title: Iron homeostasis and infIammatory biomarker analysis in patients with type 1 Gaucher disease.
abstract: Gaucher disease induces some metabolic abnormalities so increased serum ferritin appears in more than 60% at diagnosis. The storage of glucosylceramide in macrophages produces an inflammatory response with iron recycling deregulation and release of cytokines. Iron homeostasis is controlled by the circulating peptide hepcidin and its production is influenced by inflammatory cytokines. Iron damages cells by excess of catalyzing reactive oxygen species, removal of the excess iron has a positive influence on the response to treatment and survival in patients with iron overload. We have analyzed some inflammatory biomarkers of macrophage activation and related to the iron profile, including hepcidin and liver iron deposits determined by MRI, in 8 type 1 GD patients with hyperferritinemia. We have explored the changes in this profile after 4 months under therapy with two different iron chelators, deferoxamine or deferasirox, by evaluating response, adverse events and quality of life. We observed a significant reduction in serum ferritin and hepcidin levels and in liver iron deposits. No differences were observed in chitotriosidase activity, CCL18/PARC concentration and IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1α, MIP-1β,TNF-α cytokine levels. After two years on follow-up, clinical and analytical data were improved and stable ferritin levels maintained less than 700 ng/dL.
authors.affiliation: Translational Research Unit, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain; Instituto Aragonés de Ciencias de la Salud (IACS), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Medrano-Engay
authors.affiliation: Instituto Aragonés de Ciencias de la Salud (IACS), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Zaragoza, Spain; Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Irun
authors.affiliation: Translational Research Unit, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain; Instituto Aragonés de Ciencias de la Salud (IACS), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Zaragoza, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Gervas-Arruga
authors.affiliation: Instituto Aragonés de Ciencias de la Salud (IACS), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain; Hematology Department, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain; Translational Research Unit-Río Hortega Grant, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Andrade-Campos
authors.affiliation: Translational Research Unit, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain; Instituto Aragonés de Ciencias de la Salud (IACS), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Andreu
authors.affiliation: Translational Research Unit, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain; Instituto Aragonés de Ciencias de la Salud (IACS), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Zaragoza, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Alfonso
authors.affiliation: Instituto Aragonés de Ciencias de la Salud (IACS), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Zaragoza, Spain; Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pocovi
authors.affiliation: Translational Research Unit, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain; Instituto Aragonés de Ciencias de la Salud (IACS), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Zaragoza, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Giraldo
mesh_terms: D000328:Adult; D000368:Aged; D001565:Benzoates / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D000077588:Deferasirox; D003676:Deferoxamine / Q000627:therapeutic use*; D005260:Female; D005293:Ferritins / Q000097:blood; D005500:Follow-Up Studies; D005776:Gaucher Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D064451:Hepcidins / Q000097:blood; D006596:Hexosaminidases / Q000097:blood; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D015415:Biomarkers; D016207:Cytokines; C578702:HAMP protein, human; D064451:Hepcidins; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D007501:Iron; D006596:Hexosaminidases; C086400:chitotriosidase; D003676:Deferoxamine; D000077588:Deferasirox
keywords: Chelator; Hepcidine; Inflammatory cytokines; Iron overload; Type 1 Gaucher disease