Figure 1.

An overview of the pathophysiology of IgAN. (a) Infections, inflammation, or disruptions to host mucosal microbiota in conjunction with (b) increased mucosal permeability can lead to (c) mucosal immune cells being activated via toll like receptors. (d) This leads to an in increased production of BAFF and APRIL and (e) activation of mucosal B-cells via T-cell independent mechanisms, although these cells may also be activated by T-cells. (f) Activated B-cells traffic to central lymph nodes and (g) then traffic back to mucosal sites or mis-home to systemic sites such as bone marrow. (h) Mucosally-derived plasma cells produce Gd-IgA1 of which the magnitude is in part determined by genetic and epigenetic factors, which take up (i) polymeric and secretory forms. (j) Gd-IgA1 containing circulating immune complexes (k) deposit in the glomerular mesangium, (l) variably activating inflammatory pathways, including the lectin and alternative pathways of the complement system.

BAFF, B-cell activating factor; Gd-IgA1, galactose deficient-IgA1; IgAN, IgA nephropathy.