Prof Brenchley is developing novel therapeutic approaches for autoimmune disease using anti-PLA2R positive membranous nephropathy as a paradigm

Since 2009, my group has investigated the autoimmune mechanism causing membranous nephropathy, a rare glomerulopathy associated with heavy proteinuria and the most common cause of nephrotic syndrome in adults.

We have

• developed the first ELISA for quantitating circulating anti-PLA2R antibodies in patients
• linked levels of anti-PLA2R with the HLA DQA1 *05:01 DQB1 *02:01 allotype
• studied the role of anti-PLA2R levels in clinical management of patients over time
• identified the dominant epitope on PLA2R as a 31mer disulphide bonded structure
• identified A2t as a coreceptor for PLA2R on podocytes
• proposed a new structure for PLA2R based on single molecule EM
• developed an ELISA for the minor autoantigen THSD7A
• identified a common epitope structure shared by PLA2R and THSD7A
• contributed to the largest global GWAS in MN which confirms DQA1 and PLA2R as risk genes and identifies NfKB and IRF4 as additional risk genes for MN
• contributed to the first study of recurrent MN in transplants which identifies a donor specific HLA-D risk factor
• identified candidate T cell epitopes in PLA2R

Collaborators

In Manchester

• Dr Tom Jowitt, Wellcome Cell Matrix Centre, Univ of Manchester
• Maryline Fresquet, Wellcome Cell Matrix Centre, Univ of Manchester
• Prof Rachel Lennon, Wellcome Cell Matrix Centre, Univ of Manchester
• Dr Edward McKenzie, FLS, Univ of Manchester
• Prof Sandip Mitra, Renal Medicine, MFT
• Dr Durga Kanigicherla, Renal Medicine, MFT
• Dr Patrick Hamilton, Renal Medicine, MFT & Univ of Manchester
• Prof Kay Poulton, Transplantation Labs, MFT
• Dr Steve Roberts, Biostatistics, Univ of Manchester

 In UK

• Prof IanS Roberts, John Radcliffe Infirmary, Oxford
• Prof Robert Kleta, Center for Nephrology, University College, London
• Dr Gavin Welsh, Dept of Nephrology, University of Bristol

International

• Dr Dan Cattran, University of Toronto, Canada
• Dr Fernando Fervenza, Mayo Clinic, Rochester, USA
• Dr Jack Wetzels, Univ of Nijmegen, The Netherlands
• Prof Pierre Ronco, Hopital Tenon, Paris
• Dr Ron Korstanje, Jackson Labs, Bar Harbor, USA

B.Sc. 1971; University of Birmingham

Ph.D. 1975; University of Manchester