Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies

Gupta, Anjali; Broin, Pilib Ó; Bao, Yi; Pullman, James; Kamal, Layla; Ajaimy, Maria; Lubetzky, Michelle; Colovai, Adriana I.; Schwartz, Daniel S.; Boccardo, Graciela de; Golden, Aaron; Akalin, Enver

doi:10.1038/ki.2015.276

Cited by 53 publications

(44 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All of the biopsies analysed in this study were scored by three different pathologists following the 2013 Banff classification [8]. We excluded all cases that could be subject to alloantibodymediated processes, such as the presence of DSA and microvascular inflammation, even in the absence of C4d positivity [13]. A few cases in our cohort of chronic TCMR presented isolated minimal signs of acute lesions, but chronic lesions predominantly led to a diagnosis of chronic TCMR.…”

Section: Discussionmentioning

confidence: 99%

Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

Curci

Sallustio

Serino

et al. 2016

Nephrol. Dial. Transplant.

View full text Add to dashboard Cite

Background. Chronic T cell-mediated rejection (TCMR) in kidney graft is characterized by reduction of the vessel lumen with marked intimal thickening, fibrous hyperplasia of the small renal arteries and leukocyte infiltrates. The aim of this study was to find specific gene expression profiles in chronic TCMR kidney biopsies. Methods. RNA extracted from archival formalin-fixed, paraffinembedded renal biopsies was used for gene expression profiling. Our study included 14 patients with chronic TCMR and 10 with acute TCMR. Fifty-two cadaveric donors were used as controls. The results were validated in an independent set of kidney biopsies. Results. We identified 616 and 243 differentially expressed genes with a fold change ≥1.5 and a false discovery rate <0.05 in chronic and acute TCMR, respectively. Pathway analysis revealed upregulation of OX40 signalling. This pathway is involved in the generation of CD8 + effector memory T cells and the upregulation of killer cell lectin-like receptor G1 (KLRG-1), B lymphocyte-induced maturation protein 1 (BLIMP-1) and CD25, which characterize CD8 + effector memory T cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

Curci

Sallustio

Serino

et al. 2016

Nephrol. Dial. Transplant.

View full text Add to dashboard Cite

show abstract

“…A set of transcripts (DSA‐specific transcripts [DSASTs]) was determined to be differentially expressed in renal allograft biopsies from DSA‐positive versus ‐negative patients 29, a finding that was later confirmed independently at a different center 30. Consequently, DSASTs have the potential to identify cases of ABMR in patients with non‐detectable HLA DSA.…”

Section: Dsa Against Hla or Other Antigens In The Diagnosis Of Abmrmentioning

confidence: 99%

The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology

Loupy

Haas

Solez

et al. 2017

American Journal of Transplantation

567

581

View full text Add to dashboard Cite

The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d‐negative antibody‐mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor‐specific antibody tests (anti‐HLA and non‐HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i‐IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell–mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus‐based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next‐generation clinical trials.

show abstract

“…These studies have led to the creation of gene lists called pathogenesisbased transcript sets (PBTs), which represent the underlying biology of major events in transplantation, for example, those highly expressed in effector T cells or those induced by IFNγ (see Alberta Transplant Applied Genomics Centre Gene Lists). These PBTs have been specifically developed to aid understanding of renal inflammation and injury in transplantation, and have been used by other laboratories as well as our own 39,63,64 . Other anno tation systems can also be used to map genes onto biolog ical pathways, for example, Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Broad Institute gene sets.…”

Section: Pathogenesis-based Transcript Setsmentioning

confidence: 99%

Molecular assessment of disease states in kidney transplant biopsy samples

2016

View full text Add to dashboard Cite

Progress in renal transplantation requires improved understanding and assessment of rejection and injury. Study of the relationship between gene expression and clinical phenotypes in kidney transplant biopsy samples has led to the development of a system that enables diagnoses of specific disease states on the basis of messenger RNA levels in the biopsy sample. Using this system we have defined the molecular landscape of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), acute kidney injury (AKI), and tubular atrophy and interstitial fibrosis. TCMR and ABMR share IFNγ-mediated effects and TCMR has emerged as a cognate T cell-antigen presenting cell process in the interstitium, whereas ABMR is a natural-killer-cell-mediated process that occurs in the microcirculation. The specific features of these different processes have led to the creation of classifiers to test for TCMR and ABMR, and revealed that ABMR is the principal cause of kidney transplant deterioration. The molecular changes associated with renal injury are often more extensive than suggested by histology and indicate that the progression to graft failure is caused by continuing nephron injury, rather than fibrogenesis. In summary, advances in the molecular assessment of disease states in biopsy samples has improved understanding of specific processes involved in kidney graft outcomes.

show abstract

Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies

Cited by 53 publications

References 17 publications

Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology

Molecular assessment of disease states in kidney transplant biopsy samples

Contact Info

Product

Resources

About