Metabolic Drivers of Autoimmunity in Membranous Nephropathy

Membranous nephropathy is driven by autoantibody formation against podocyte antigens such as PLA2R, THSD7A, and several less common targets. Beyond antibody specificity, the metabolic state of immune cells shapes how the disease starts, progresses, and responds to therapy.

B cells
Autoreactive B cells survive and expand because they rely heavily on glycolysis, fatty acid oxidation, and glutaminolysis. High BAFF levels strengthen these pathways and support long lived plasma cells that continue producing pathogenic IgG.

T cells
MN shows an elevated Th17 response and weakened Treg activity. This imbalance reflects increased glycolysis, altered mitochondrial function, and shifts in glutamine and pentose phosphate pathways. These changes amplify cytokine driven inflammation and support ongoing B cell activation.

Antigen presenting cells
Dendritic cells and macrophages adjust metabolism during activation. Increased glycolysis and ROS production enhance antigen presentation and inflammation. Although less studied in MN, these shifts likely sustain autoreactive responses within the kidney.

Therapeutic relevance
Many current agents already affect immunometabolism. CNIs restrain glycolysis. MMF limits glutamine use. Proteasome inhibitors disrupt both glycolysis and OXPHOS in plasma cells. SGLT2 inhibitors influence inflammatory signaling and T cell nutrient sensing. As the field advances, metabolism based targeting may help suppress autoreactive clones with greater specificity.

Metabolomics as a tool
Urine and serum metabolites linked to amino acid, lipid, and NAD pathways correlate with disease severity. These signatures may support diagnosis, risk assessment, and treatment monitoring, especially in PLA2R associated disease.

Full Abstract

Are you a healthcare professional? Register with us today!