Anti-PLA2R Antibodies in Membranous Nephropathy
Kidney Research UK fund a Manchester Research Project on anti-PLA2R antibodies in membranous nephropathy
Prof Brenchley is leading a team to understand how a-PLA2R autoantibodies that target the podocyte, the specialist cell in the glomerulus that controls filtration of the blood, cause proteinuria in membranous nephropathy.
Dr Rachel Lennon, Paediatric Renal Consultant at Manchester Childrens Hospital and Wellcome Trust Clinical Investigator in Faculty of Life Sciences at University of Manchester is using in vitro cell culture techniques to model the behaviour of glomerular podocytes. Dr Edward McKenzie and Dr Tom Jowitt are experts in molecular cloning, protein expression and biophysical biochemistry techniques at the University of Manchester.
We have developed the first quantitative ELISA for a-PLA2R and documented that healthy controls and patients with other immune mediated glomerulopathies are negative. We have shown that levels of a-PLA2R are significantly higher in IMN patients with active disease compared to remission and that patients with a-PLA2R in the upper tertile are at significantly greater risk of experiencing declining renal function within 5 years. A-PLA2R levels can be lowered by immunosuppressive therapy in some patients with resolution of proteinuria.
These strong clinical associations implicate a-PLA2R in the pathology of IMN. However, they do not prove that a-PLA2R are causative, pathogenic mediators of proteinuria. This project seeks to prove that a-PLA2R are pathogenic agents able to modulate podocyte function in vitro. Such evidence may transform management of IMN to focus on reduction and removal of a-PLA2R with the same urgency that autoantibodies to glomerular basement membrane (GBM) are removed in anti-GBM disease. This may improve outcomes for patients with IMN with immediate effect.