2013 - International Conference on Transplantomics and Biomarkers in Organ Transplantation


Plenary 3: Chronic Rejection

4.3 - Detecting graft damage

Presenter: Philip, O'Connell, , Australia
Authors: Philip J. O’Connell


Overview:
Detecting Graft Damage
Philip J. O’Connell MB,BS, PhD.
Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney, Westmead Hospital,
Australia

Renal allograft tubulointerstitial damage is characterised by interstitial fibrosis, tubular atrophy, vascular changes and glomerulosclerosis. Multiple immune and non-immune mechanisms have been implicated in its pathogenesis. However, the molecular pathways and signaling networks involved are poorly defined. Whilst there are many potential causes of injury, there are limited biological pathways that result in fibrosis. At present the pathogenesis of renal allograft fibrosis is controversial. In all likelihood the key initiating events change over time and differ between different patient cohorts. Fibrosis is the result of ongoing activation of myofibroblasts, which can be derived from multiple sources. Some studies have identified EMT as an important source. Others have identified myofibroblasts to be of recipient origin. In the context of renal transplantation, early inflammatory events are important in the recruitment of myofibroblasts. Acute cellular rejection and subclinical rejection have been identified as important causes of IF/TA in the first two years of transplantation. In mechanistic studies of fibrosis chemokines such as CCL2 and CCL3 are important for the recruitment of myofibroblasts and Th2 T cell responses induce dysregulated alternatively activated (M2) macrophages that secrete TGFb. This link between inflammation and fibrosis may be an important initiator of fibrosis after transplantation. Gene array studies have been undertaken in several renal transplant cohort studies and show a consistent pattern of gene expression pathways linking immune and fibrotic gene expression profiles. In longitudinal studies gene expression profiles predictive of fibrosis can predate histological evidence and has the potential to be predictive of future damage. Data linking macrophage infiltration and T-cell mediated immune activation with the development of fibrosis will be presented, whilst evidence of EMT in longitudinal cohort studies was largely lacking. Gene expression profiles that are predictive of future fibrosis can be developed as a biomarker assay that is a better predictor than histology or clinical data and has the potential to better define the pathogenesis of the condition.


You must be logged in to view recordings

Important Disclaimer

By viewing the material on this site you understand and accept that:

  1. The opinions and statements expressed on this site reflect the views of the author or authors and do not necessarily reflect those of The Transplantation Society and/or its Sections.
  2. The hosting of material on The Transplantation Society site does not signify endorsement of this material by The Transplantation Society and/or its Sections.
  3. The material is solely for educational purposes for qualified health care professionals.
  4. The Transplantation Society and/or its Sections are not liable for any decision made or action taken based on the information contained in the material on this site.
  5. The information cannot be used as a substitute for professional care.
  6. The information does not represent a standard of care.
  7. No physician-patient relationship is being established.

Our Corporate Sponsors

TTS gratefully acknowledges the Corporate Partners whose generous support makes the work of the Society possible:

  • astellas
  • roche
  • sanofi