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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Soc+Nephrol
2014 ; 25
(4
): 675-80
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gab.com Text
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Allo-immune membranous nephropathy and recombinant aryl sulfatase replacement
therapy: a need for tolerance induction therapy
#MMPMID24262793
Debiec H
; Valayannopoulos V
; Boyer O
; Nöel LH
; Callard P
; Sarda H
; de Lonlay P
; Niaudet P
; Ronco P
J Am Soc Nephrol
2014[Apr]; 25
(4
): 675-80
PMID24262793
show ga
Nephrotic syndrome was reported in a highly-sensitized patient receiving enzyme
replacement therapy (ERT) for Pompe disease, but the prevalence of ERT-induced
renal complications and mechanisms to facilitate readministration of ERT in these
patients remain unexplored. This work identifies a new antigen responsible for
secondary membranous nephropathy (MN) in a patient with mucopolysaccharidosis
type VI caused by aryl sulfatase B (ASB) deficiency. ERT (recombinant human ASB
[rhASB]; 1 mg/kg per week) started at the age of 4 years led to a high anti-rhASB
titer and dramatically improved clinical manifestations. However, 16 months
later, the patient suddenly developed nephrotic syndrome resistant to steroid
therapy 1 week after orthopedic surgery. Examination of the kidney biopsy
specimen revealed glomerular deposition of IgG (mostly IgG4, C3, and C5b-9) in a
granular pattern typical of MN. Double immunofluorescence staining showed that
subepithelial granular deposits contained rhASB colocalized with IgG. Ig eluted
from the patient's biopsy specimen reacted specifically with rhASB. On
discontinuation of ERT, proteinuria progressively decreased, but the patient's
clinical condition markedly deteriorated. Induction of tolerance to rhASB was
initiated by coadministration of low-dose corticosteroids, rituximab, intravenous
Igs, and oral methotrexate. ERT was resumed 8 weeks after starting
immunosuppressive therapy without inducing a rebound of antibody titer or an
increase in proteinuria. We conclude that the allo-immune response to the
recombinant rhASB caused the nephropathy. Considering the critical requirement
for ERT in patients with such enzyme deficiencies, immune tolerance induction
should be advocated in the patients with allo-immune MN.