Figure 1.

Three pathways of complement activation in PLA2R-associated MN. The classical pathway is often initiated by IgG1, IgG2, and IgG3. The lectin pathway is normally initiated by bindings of LP-recognition molecules (ie MBL, ficolins) to various carbohydrates or acetylated residues on the surface of pathogens (most commonly mannose residues) and aberrant glycosylated IgG4 of anti-PLA2R antibodies particularly in PLA2R-associated MN. The alternative pathway is spontaneously activated by the hydrolysis of the C3. After factor B (FB) has been activated to Bb by factor D (FD), Bb interacts with C3 (H2O) to form a C3 convertase. C3 convertases cleave C3 into the anaphylatoxin C3a and C3b. C3b deposited on surfaces can form additional C3 convertases (C3bBb), and this drives the C3 amplification loop. Then the downstream complements are activated and lead to the assembly of the membrane attack complex (MAC).