PEDIATRICS Vol. 100 No. 6 December 1997, p. e11

ELECTRONIC ARTICLE:
Management of Neutralizing Antibody to Ceredase in a Patient With Type 3 Gaucher Disease

Received Jan 13, 1997; accepted Aug 19, 1997.

Roscoe O. Brady^*, Gary J. Murray^*, Katherine L. Oliver^*, Susan F. Leitman, Michael C. Sneller^§, Thomas A. Fleisher, Norman W. Barton^*, and Collaborators

From the ^* Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke;  Department of Transfusion Medicine, Clinical Center; ^§ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases;  Clinical Pathology Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.

Objectives.  The beneficial effects of macrophage-targeted glucocerebrosidase (Ceredase) in patients with Gaucher disease are well established. A minority of recipients develop transient nonneutralizing antibodies to the exogenous enzyme. A 7-year-old patient with type 3 Gaucher disease whose clinical course began to deteriorate while receiving Ceredase developed a progressively increasing titer of IgG antibody that blocked the catalytic activity of Ceredase. We sought to develop a strategy that would restore the benefit of enzyme replacement therapy in this patient.

Methods.  The patient was treated with two courses of a combination of plasma exchange, cyclophosphamide, intravenous IgG, and large doses of Ceredase.

Results.  After the second course of this regimen, the titer of the neutralizing antibody in the blood gradually declined to negligible levels. Clinical parameters that had been deteriorating (reduction of hemoglobin level, increased serum acid phosphates activity, repeated skeletal infarctions, progressive enlargement and infarction of the spleen) all improved. There has been no recurrence of the neutralizing antibody in this patient.

Conclusions.  Very few patients with Gaucher disease who are treated with Ceredase develop a neutralizing antibody to the exogenous enzyme. In the rare instances where this phenomenon occurs, it is likely that the strategy we have used (plasma exchange, cyclophosphamide, intravenous IgG, and large doses of enzyme) may provide benefit to such individuals. It is also likely that this technique may be helpful when enzyme replacement therapy is attempted in patients with other disorders in which the genetic mutation abrogates the production of the protein (CRIM-negative individuals).

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