Gluten and IgA nephropathy: you are what you eat? Chee Kay Cheung, Jonathan Barratt  Kidney International  Volume 88, Issue 2, Pages 215-218 (August 2015) DOI: 10.1038/ki.2015.149 Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 1 Potential links between dietary gluten, and IgA nephropathy. (1) Increased intestinal permeability with disruption of epithelial cell tight junctions, possibly due to enhanced antigen sensitivity in IgA nephropathy or other triggers including stress, infection or chemical injury, leads to increased dietary antigen absorption, including gluten peptides, from the gut lumen. Apical to basolateral retrotranscytosis of dietary antigens across the intestinal barrier also takes place in conjunction with secretory IgA. (2) Gliadin, a subcomponent of gluten, then undergoes deamidation by tissue TG2. (3) Deamidated gliadin is taken up by antigen-presenting cells (dendritic cells or macrophages) and interacts with CD4+ T cells. This leads to (4) a TH1 response with production of pro-inflammatory cytokines e.g. TNF-α, IFN-γ, which results in mucosal atrophy, epithelial cell apoptosis and further increase in intestinal permeability and (5) a TH2 response which leads to (6) production of antibodies by B cells residing within mucosa-associated lymphoid tissue (MALT) including IgA and IgG towards gliadin and TG2. (7) Anti-gliadin IgA is released into the circulation and forms immune complexes with soluble CD89 (sCD89) and gliadin. (8) Eventually mesangial deposition of these immune complexes occurs, leading to upregulation of the TF receptor and TG2 expression, amplifying binding of IgA and resulting in mesangial cell activation, cytokine production, and glomerular injury. IFN-γ, interferon-γ; TF, transferrin; TG2, transglutaminase; TNF-α, tumor necrosis factor-α. Kidney International 2015 88, 215-218DOI: (10.1038/ki.2015.149) Copyright © 2015 International Society of Nephrology Terms and Conditions