Rôle des auto-anticorps contre le fragment LG3 du perlecan dans l'insulte vasculaire lors du rejet de l'allogreffe rénale

 

Héloise Cardinal

Centre de recherche du CHUM

 

Domaine : maladies infectieuses et immunitaires

Programme chercheurs-boursiers cliniciens - Junior 1

Concours 2014-2015

For patients who suffer from kidney failure, renal transplantation is the best treatment. However, at times, the graft undergoes rejection. This rejection is more severe and harder to treat when the graft blood vessels are affected. At present time, the involvement of graft vessels can only be diagnosed with a biopsy.

A graft biopsy exposes patients to a risk of bleeding, is costly, and necessitates a short hospital stay. It would thus be useful to measure certain markers in the blood of patients to diagnose or follow-up vessel injury in case of rejection. When the graft circulation is involved, the cells that line up the interior part of the vessels die and release membrane vesicles and other proteins such as LG3, which accelerate vascular injury in animal models directly or through the production of anti-LG3 antibodies. We now wish to assess whether membrane vesicles are elevated in the blood of patients who have kidney graft rejection affecting the vessels and whether their level is associated with poor kidney graft function 1 year after the rejection episode.

In patients with rejection, we want to assess if, and under what circumstances, anti-LG3 antibodies are associated with poor graft outcome. We will also evaluate whether pre-transplant anti-LG3 measurement could help predict which patients are at increased risk of having rejection affecting the vessels. To this end, we will measure membrane vesicles, LG3 and anti-LG3 in the plasma of kidney transplant recipients who participated in the University of Montreal and University of Manitoba Renal Transplant Biobanks since 1999 and correlate their levels with clinical outcomes.