Effect of enzyme replacement therapy on gammopathies in Gaucher disease

Abstract

Chronic antigenic stimulation by the abnormal lipid storage has been postulated to be the mechanism underlying anecdotal reports of monoclonal and polyclonal gammopathies as well as an increased incidence of multiple myeloma in patients with Gaucher disease of all ages. With the advent of specific enzyme therapy, it has been possible to ascertain whether signs and symptoms associated with Gaucher disease are true features of the disorder by virtue of their responsiveness to treatment. The purpose of this study was to assess the incidence of polyclonal and monoclonal gammopathies in a large cohort of patients and the effect of enzyme treatment. All adult patients whose records of immunoglobulin levels were available at presentation or at the advent of enzyme replacement therapy (ERT), and who had been followed for 2 years or receiving ERT for at least 2 years, respectively, and for whom there were also immunoglobulin levels at their most recent follow-up, were included in the study. The incidence of polyclonal gammopathies ranged between 14% and 25% among treated and untreated patients. There were statistically significant percentage decreases per year of enzyme therapy in polyclonal but not monoclonal (1% of all patients) gammopathies. Among enzyme-treated patients, there was no statistically significant difference among patients with regard to spleen status or relative to other parameters of disease severity, hepatitis status, age or gender. This study represents the largest database of gammopathies among patients with Gaucher disease from a large referral clinic. Because there was no correlation of abnormal immunoglobulin levels with disease severity, etiology may not be related to lipid accumulation per se but perhaps reflects a secondary, enzyme-sensitive process, whereas monoclonal gammopathies remain unaffected.