Immunosurveillance of Alglucerase Enzyme Therapy for Gaucher Patients: Induction of Humoral Tolerance in Seroconverted Patients After Repeat Administration.

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Presentation transcript:

Immunosurveillance of Alglucerase Enzyme Therapy for Gaucher Patients: Induction of Humoral Tolerance in Seroconverted Patients After Repeat Administration by Mireille Rosenberg, Wytske Kingma, Mary Anne Fitzpatrick, and Susan M. Richards Blood Volume 93(6):2081-2088 March 15, 1999 ©1999 by American Society of Hematology

Time to seroconversion for Gaucher patients treated with alglucerase. Time to seroconversion for Gaucher patients treated with alglucerase. Sera from patients with at least one sample beyond initiation of therapy were analyzed by ELISA and RIP. A patient was considered seroconverted if a positive ELISA result was confirmed by RIP. Mireille Rosenberg et al. Blood 1999;93:2081-2088 ©1999 by American Society of Hematology

Titration of in vitro inhibition of GCR enzymatic activity by sera of seroconverted Gaucher patients. Titration of in vitro inhibition of GCR enzymatic activity by sera of seroconverted Gaucher patients. (A) Representative patient sera showing <50% in vitro inhibitory activity. Transient inhibition was detected when pretreatment, 13, 15, and 18 months posttreatment sera were compared. (B) Patient sera showing >50% inhibition, comparison to normal human serum (NHS) and different time points in therapy. Mireille Rosenberg et al. Blood 1999;93:2081-2088 ©1999 by American Society of Hematology

Time to adverse event for Gaucher patients treated with alglucerase in seroconverted patients (A) and in nonseroconverted patients (B). Time to adverse event for Gaucher patients treated with alglucerase in seroconverted patients (A) and in nonseroconverted patients (B). Mireille Rosenberg et al. Blood 1999;93:2081-2088 ©1999 by American Society of Hematology

ELISA reactivity and tolerization to GCR in six representative seroconverted patients. ELISA reactivity and tolerization to GCR in six representative seroconverted patients. Sera from individual patients were analyzed during their course of therapy by ELISA and RIP. The arrows indicate the time of seroconversion (RIP+) and the time of tolerization (RIP-). A patient was considered seroconverted if a positive ELISA result was confirmed by RIP and tolerized if after seroconversion, both ELISA and RIP of subsequent sera samples were negative. Mireille Rosenberg et al. Blood 1999;93:2081-2088 ©1999 by American Society of Hematology