A5048658194- Renal Transplantation Outcomes and Treatments
- Transplantation: Methods and Outcomes
- Organ Transplantation Techniques and Outcomes
- Renal Diseases and Glomerulopathies
- Viral Infections and Immunology Research
- Organ Donation and Transplantation
- Renal and Vascular Pathologies
- Cytomegalovirus and herpesvirus research
- Plant and animal studies
- Animal Behavior and Reproduction
- Molecular Biology Techniques and Applications
- Evolution and Genetic Dynamics
- Mycobacterium research and diagnosis
- Gene expression and cancer classification
- Complement system in diseases
- Psoriasis: Treatment and Pathogenesis
- Systemic Sclerosis and Related Diseases
- Polyomavirus and related diseases
- Microbial infections and disease research
- T-cell and B-cell Immunology
- Spondyloarthritis Studies and Treatments
- Hepatitis C virus research
- Autoimmune and Inflammatory Disorders Research
- Inflammasome and immune disorders
- Immune Cell Function and Interaction
The Metabolomics Innovation Centre
2014-2024
University of Alberta
2013-2023
Genomics (United Kingdom)
2008-2017
Assistance Publique – Hôpitaux de Paris
2017
Inserm
2017
Université Paris Cité
2017
Hôpital Charles-Nicolle
2017
Hôpital Européen Georges-Pompidou
2017
Hôpital Laennec
2017
Hôpital Necker-Enfants Malades
2017
We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming assign cause every failure. followed 315 allograft recipients who underwent indication biopsies at 6 days 32 years posttransplant. Sixty kidneys in the follow-up period (median 31.4 months). Failure was rare T-cell-mediated rejection and acute injury common antibody-mediated or glomerulonephritis. developed rules using diagnoses, HLA antibody data explain each Excluding four...
We studied the phenotype of late kidney graft failure in a prospective study unselected transplant biopsies taken for clinical indications. analyzed histopathology, HLA antibodies and death-censored survival 234 consecutive from 173 patients, 6 days to 31 years posttransplant. Patients with (>1 year) frequently displayed donor-specific antibody (particularly class II) microcirculation changes, including glomerulitis, glomerulopathy, capillaritis, capillary multilayering C4d staining. Grafts...
Antibody-mediated rejection is the major cause of kidney transplant failure, but histology-based diagnostic system misses most cases due to its requirement for C4d positivity. We hypothesized that gene expression data could be used test biopsies presence antibody-mediated rejection. To develop a molecular test, we prospectively assigned diagnoses, including C4d-negative rejection, 403 indication from 315 patients, based on histology (microcirculation lesions) and donor-specific HLA antibody....
Export Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled (the Bortezomib Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR...
The prevalent renal transplant population presents an opportunity to observe the adaptive changes in alloimmune response over time, but such studies have been limited by uncertainties conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated (ABMR). To circumvent these limitations, we used microarrays methods investigate 703 unselected biopsies taken 3 days 35 years post-transplant from North American European centers. Using methods, diagnosed 205 specimens...
The relationship between the donor-derived cell-free DNA fraction (dd-cfDNA[%]) in plasma kidney transplant recipients at time of indication biopsy and gene expression biopsied allograft has not been defined.In prospective, multicenter Trifecta study, we collected tissue from 300 biopsies 289 to compare genome-wide with dd-cfDNA(%) corresponding samples drawn just before biopsy. Rejection was assessed microarray-based Molecular Microscope Diagnostic System using automatically assigned...
Microarrays offer potential for objective diagnosis and insights into pathogenesis of allograft rejection. We used mouse transplants to annotate pathogenesis-based transcript sets (PBTs) that reflect major biologic events in rejection—cytotoxic T-cell infiltration, interferon-γ effects parenchymal deterioration. examined the relationship between PBT expression, histopathologic lesions clinical diagnoses 143 consecutive human kidney transplant biopsies cause. PBTs correlated strongly with one...
Kidney transplant recipients that develop signs of renal dysfunction or proteinuria one more years after transplantation are at considerable risk for progression to failure. To assess the kidney this time, a "for-cause" biopsy is performed, but provides little indication as which will go on organ In an attempt identify molecules could provide information, we used microarrays analyze gene expression in 105 for-cause biopsies taken between 1 and 31 transplantation. Using supervised principal...
Abstract Objective Recent studies have shown that a nonsynonymous single‐nucleotide polymorphism (SNP) (Arg381Gln; rs11209026) in the interleukin‐23 receptor (IL‐23R) gene on chromosome 1p31 is associated with Crohn's disease and psoriasis. Given clinical immunologic overlap between ankylosing spondylitis (AS) these diseases, potential function of this candidate SNP, study was undertaken to examine association IL‐23R variants AS multiple Canadian populations. Methods We examined 3 cohorts...
The transcriptome has considerable potential for improving biopsy diagnoses. However, to realize this the relationship between molecular phenotype of disease and histopathology must be established. We assessed 186 consecutive clinically indicated kidney transplant biopsies using microarrays, built a classifier distinguish rejection from nonrejection predictive analysis microarrays (PAM). Most genes selected by PAM were interferon-gamma-inducible or cytotoxic T-cell associated, example,...
The authors conducted a prospective trial to assess the feasibility of real time central molecular assessment kidney transplant biopsy samples from 10 North American or European centers. Biopsy taken 1 day 34 years posttransplantation were stabilized in RNAlater, sent via courier overnight at ambient temperature laboratory, and processed (29 h workflow) using microarrays T cell- antibody-mediated rejection (TCMR ABMR, respectively). Of 538 submitted, 519 (96%) sufficient for microarray...
Antibody-mediated rejection (AMR) contributes to heart allograft loss. However, an important knowledge gap remains in terms of the pathophysiology AMR and how detection immune activity, injury degree, stage could be improved by intragraft gene expression profiling.We prospectively monitored 617 transplant recipients referred from 4 French centers (January 1, 2006-January 2011) for AMR. We compared patients with (n=55) a matched control group 55 without characterized all using histopathology...
Emerging molecular analysis can be used as an objective and independent assessment of histopathological scoring systems. We compared the existing Banff i-score to total inflammation (total i-) score for assessing phenotype in 129 renal allograft biopsies cause. The showed stronger correlations with microarray-based gene sets representing major biological processes during rejection. Receiver operating characteristic curves that total-i was superior (areas under 0.85 vs. 0.73 i-score, p =...
Conventional histologic diagnosis of rejection in kidney transplants has limited repeatability due to its inherent requirement for subjective assessment lesions, a rule-based system that does not acknowledge diagnostic uncertainty. Molecular phenotyping affords opportunities increased precision and improved disease classification address the limitations conventional systems quantify levels Microarray data from 1,208 transplant biopsies were collected prospectively 13 centers. Cross-validated...
Little is known regarding the molecular phenotype of kidneys with AKI because biopsies are performed infrequently. However, all kidney transplants experience acute injury, making early an excellent model provided absence rejection, donor should not have CKD, post-transplant occur relatively frequently, and follow-up typically. Here, we used histopathology microarrays to compare indication from 26 injury 11 pristine protocol stable transplants. Kidneys showed increased expression 394...
Late antibody-mediated rejection (ABMR) is a leading cause of transplant failure. Blocking IL-6 has been proposed as promising therapeutic strategy.
We previously reported a system for assessing rejection in kidney transplant biopsies using microarray-based gene expression data, the Molecular Microscope® Diagnostic System (MMDx). The present study was designed to optimize accuracy and stability of MMDx diagnoses by replacing single machine learning classifiers with ensembles diverse classifier methods. also examined use automated report sign-outs agreement between multiple human interpreters molecular results. Ensembles generated that...