Once IgA binds to the mesangium, it may stimulate mesangial cell proliferation and trigger mesangial cell release of proinflammatory mediators, such as interleukin 6 and TNF-α, as well as profibrogenic mediators, such as PDGF-β and TGF-β. In addition, IgA appears to activate complement via the alternate pathway and the mannose-binding lectin (MBL) pathway. In normal circumstances, MBL activates complement when its carbohydrate recognition domain (CRD) binds to mannose residues on pathogen surfaces. In IgAN, it is possible that the CRD recognizes the abnormally glycosylated region of the IgA molecule itself. Finally, IgG may target regions of the IgA molecule and promote further inflammation.

Not all IgA that binds to the mesangium, however, is capable of generating disease. In fact, in some series up to 5% to 15% of otherwise healthy individuals are found to have glomerular IgA deposition. The specific changes in IgA that allow it to provoke inflammation after mesangial deposition, as well as the genetic features that underpin these changes, have not been identified.