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. 2020 Sep 16;11:1846. doi: 10.3389/fimmu.2020.01846

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Copyright © 2020 Liu, Gao, Liu, Dai, Feng, Dong, Zheng, Gao, Tian and Liu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Relationship between extrarenal tissue, immune response, and glomerular damage. Auto-antigens exposure in inflammatory environment induce the auto-immune response, and subsequently immunoglobulins (Ig) undergo class switching. IgG1 mediates the most auto-antigen clearance as the primary effector antibody, and IgG4 blocks auto-antigens as the high affinity anti-inflammatory antibody. When pathogens and auto-antigens are effectively eliminated, the extrarenal inflammatory, and immune responses tend to be alleviated. However, large amounts of antibodies are deposited in the glomeruli, especially IgG4, leading to filtration barrier damage and proteinuria. Extrarenal remission and glomerular damage aggravation were observed, which can be the reason that why idiopathic membranous nephropathy is having trouble finding the primary foci.