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Different dose‐dependent correction of MIP‐1β and chitotriosidase during initial enzyme replacement therapy
Author(s) -
Breemen M. J.,
Fost M.,
Maas M.,
Wiersma M. G.,
Hollak C. E. M.,
Poll L. W.,
Dahl S.,
Boot R. G.,
Aerts J. M. F. G.
Publication year - 2009
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-009-1064-5
Subject(s) - enzyme replacement therapy , glucocerebrosidase , mannose , enzyme , mannose receptor , medicine , endocrinology , biology , pathology , immunology , biochemistry , disease , in vitro , macrophage
Summary In tissue lesions of type I Gaucher patients, characteristic lipid‐laden macrophages, ‘Gaucher cells’, are surrounded by inflammatory phagocytes. Gaucher cells secrete the elevated plasma chitotriosidase. The elevated plasma MIP‐1β in Gaucher patients stems from the phagocytes surrounding the Gaucher cells. Plasma chitotriosidase and MIP‐1β decrease upon successful enzyme replacement therapy (ERT) with mannose‐terminated recombinant glucocerebrosidase (alglucerase). Previous histochemical analysis of Gaucher spleens revealed that Gaucher cells express little mannose receptor, in contrast to surrounding phagocytes. We therefore investigated the corrective effects of ERT on plasma MIP‐1β and chitotriosidase in more detail. We also compared effects of one year of treatment with a relatively low dose and a relatively high dose of ERT. A more rapid correction in plasma MIP‐1β, compared to chitotriosidase, was observed in most patients on low‐dose ERT. Correction of plasma MIP‐1β and chitotriosidase levels was more pronounced in the higher‐dosed patient group. Upon prolonged treatment, differences in the effects of enzyme dose were no longer significant. Normalization of plasma MIP‐1β and chitotriosidase levels was attained in the majority of patients. In conclusion, ERT with mannose‐terminated gluocerebrosidase results in prominent corrections of plasma chitotriosidase, a marker of Gaucher cells, and in particular of plasma MIP‐1β, a marker of inflammatory phagocytes. The sharper response in plasma MIP‐1β to ERT is in line with the observation that especially phagocytes surrounding Gaucher cells express mannose‐receptors.