Journal of Inherited Metabolic Disease

, Volume 32, Issue 2, pp 274–279 | Cite as

Different dose-dependent correction of MIP-1β and chitotriosidase during initial enzyme replacement therapy

  • M. J. van Breemen
  • M. de Fost
  • M. Maas
  • M. G. Wiersma
  • C. E. M. Hollak
  • L. W. Poll
  • S. vom Dahl
  • R. G. Boot
  • J. M. F. G. Aerts
Original Article

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.

Abbreviations

AMC

Academic Medical Center, Amsterdam

ERT

enzyme replacement therapy

HHU

Hospital of the Heinrich Heine University, Düsseldorf

MIP-1β

macrophage inflammatory protein 1β

SSI

Severity Score Index

References

  1. Aerts JM, Hollak CE (1997) Plasma and metabolic abnormalities in Gaucher’s disease. Baillières Clin Haematol 10(4): 691–709. doi:10.1016/S0950-3536(97)80034-0.PubMedCrossRefGoogle Scholar
  2. Aerts JM, van Breemen MJ, Bussink AP, et al (2008) Biomarkers for lysosomal storage disorders: identification and application as exemplified by chitotriosidase in Gaucher disease. Acta Paediatr Supplement 97(s457): 7–14. doi:10.1111/j.1651-2227.2007.00641.x.CrossRefGoogle Scholar
  3. Barton NW, Brady RO, Dambrosia JM, et al (1991) Replacement therapy for inherited enzyme deficiency—macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med 324(21): 1464–1470.PubMedGoogle Scholar
  4. Beutler E, Grabowski GA (1995) Gaucher disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 2641–2670.Google Scholar
  5. Boot RG, Hollak CE, Verhoek M, et al (1997) Glucocerebrosidase genotype of Gaucher patients in the Netherlands: limitations in prognostic value. Hum Mutat 10(5): 348–358. doi:10.1002/(SICI)1098-1004(1997)10:5<348::AID-HUMU3>3.0.CO;2-B.PubMedCrossRefGoogle Scholar
  6. Boot RG, Renkema GH,Verhoek M, et al (1998) The human chitotriosidase gene: nature of inherited enzyme deficiency. J Biol Chem 273(40): 25680–25685. doi:10.1074/jbc.273.40.25680.PubMedCrossRefGoogle Scholar
  7. Boot RG, Verhoek M, de Fost M, et al (2004) Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention. Blood 103(1): 33–39. doi:10.1182/blood-2003-05-1612.PubMedCrossRefGoogle Scholar
  8. Boven LA, van Meurs M, Boot RG, et al (2004) Gaucher cells demonstrate a distinct macrophage phenotype and resemble alternatively activated macrophages. Am J Clin Pathol 122(3): 359–369. doi:10.1309/BG5VA8JRDQH1M7HN.PubMedCrossRefGoogle Scholar
  9. de Fost M, Hollak CE, Groener JE, et al (2006) Superior effects of high-dose enzyme replacement therapy in type 1 Gaucher disease on bone marrow involvement and chitotriosidase levels: a 2-center retrospective analysis. Blood 108(3): 830–835. doi:10.1182/blood-2005-12-5072.PubMedCrossRefGoogle Scholar
  10. Grabowski GA, Barton NW, Pastores G, et al (1995) Enzyme therapy in type I Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med 122(1): 33–39.PubMedGoogle Scholar
  11. Hollak CE, van Weely S, van Oers MH, Aerts JM (1994) Marked elevation of plasma chitotriosidase activity: a novel hallmark of Gaucher disease. J Clin Invest 93(3): 1288–1292. doi:10.1172/JCI117084.PubMedCrossRefGoogle Scholar
  12. Hollak CE, Aerts JM, Goudsmit R, et al (1995) Individualised low-dose alglucerase therapy for type 1 Gaucher’s disease. Lancet 345(8963): 1474–1478. doi:10.1016/S0140-6736(95)91037-9.PubMedCrossRefGoogle Scholar
  13. Hollak CE, Evers L, Aerts JM, van Oers MH (1997) Elevated levels of M-CSF, sCD14 and IL8 in type 1 Gaucher disease. Blood Cells Mol Dis 23(2): 201–212. doi:10.1006/bcmd.1997.0137.PubMedCrossRefGoogle Scholar
  14. Michelakakis H, Spanou C, Kondyli A, et al (1996) Plasma tumor necrosis factor-a (TNF-a) levels in Gaucher disease. Biochim Biophys Acta 1317(3): 219–222.PubMedGoogle Scholar
  15. Mistry PK, Wraight EP, Cox TM (1996) Therapeutic delivery of proteins to macrophages: implications for treatment of Gaucher’s disease. Lancet 348(9041): 1555–1559. doi:10.1016/S0140-6736(96)04451-0.PubMedCrossRefGoogle Scholar
  16. Schoonhoven A, Rudensky B, Elstein D, et al (2007) Monitoring of Gaucher patients with a novel chitotriosidase assay. Clin Chim Acta 381(2): 136–139. doi:10.1016/j.cca.2007.02.042.PubMedCrossRefGoogle Scholar
  17. van Breemen MJ, de Fost M, Voerman JS, et al (2007) Increased plasma macrophage inflammatory protein (MIP)-1α and MIP-1β levels in type 1 Gaucher disease. Biochim Biophys Acta 1772(7): 788–796.PubMedGoogle Scholar
  18. van Weely S, van Leeuwen MB, Jansen ID, et al (1991) Clinical phenotype of Gaucher disease in relation to properties of mutant glucocerebrosidase in cultured fibroblasts. Biochim Biophys Acta 1096(4): 301–311.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • M. J. van Breemen
    • 1
  • M. de Fost
    • 2
  • M. Maas
    • 3
  • M. G. Wiersma
    • 2
  • C. E. M. Hollak
    • 2
  • L. W. Poll
    • 4
  • S. vom Dahl
    • 5
  • R. G. Boot
    • 1
  • J. M. F. G. Aerts
    • 1
  1. 1.Department of Medical Biochemistry, K1–262University of Amsterdam, Academic Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Endocrinology and MetabolismAcademic Medical CenterAmsterdamThe Netherlands
  3. 3.Department of RadiologyAcademic Medical CenterAmsterdamThe Netherlands
  4. 4.Institute of RadiologyHeinrich-Heine UniversityDuisburgGermany
  5. 5.Clinic for Internal Medicine, University HospitalHeinrich-Heine UniversityCologneGermany

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