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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

Artikel i vetenskaplig tidskrift
Författare I. Soveri
Johan Mölne
F. Uhlin
T. Nilsson
C. Kjellman
E. Sonesson
M. Segelmark
Publicerad i Kidney International
Volym 96
Nummer/häfte 5
Sidor 1234-1238
ISSN 0085-2538
Publiceringsår 2019
Publicerad vid Institutionen för biomedicin
Sidor 1234-1238
Språk en
Länkar dx.doi.org/10.1016/j.kint.2019.06.0...
Ämnesord anti-GBM disease, IdeS, IgG, PLEX, experimental glomerulonephritis, goodpastures disease, specificity, ides, Urology & Nephrology
Ämneskategorier Urologi och njurmedicin

Sammanfattning

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 antiGBM antibodies. The clinical utility, dosing and usage to preserve renal function remain to be determined.

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