The IgG-degrading enzyme of Streptococcus pyogenes causes rapid clearance of anti-glomerular basement membrane antibodies in patients with refractory anti-glomerular basement membrane disease
(2019) In Kidney International 96(5). p.1234-1238- Abstract
In anti-glomerular basement membrane (anti-GBM) disease, IgG class autoantibodies induce rapidly progressive glomerulonephritis. Regrettably, many patients are diagnosed at a late stage when even intensive conventional treatment fails to restore renal function The endopeptidase IdeS (Immunoglobulin G degrading enzyme of Streptococcus pyogenes) (imliflidase) rapidly cleaves all human IgG subclasses into F(ab′)2 and Fc fragments. We received permission to treat three patients with refractory anti-GBM nephritis without pulmonary involvement on a compassionate basis. All patients were dialysis-dependent for days or weeks when treated, and all had high levels of circulating anti-GBM despite plasma exchange. A single dose of IdeS... (More)
In anti-glomerular basement membrane (anti-GBM) disease, IgG class autoantibodies induce rapidly progressive glomerulonephritis. Regrettably, many patients are diagnosed at a late stage when even intensive conventional treatment fails to restore renal function The endopeptidase IdeS (Immunoglobulin G degrading enzyme of Streptococcus pyogenes) (imliflidase) rapidly cleaves all human IgG subclasses into F(ab′)2 and Fc fragments. We received permission to treat three patients with refractory anti-GBM nephritis without pulmonary involvement on a compassionate basis. All patients were dialysis-dependent for days or weeks when treated, and all had high levels of circulating anti-GBM despite plasma exchange. A single dose of IdeS led to complete clearance of circulating anti-GBM antibodies in all three patients. After about a week, all rebounded but the rebounds were easily managed by plasma exchange in two of three cases. Renal histology demonstrated severe crescentic glomerulonephritis with acute but mainly chronic changes. Staining for the Fc fragment was negative in all while Fab was positive in two patients. Unfortunately, none of the patients regained independent renal function. Thus, treatment with IdeS led to rapid clearance of circulating and kidney bound anti-GBM antibodies. The clinical utility, dosing and usage to preserve renal function remain to be determined.
(Less)
- author
- Soveri, Inga ; Mölne, Johan ; Uhlin, Fredrik LU ; Nilsson, Thomas ; Kjellman, Christian LU ; Sonesson, Elisabeth and Segelmark, Mårten LU
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- anti-GBM disease, IdeS, IgG, PLEX
- in
- Kidney International
- volume
- 96
- issue
- 5
- pages
- 1234 - 1238
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85072586629
- pmid:31563334
- ISSN
- 0085-2538
- DOI
- 10.1016/j.kint.2019.06.019
- project
- Behandling av anti-GBM glomerulonefrit med ett bakteriellt endopeptidas
- language
- English
- LU publication?
- no
- id
- b91b9c39-b25a-4754-9177-e3cb0d6049ec
- date added to LUP
- 2020-06-15 17:02:59
- date last changed
- 2024-08-07 20:43:42
@article{b91b9c39-b25a-4754-9177-e3cb0d6049ec, abstract = {{<p>In anti-glomerular basement membrane (anti-GBM) disease, IgG class autoantibodies induce rapidly progressive glomerulonephritis. Regrettably, many patients are diagnosed at a late stage when even intensive conventional treatment fails to restore renal function The endopeptidase IdeS (Immunoglobulin G degrading enzyme of Streptococcus pyogenes) (imliflidase) rapidly cleaves all human IgG subclasses into F(ab′)<sub>2</sub> and Fc fragments. We received permission to treat three patients with refractory anti-GBM nephritis without pulmonary involvement on a compassionate basis. All patients were dialysis-dependent for days or weeks when treated, and all had high levels of circulating anti-GBM despite plasma exchange. A single dose of IdeS led to complete clearance of circulating anti-GBM antibodies in all three patients. After about a week, all rebounded but the rebounds were easily managed by plasma exchange in two of three cases. Renal histology demonstrated severe crescentic glomerulonephritis with acute but mainly chronic changes. Staining for the Fc fragment was negative in all while Fab was positive in two patients. Unfortunately, none of the patients regained independent renal function. Thus, treatment with IdeS led to rapid clearance of circulating and kidney bound anti-GBM antibodies. The clinical utility, dosing and usage to preserve renal function remain to be determined.</p>}}, author = {{Soveri, Inga and Mölne, Johan and Uhlin, Fredrik and Nilsson, Thomas and Kjellman, Christian and Sonesson, Elisabeth and Segelmark, Mårten}}, issn = {{0085-2538}}, keywords = {{anti-GBM disease; IdeS; IgG; PLEX}}, language = {{eng}}, number = {{5}}, pages = {{1234--1238}}, publisher = {{Nature Publishing Group}}, series = {{Kidney International}}, title = {{The IgG-degrading enzyme of Streptococcus pyogenes causes rapid clearance of anti-glomerular basement membrane antibodies in patients with refractory anti-glomerular basement membrane disease}}, url = {{http://dx.doi.org/10.1016/j.kint.2019.06.019}}, doi = {{10.1016/j.kint.2019.06.019}}, volume = {{96}}, year = {{2019}}, }