title: Increased plasma macrophage inflammatory protein (MIP)-1alpha and MIP-1beta levels in type 1 Gaucher disease.
abstract: Pancytopenia, hepatosplenomegaly and skeletal complications are hallmarks of Gaucher disease. Monitoring of the outcome of therapy on skeletal status of Gaucher patients is problematic since currently available imaging techniques are expensive and not widely accessible. The availability of a blood test that relates to skeletal manifestations would be very valuable. We here report that macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, both implicated in skeletal complications in multiple myeloma (MM), are significantly elevated in plasma of Gaucher patients. Plasma MIP-1alpha of patients (median 78 pg/ml, range 21-550 pg/ml, n=48) is elevated (normal median 9 pg/ml, range 0-208 pg/ml, n=39). Plasma MIP-1beta of patients (median 201 pg/ml, range 59-647 pg/ml, n=49) is even more pronouncedly increased (normal median 17 pg/ml, range 1-41 pg/ml, n=39; one outlier: 122 pg/ml). The increase in plasma MIP-1beta levels of Gaucher patients is associated with skeletal disease. The plasma levels of both chemokines decrease upon effective therapy. Lack of reduction of plasma MIP-1beta below 85 pg/ml during 5 years of therapy was observed in patients with ongoing skeletal disease. In conclusion, MIP-1alpha and MIP-1beta are elevated in plasma of Gaucher patients and remaining high levels of MIP-1beta during therapy seem associated with ongoing skeletal disease.
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105AZ, Amsterdam, The Netherlands.
authors.forename: Mariëlle J
authors.initials: MJ
authors.lastname: van Breemen
authors.forename: Maaike
authors.initials: M
authors.lastname: de Fost
authors.forename: Jane S A
authors.initials: JS
authors.lastname: Voerman
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Boot
authors.forename: Mario
authors.initials: M
authors.lastname: Maas
authors.forename: Carla E M
authors.initials: CE
authors.lastname: Hollak
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Aerts
authors.forename: Farhad
authors.initials: F
authors.lastname: Rezaee
mesh_terms: D000328:Adult; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005776:Gaucher Disease / Q000097:blood* / Q000628:therapy; D006596:Hexosaminidases / Q000097:blood; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013154:Spleen / Q000378:metabolism
chemical_list: C111792:CCL18 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D006596:Hexosaminidases; C086400:chitotriosidase