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
Autor: | Christian Kjellman, Thomas Nilsson, Johan Mölne, Mårten Segelmark, Inga Soveri, Fredrik Uhlin, Elisabeth Sonesson |
---|---|
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Anti-Glomerular Basement Membrane Disease 030232 urology & nephrology Renal function urologic and male genital diseases Immunoglobulin G 03 medical and health sciences 0302 clinical medicine Bacterial Proteins medicine Humans Rapidly progressive glomerulonephritis Kidney biology business.industry Glomerular basement membrane medicine.disease Treatment Outcome 030104 developmental biology medicine.anatomical_structure Nephrology Immunology biology.protein Antibody business Nephritis |
Zdroj: | Kidney International. 96:1234-1238 |
ISSN: | 0085-2538 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |