- Renal Transplantation Outcomes and Treatments
- Organ Transplantation Techniques and Outcomes
- Transplantation: Methods and Outcomes
- Renal Diseases and Glomerulopathies
- Organ Donation and Transplantation
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Renal and Vascular Pathologies
- Liver Disease and Transplantation
- Blood groups and transfusion
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Diabetes and associated disorders
- Pregnancy and Medication Impact
- Complement system in diseases
- Neurological Complications and Syndromes
- Immunotherapy and Immune Responses
- Polyomavirus and related diseases
- Acute Kidney Injury Research
- Metabolism and Genetic Disorders
- Xenotransplantation and immune response
- Blood donation and transfusion practices
- Immunodeficiency and Autoimmune Disorders
- Palliative Care and End-of-Life Issues
- Immune Response and Inflammation
University of Manitoba
2016-2025
Health Sciences Centre
2008-2024
Research Manitoba
2004-2024
Manitoba Health
2014-2024
Manitoba Beekeepers' Association
2024
Canadian Blood Services
2008-2023
Alberta Health Services
2015-2022
University of British Columbia
2006-2022
Royal College of Physicians and Surgeons of Canada
2022
Children's Hospital of Eastern Ontario
2022
Standardization of renal allograft biopsy interpretation is necessary to guide therapy and establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Schema Collaborative Clinical Trials in Transplantation (CCTT) modification diagnosis pathology.Banff 97 grew from international consensus discussion begun at continued via Internet. schema (a) analysis data (b) publication experience with CCTT modification,...
The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications inflammation in areas interstitial fibrosis and tubular atrophy (i-IFTA) its relationship to T cell-mediated rejection (TCMR), continued evolution molecular diagnostics, particularly diagnosis antibody-mediated (ABMR). In confirmation previous studies, it was independently demonstrated by groups that i-IFTA is associated with reduced graft survival. Furthermore, these presented i-IFTA, when involving...
The natural history for patients with de novo donor-specific antibodies (dnDSA) and the risk factors its development have not been well defined. Furthermore, clinical histologic correlation serologic data is limited. We studied 315 consecutive renal transplants without pretransplant DSA, a mean follow-up of 6.2 ± 2.9 years. Protocol (n = 215) cause 163) biopsies were analyzed. Solid phase assays used to screen dnDSA posttransplant. A total 47 out (15%) developed at 4.6 3.0 years Independent...
The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted a new paradigm with respect to interpretation donor-specific (DSA). Although SPI assay performed on Luminex instrument (hereafter referred as assay), particular, permitted not detectable CDC, clinical...
The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of American Society Histocompatibility and Immunogenetics Pittsburgh, PA (USA) focused on refining recent updates to classification, advances from working groups, standardization molecular diagnostics. This report kidney transplant details clarifications refinements criteria chronic active (CA) T cell–mediated rejection (TCMR), borderline, antibody-mediated (ABMR). main focus sessions how address...
The prevalence of subclinical rejection, by the Banff criteria, is approximately 30% in first 3 mo renal transplant recipients. A randomized study was performed to determine whether treatment rejection with corticosteroids associated improved outcomes these patients. Seventy-two patients, stratified donor source, were biopsies at 1, 2, 3, 6, and 12 (Biopsy group), or 6- 12-mo only (Control group). Patients analyzed "intent treat" followed for a minimum 2 yr. Biopsy arm had significant...
The process of humoral rejection is multifaceted and has different manifestations in the various types organ transplants. Because this emerging as a leading cause graft loss, conference was held April 2003 to comprehensively address issues regarding rejection. Though may result from factors, discussion focused on paradigm caused by antibodies, typically against donor HLA antigens, term 'antibody-mediated rejection' (AMR). Conference deliberations were separated into four workgroups:...
De novo donor-specific antibody (dnDSA) develops in 15-25% of renal transplant recipients within 5 years transplantation and is associated with 40% lower graft survival at 10 years. HLA epitope matching a novel strategy that may minimize dnDSA development. HLAMatchmaker software was used to characterize mismatches 395 potential HLA-DR/DQ/DP conformational epitopes for 286 donor-recipient pairs. Epitope specificities were assigned using single antigen bead analysis correlated known monoclonal...
The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding histocompatibility have advanced significantly in recent years, criteria define DSA assign level risk for given vary markedly between centers. A collaborative effort American Society Histocompatibility Immunogenetics Transplantation provided logistical support generating...
Noninvasive biomarkers are needed to assess immune risk and ultimately guide therapeutic decision-making following kidney transplantation. A requisite step toward these goals is validation of markers that diagnose and/or predict relevant transplant endpoints. The Clinical Trials in Organ Transplantation-01 protocol a multicenter observational study 280 adult pediatric first recipients. We compared validated urinary mRNAs proteins as biopsy-proven acute rejection (AR) stratify patients into...
Despite more than two decades of use, the optimal maintenance dose tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with trough levels and recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort 596 renal 50,011 serial had eplet mismatch using HLAMatchmaker software. analyzed frequency below a series thresholds <6 ng/ml mean before dnDSA in context was...
Alloimmune risk stratification in renal transplantation has lacked the necessary prognostic biomarkers to personalize recipient care or optimize clinical trials. HLA molecular mismatch improves precision compared traditional antigen but not been studied detail at individual molecule level. This study evaluated 664 transplant recipients and correlated HLA-DR/DQ single eplet with serologic, histologic, outcomes. Compared whole mismatch, improved correlation de novo donor-specific antibody...
In renal transplantation, a positive cytotoxic crossmatch between donor cells and recipient serum is associated with early rejection or graft loss was the driving force behind establishment of HLA laboratories. Initially, crossmatches were performed by relatively insensitive techniques [e.g. leukoagglutination direct complement-dependent cytotoxicity (CDC) target cells]. A negative result justified proceeding, while considered contraindication to transplantation.
ABSTRACT. At present, the diagnosis of renal allograft rejection requires a biopsy. Clinical management transplant patients would be improved by development non-invasive markers that can measured frequently. This study sought to determine whether such candidate proteins detected in urine using mass spectrometry. Four patient groups were rigidly defined on basis function, clinical course, and biopsy result: acute group (n = 18), stable 22), tubular necrosis 5), recurrent (or de novo)...
Tissue remodeling depends on mesenchymal cells (fibroblasts and myofibroblasts) is a prominent feature of chronic renal-transplant rejection. It not known whether the that participate in originate locally or from circulating precursor cells.We obtained biopsy specimens renal allografts six male recipients an allograft female donor, four two donor. All were undergoing but within months after transplantation. We used immunohistochemical methods to identify with smooth-muscle alpha-actin situ...
ABSTRACT. Flow cytometric crossmatching (FCXM) and panel reactive antibody (PRA) screening techniques are more sensitive than anti-human globulin enhanced cytotoxicity (AHG-CDC) at detecting anti-HLA antibodies. The clinical significance of a positive FCXM in primary renal transplant recipients with negative AHG-CDC crossmatch is unclear. We performed retrospective flow (FlowPRA) determinations T cell B CDC pretransplant. Eighteen (13%) 143 patients exhibited FCXM. Of these patients, six...
The IL-2 pathway is portrayed often as central to allograft rejection. To test this hypothesis, we studied IL-2-deficient mice recipients. gene knockout (KO) reject islet allografts and demonstrate a classical mononuclear leukocytic infiltrate, containing CD4+ CD8+ T cells, surrounding invading the allografts. Moreover, rejection in KO mouse associated with intragraft expression of certain cytokine CTL attack molecule genes (e.g. IFN-gamma, IL-4, IL-7, IL-10, granzyme B). In separate...