| Title: | Possible implication of intermolecular epitope spreading in the production of anti-glomerular basement membrane antibody in anti-neutrophil cytoplasmic antibody-associated vasculitis |
| Authors: | Nishibata, Yuka Browse this author |
| Nonokawa, Mayu Browse this author |
| Tamura, Yuto Browse this author |
| Higashi, Rio Browse this author |
| Suzuki, Ku Browse this author |
| Hayashi, Hideyuki Browse this author |
| Masuda, Sakiko Browse this author →KAKEN DB |
| Nakazawa, Daigo Browse this author →KAKEN DB |
| Tanaka, Satoshi Browse this author →KAKEN DB |
| Tomaru, Utano Browse this author →KAKEN DB |
| Ishizu, Akihiro Browse this author →KAKEN DB |
| Keywords: | anti-neutrophil cytoplasmic antibody (ANCA) |
| ANCA-associated vasculitis |
| anti-glomerular basement membrane antibody |
| intermolecular epitope spreading |
| Issue Date: | 4-May-2022 |
| Publisher: | Clinical and Experimental Rheumatology S.A.S. |
| Journal Title: | Clinical and experimental rheumatology |
| Volume: | 40 |
| Issue: | 4 |
| Start Page: | 691 |
| End Page: | 704 |
| Publisher DOI: | 10.55563/clinexprheumatol/6oq9du |
| PMID: | 35200124 |
| Abstract: | Objective Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is sometimes complicated by anti-glomerular basement membrane (GBM) disease. Proteases, including elastase, released from neutrophils activated by ANCA are implicated in the pathogenesis of AAV. Epitopes of anti-GBM antibody exist in the alpha 3-subunit non-collagenous (NC1) domain of collagen type IV [Col (IV)]. This region, called alpha 3(IV)NC1, is structurally cryptic. This study aimed to determine the production mechanism of anti-GBM antibody in AAV. Methods We first examined whether alpha 3(IV)NC1 could be revealed by the digestion of formalin-fixed, paraffin-embedded (FFPE) normal kidney sections and Col (IV) by proteases, including neutrophil elastase, using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Next, the reveal of alpha 3(IV)NC1 and the infiltration of CD11c(+) macrophages in the affected kidneys were evaluated by IHC and immunofluorescent staining using FFPE sections. Finally, the production of anti-GBM antibody in AAV rats was determined by ELISA. Results alpha 3(IV)NC1 was revealed by the digestion of FFPE normal kidney sections and Col (IV) by proteases. Although the reveal of alpha 3(IV)NC1 was observed in sclerotic glomeruli regardless of causative diseases, CD11c(+) macrophages near alpha 3(IV)NC1 were characteristics of AAV. Anti-GBM antibody was produced subsequent to ANCA in some AAV rats. IHC demonstrated the reveal of alpha 3(IV)NC1 in affected renal tissues and the infiltration of CD11c(+) macrophages around the sites. Conclusion The collective findings suggest that, in AAV, proteases released from neutrophils activated by ANCA digest Col (IV) and result in the reveal of alpha 3(IV)NC1, CD11c(+) macrophages present GBM epitopes, and then the host's immune system produce anti-GBM antibody. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/86248 |
| Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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