Autoimmune kidney diseases: the MASSPROT and BIOINFO platforms contribute to understanding the pathophysiological mechanisms of membranous nephropathy

Picture credit : Astra Zeneca Foundation

Currently, the diagnosis of membranous nephropathy (an auto immune disease of the kidney which targets the glomeruli, the filters of the kidney) relies either on the kidney biopsy and/or the detection of circulating autoantibodies against the receptor to phospholipase A₂ (PLA₂R) in the blood of the patient.

At the de Duve institute, the teams of Prof. Johann Morelle and Dr Didier Vertommen (MASSPROT platform) improved the original technique of proteomic analysis by applying a specific and more sensitive mass spectrometry method (laser capture microdissection and mass spectrometry with data-independent acquisition)¹.

Combined with bioinformatics analysis performed by Prof. Laurent Gatto (Institut de Duve) and his team (BIOINFO platform), this technique was applied on kidney biopsies to identify specific antigens and disease mechanisms.

Using this proteomic analysis, it is possible to analyze and quantify all the peptides and proteins present in the glomeruli of patients, to identify the specific target antigen in each patient with membranous nephropathy.

This technique also allows to identify the molecular mechanisms involved in the disease progression and severity in those patients with membranous nephropathy, and to identify potentially actionable drug targets for future research.
 

Prof. Johann Morelle - "This precise diagnosis will make it possible to tailor
treatment in order to improve its effectiveness while limiting side effects;
to prevent or delay progression to dialysis or the need for a kidney
transplant; and to improve the quality of life of patients suffering
from autoimmune kidney diseases.
This technique also enables us to better understand the mechanisms
of the disease and to identify new therapeutic targets."

The team aims to implement this new tool into clinical practice over the next few years.

Unveiling new pathways and targets may help individualizing therapy and monitoring to each patient and, ultimately, improving outcomes and quality of life for patients with autoimmune kidney diseases.

Find out more in a video on Prof. Johann Morelle’s research

¹Mass Spectrometry With Data-Independent Acquisition for the Identification of Target Antigens in Membranous Nephropathy. J. Morelle, S. Aydin, H. Debiec, N. Demoulin, I. Dufour, M. Martin, L. Gatto, D. Vertommen, P. Ronco. American Journal of Kidney Diseases, 2025, 6, (1), 63-73.e1

doi: 10.1053/j.ajkd.2025.01.014

This research was carried out with the support of the AstraZeneca Foundation and was recognized with an award in 2023.