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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

Soveri, Inga ; Mölne, Johan ; Uhlin, Fredrik LU ; Nilsson, Thomas ; Kjellman, Christian LU ; Sonesson, Elisabeth and Segelmark, Mårten LU (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.

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author
publishing date
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
  • pmid:31563334
  • scopus:85072586629
ISSN
0085-2538
DOI
10.1016/j.kint.2019.06.019
language
English
LU publication?
no
id
b91b9c39-b25a-4754-9177-e3cb0d6049ec
date added to LUP
2020-06-15 17:02:59
date last changed
2020-07-08 05:17:10
@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},
  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},
}