Volume 66, Issue 4, Pages (October 2004)

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Date of download: 7/14/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Clinical Relevance of Different IgG and IgM Serum.

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Volume 66, Issue 4, Pages 1589-1595 (October 2004) Enzyme therapy for Fabry disease: Neutralizing antibodies toward agalsidase alpha and beta Gabor E. Linthorst, Carla E.M. Hollak, Wilma E. Donker-Koopman, Anneke Strijland, Johannes M.F.G. Aerts Kidney International Volume 66, Issue 4, Pages 1589-1595 (October 2004) DOI: 10.1111/j.1523-1755.2004.00924.x Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 1 Anti-agalsidase IgG titer in patients treated with agalsidase alpha or beta. Open bars represent titer to agalsidase beta, closed bars to agalsidase alpha (normal <1:16). Kidney International 2004 66, 1589-1595DOI: (10.1111/j.1523-1755.2004.00924.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 2 Neutralization of enzyme activity and cross-reactivity of serum incubated with agalsidase alpha (dotted line) or agalsidase beta (solid line), respectively. Kidney International 2004 66, 1589-1595DOI: (10.1111/j.1523-1755.2004.00924.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 3 Demonstration of circulating immune complexes in an IgG-positive patient during an infusion with agalsidase beta in samples taken as part of a pharmacokinetic profile. Before the development of antibodies there is no difference in enzymatic activity in the supernatant of plasma treated with either Sepharose prot A or 4B (A). However, after the development of antibodies enzymatic activity in supernatant is greatly reduced when plasma is incubated with Sepharose prot A, but not with Sepharose 4B, indicating that the majority of circulating enzyme is bound to IgG (B). Kidney International 2004 66, 1589-1595DOI: (10.1111/j.1523-1755.2004.00924.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 4 Enzyme activity in plasma (A) and leukocytes (B) of three IgG-negative (dotted line) and one IgG-positive (solid line) patient after 60 and 120 minutes of in vitro incubation with agalsidase beta. Kidney International 2004 66, 1589-1595DOI: (10.1111/j.1523-1755.2004.00924.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 5 Urinary CTH in both IgG-positive and IgG-negative patients before and after 6 months of treatment with rh-αGal A (A). Results expressed as mean ± SD. *P < 0.01. Urinary CTH in two patients without, and four patients with IgG antibodies during a 12-month treatment period, demonstrating persistent urinary CTH clearance in two IgG-negative patients, where no clearance is seen in IgG-positive patients (B). Results expressed as mean ± SD. Kidney International 2004 66, 1589-1595DOI: (10.1111/j.1523-1755.2004.00924.x) Copyright © 2004 International Society of Nephrology Terms and Conditions