Expression of B Cell and Immunoglobulin Transcripts Is a Feature of Inflammation in Late Allografts

Einecke, G.; Reeve, J.; Mengel, Michael; Sis, B.; Bunnag, Sakarn; Mueller, Thomas; Halloran, Philip F.

doi:10.1111/j.1600-6143.2008.02232.x

Cited by 88 publications

(90 citation statements)

References 37 publications

(78 reference statements)

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“…(5). The molecular phenotype is reviewed in a companion paper (6) but the lessons from the molecular studies are incorporated here to propose an integrated approach to interpreting biopsy findings and outcomes, (13), mast cell transcripts (14) and FOXP3 mRNA (15). (22).…”

Section: Much Has Changed Since 2002 the Term Chronic Allograft Nephmentioning

confidence: 99%

An Integrated View of Molecular Changes, Histopathology and Outcomes in Kidney Transplants

Halloran

Freitas

Einecke

et al. 2010

American Journal of Transplantation

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Data-driven approaches to deteriorating kidney transplants, incorporating histologic, molecular and HLA antibody findings, have created a new understanding of transplant pathology and why transplants fail. Transplant dysfunction is best understood in terms of three elements: diseases, the active injury-repair response and the cumulative burden of injury. Progression to failure is mainly attributable to antibody-mediated rejection, nonadherence and glomerular disease. Antibodymediated rejection usually develops late due to de novo HLA antibodies, particularly anti-class II, and is often C4d negative. Pure treated T cell-mediated rejection does not predispose to graft loss because it responds well, even with endothelialitis, but it may indicate nonadherence. The cumulative burden of injury results in atrophy-fibrosis (nephron loss), arterial fibrous intimal thickening and arteriolar hyalinosis, but these are not progressive without ongoing disease/injury, and do not explain progression. Calcineurin inhibitor toxicity has been overestimated because burden-of-injury lesions invite this default diagnosis when diseases such as antibody-mediated rejection are missed. Disease/injury triggers a stereotyped active injury-repair response, including dedifferentiation, cell cycling and apoptosis. The active injury-repair response is the strongest correlate of organ function and future progression to failure, but should always prompt a search for the initiating injury or disease.

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Section: Much Has Changed Since 2002 the Term Chronic Allograft Nephmentioning

confidence: 99%

An Integrated View of Molecular Changes, Histopathology and Outcomes in Kidney Transplants

Halloran

Freitas

Einecke

et al. 2010

American Journal of Transplantation

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“…(15,(26)(27)(28)(29)(30). Both protocol and indication biopsies beyond 6 months posttransplant often manifest an increase in B-cell nodules as well as scarring (15,22,26,28 g. IL4, IL6, IL13), potentially through collagen production and fibroblast proliferation (10,33,34 …”

Section: Infiltrates and Scarringmentioning

confidence: 99%

Molecular Correlates of Scarring in Kidney Transplants: The Emergence of Mast Cell Transcripts

Mengel

Reeve

Bunnag

et al. 2009

American Journal of Transplantation

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In the Banff consensus, infiltrates in areas of scarring are ignored. This study aimed to characterize the molecular correlates and clinical significance of scarring and inflammation in scarred areas.We assessed the extent of interstitial infiltrates, tubulitis and scarring in 129 clinically indicated renal allograft biopsies, and correlated the results with microarray expression data and allograft survival. Findings were validated in 50 additional biopsies.Transplants with scarring had a worse prognosis if the scarred area showed infiltrates. Infiltration in unscarred and scarred areas was associated with reduced death censored graft survival. In microarray analysis, infiltration in unscarred areas strongly (>r ± 0.4) correlated with 484 transcripts associated with cytotoxic T cells, interferon-gamma, macrophages and injury. Scarring correlated with a distinct set of 172 transcripts associated with B cells, plasma cells, and others of unknown significance. The strongest correlation was with four mast cell transcripts. In biopsies with scarring, high expression of mast cell transcripts was associated with reduced graft survival and poor functional recovery.In renal allograft biopsies, infiltrates in scarred areas have implications for poor outcomes. Scarring is associated with a distinct pattern of inflammatory molecules, including B cell/immunoglobulin but particularly mast cell-associated transcripts, which correlated with poor outcomes.

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“…We previously reported that fibrosis in human kidney transplants was associated with transcripts expressed in certain inflammatory cells: mast cell transcripts (MCATs) such as carboxypeptidase 3 (CPA3) (26) and immunoglobulin transcripts (IGTs) representing plasma cells (27). Such transcripts do not correlate with TCMR or ABMR.…”

Section: Funding Canada Foundation For Innovation and Genome Canadamentioning

confidence: 99%

Relationships among injury, fibrosis, and time in human kidney transplants

et al. 2016

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Expression of B Cell and Immunoglobulin Transcripts Is a Feature of Inflammation in Late Allografts

Cited by 88 publications

References 37 publications

An Integrated View of Molecular Changes, Histopathology and Outcomes in Kidney Transplants

An Integrated View of Molecular Changes, Histopathology and Outcomes in Kidney Transplants

Molecular Correlates of Scarring in Kidney Transplants: The Emergence of Mast Cell Transcripts

Relationships among injury, fibrosis, and time in human kidney transplants

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