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Journal Club #8: The Role of Epitope Retrieval in the Production of Anti-Glomerular Basement Membrane Antibodies in the Antibody-Associated Vasculitis Model

A recent publication from Yuka Nishibata et al. in the Research Square Journal implicated epitope retrieval in the production of anti-glomerular basement membrane (GBM) antibodies in an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) model, as confirmed by Chondrex, Inc.’s rat anti-α3 chain of the non-collagenous region of type IV collagen (α3(IV)NC1) IgG2a monoclonal antibody (mAb), clone H31.

AAV is a group of diseases characterized by inflammation and destruction of small vessels and serum ANCA. On the other hand, anti-GBM disease is an organ-specific autoimmune disorder. The disease manifests as necrotizing crescentic glomerulonephritis and pulmonary hemorrhage and accompanies the production of anti-GBM antibodies. Approximately 5% of AAV patients have serum anti-GBM antibodies. An AAV model in WKY rats was used to study the role antigen retrieval plays in inducing anti-α3(IV)NC1 antibodies.

Using immunohistochemistry, the anti-α3(IV)NC1 mAb failed to bind to the GBM and the basement membrane of Bowman’s capsules in formalin-fixed, paraffin-embedded normal kidney sections without antigen retrieval. However, the mAb bound to antigens who received heat treatment under acidic conditions, a treatment of proteases from S. griseus or neutrophil elastase, but was not able to bind antigens who received heat treatment under neutral or alkaline conditions. This suggests that ANCA activated neutrophils may digest type IV collagen and expose epitopes such as α3(IV)NC1 which then induce production of anti-GBM antibodies.

For more information, please refer to the following link

Y. Nishibata, M. Nonokawa, Y. Tamura, R. Higashi, K. Suzuki, H. Hayashi, S. Masuda, D. Nakazawa, S. Tanaka, U. Tomaru, et al, Possible Implication of Intermolecular Epitope Spreading in the Production of Anti-Glomerular Basement Membrane Antibody in Anti-Neutrophil Cytoplasmic Antibody-associated Vasculitis. Research Square (2021).

In order to study the contribution of autoantibodies to disease in rat nephritis models, Chondrex, Inc. provides epitope defined monoclonal antibodies against each α chain (IV)NC1, nephritogenic monoclonal antibodies, and nephritogenic NC1 to induce rat glomerulonephritis models, and cationic BSA for mouse nephropathy models. Chondrex, Inc. plans to provide reagents to induce rat and mouse AAV models in the future. 

Please refer to Chondrex, Inc’s website for more information.
Nephritis - Rat Anti-Glomerular Basement Membrane Nephritis Models
Nephritis - Mouse Immune Complex Glomerulonephritis Induced by Cationic BSA
Anti-Collagen Antibodies