A Novel Insight into the Role of PLA2R and THSD7A in Membranous Nephropathy

Figure 3

The hypothetical pathogenesis model of PM2.5-associated idiopathic membranous nephropathy (iMN). (a) PM2.5 induces extrarenal anti-PLA2R antibody production. Inhalation of PM2.5 results in the accumulation and activation of alveoli macrophages and neutrophils. PLA2R that is presented on these cells can be discharged into the inflammatory space, when neutrophil extracellular traps (NETs) and macrophage extracellular traps (METs) are released. Inflammation enhances the immunogenicity of the autoantigen and affects the antigen processing capacity of antigen-presenting cells (APCs), which contributes to the autoimmune response. We hypothesize that the PLA2R antigen may be captured by mature APCs, which become accessible producing anti-PLA2R antibodies. (b) The in situ immune complexes are initiated by binding of extrarenal anti-PLA2R antibodies to endogenous PLA2R in the glomeruli. PM2.5 can also cause renal injury and alter renal microenvironment, which may affect the molecular conformation of PLA2R antigen on the podocytes that is necessary for anti-PLA2R antibodies to bind. Abbreviations: GBM: glomerular basement membrane.