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.