvasive biomarker-guided risk stratification.
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Cit: Antoine Bouquegneau et al.  PLoS Med. 2018 May 25;15(5):e1002572. PMID: 30052664

Complement-binding anti-HLA antibodies are independent predictors of response to treatment in kidney recipients with antibody-mediated rejection

5/22/2018

 
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A major hurdle to improving clinical care in the field of kidney transplantation is the lack of biomarkers of the response to antibody-mediated rejection (ABMR) treatment. To discover these we investigated the value of complement-binding donor-specific anti-HLA antibodies(DSAs) for evaluating the response to treatment. The study encompassed a prospective cohort of 139 kidney recipients with ABMR receiving the standard of care treatment, including plasma exchange, intravenous immunoglobulin and rituximab. Patients were systematically assessed at the time of diagnosis and three months after treatment initiation for clinical and allograft histological characteristics and anti-HLA DSAs, including their C1q-binding ability. After adjusting for clinical and histological parameters, post-treatment C1q-binding anti-HLA DSA was an independent and significant determinant of allograft loss (adjusted hazard ratio 2.57 (95% confidence interval 1.29-5.12). In 101 patients without post-treatment C1q-binding anti-HLA DSA there was a significantly improved glomerular filtration rate with significantly reduced glomerulitis, peritubular capillaritis, interstitial inflammation, tubulitis, C4d deposition, and endarteritis compared with 38 patients with posttreatment C1q-binding anti-HLA DSA. A conditional inference tree model identified five prognostic groups at the time of post-treatment evaluation based on glomerular filtration rate, presence of cg lesion and C1q-binding anti-HLA DSA (cross-validated accuracy: 0.77). Thus, circulating complement-binding anti-HLA DSAs are strong and independent predictors of allograft outcome after standard of care treatment in kidney recipients with ABMR.
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Denis Viglietti et al.
Kidney Int. 2018 Oct;94(4):773-787.
PMID: 29801667

Banff Lung Report 2017

2/5/2018

 
​The Lung session of the 2017 14th Banff Foundation for Allograft Pathology Conference, Barcelona focused on the multiple aspects of antibody-mediated rejec-tion (AMR) in lung transplantation.

​Multidimensional approaches for AMR diagnosis, including classification, histological and immunohistochemical analysis, and donor- specific antibody (DSA) characterization with their current strengths and limitations were reviewed in view of recent research.

The group also discussed the role of tissue gene expression analysis in the context of unmet needs in lung transplantation. The current best practice for monitoring of AMR and the therapeutic approach are summarized and highlighted in this report.

The working group reached consensus of the major gaps in current knowledge and focused on the unanswered questions regard-ing pulmonary AMR. An important outcome of the meeting was agreement on the need for future collaborative research projects to address these gaps in the field of lung transplantation.

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Dynamic Prognostic Score to Predict Kidney Allograft Survival in Patients with Antibody-Mediated Rejection

1/31/2018

 
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Abstract: 
No tool is available for the early assessment of response to antibody-mediated rejection (ABMR) therapies in kidney allograft recipients. This study was designed to define a dynamic composite prognostic ABMR score to predict kidney allograft survival, integrating the disease characteristics at diagnosis and the response to treatment. Among 1978 kidney recipients who underwent transplant between 2008 and 2014, we included 278 patients diagnosed with active ABMR and receiving standard treatment, including plasma exchange, intravenous Ig, and rituximab. Patients were prospectively assessed at diagnosis and after treatment for clinical data, histologic characteristics (allograft biopsy specimen), and donor-specific anti-HLA antibodies (DSA). The dynamic ABMR prediction model included GFR (P<0.001) and presence of interstitial fibrosis/tubular atrophy (P=0.003) at diagnosis and changes in GFR (P<0.001), peritubular capillaritis Banff score(P=0.002), and DSA mean fluorescence intensity (P<0.001) after treatment. Overall, this model showed good calibration and discrimination (C-statistic=0.84). The ABMR prognostic score derived from the prediction model identified three risk strata with 6-year kidney allograft survival rates of 6.0% (high-risk group, n=40), 44.9% (intermediate-risk group, n=36), and 84.4% (low-risk group, n=202), and it provided greater net clinical benefit to patients than did considering them all to have the same level of risk of allograft loss. The performance of the ABMR prognostic score was validated in an independent cohort of 202 kidney recipients with ABMR (C-statistic=0.79). The ABMR prognostic score could be used to inform therapeutic decisions in clinical practice and for the design of clinical trials.
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Denis Viglietti et al.
J Am Soc Nephrol. 2018 Feb;29(2):606-619.
PMID: 29255058

The Banff 2017 Kidney Meeting Report

12/15/2017

 
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​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.

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

11/9/2017

 
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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.
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J Heart Lung Transplant. 2017 Nov;36(11):1192-1200
PMID:28662985

T cell-mediated rejection is a major determinant of inflammation in scarred areas in kidney allografts.

10/31/2017

 
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Carmen Lefaucheur et al
Am J Transplant.
 2018 Feb;18(2):377-390.
PMID: 29086461
​Abstract
Inflammation in fibrosis areas (i-IF/TA) of kidney allografts is associated with allograft loss; however, its diagnostic significance remains to be determined. We investigated the clinicohistologic phenotype and determinants of i-IF/TA in a prospective cohort of 1539 kidney recipients undergoing evaluation of i-IF/TA and tubulitis in atrophic tubules (t-IF/TA) on protocol allograft biopsies performed at 1 year posttransplantation. We considered donor, recipient, and transplant characteristics, immunosuppression, and histological diagnoses in 2260 indication biopsies performed within the first year posttransplantation. Nine hundred forty-six (61.5%) patients presented interstitial fibrosis/tubular atrophy (IF/TA Banff grade > 0) at 1 year posttransplant, among whom 394 (41.6%) showed i-IF/TA. i-IF/TA correlated with concurrent t-IF/TA (P < .001), interstitial inflammation (P < .001), tubulitis (P < .001), total inflammation (P < .001), peritubular capillaritis (P < .001), interstitial fibrosis (P < .001), and tubular atrophy (P = .02). The independent determinants of i-IF/TA were previous T cell-mediated rejection (TCMR) (P < .001), BK virus nephropathy (P = .007), steroid therapy (P = .039), calcineurin inhibitor therapy (P = .011), inosine-5'-monophosphate dehydrogenase inhibitor therapy (P = .011), HLA-B mismatches (P = .012), and HLA-DR mismatches (P = .044). TCMR patients with i-IF/TA on posttreatment biopsy (N = 83/136, 61.0%) exhibited accelerated progression of IF/TA over time (P = .01) and decreased 8-year allograft survival (70.8% vs 83.5%, P = .038) compared to those without posttreatment i-IF/TA. Our results support that i-IF/TA may represent a manifestation of chronic active TCMR.
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Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to Treatment

10/17/2017

 
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Carmen Lefaucheur et al
JASN February 2018, 29 (2) 620-635
PMID: 29042454
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Abstract
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNγ response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.

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

9/24/2017

 
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​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.

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