title: Trace element and cytokine concentrations in patients with Fibrodysplasia Ossificans Progressiva (FOP): A case control study.
abstract: Fibrodysplasia Ossificans Progressiva (FOP) is a rare inherited disease characterized by progressive heterotopic ossification. Disease onset, severity and symptoms vary between FOP patients, as does the frequency and activity of so-called flare-ups, during which tendons, ligaments, muscle and soft tissue are replaced by bone. Traumata, infections or other stressors are known inducers of flare-ups, and the hormone Activin A may be involved in disease activity; however, reliable biomarkers for FOP activity are missing, and the basal trace element and inflammatory state of patients are unknown. We hypothesized that FOP patients develop characteristic deficiencies in inflammation-related trace elements and display a chronically increased inflammatory cytokine level, collectively aggravating disease course and flare-up risk. Serum samples from 15 FOP patients and 25 relatives were collected under highest quality standards. Concentrations of Cu, Se and Zn were determined by total reflection X-ray fluorescence, and 27 cytokines along with Activin A by specific antibody-based techniques. Data were tested for normal distribution and analyzed by parametric or non-parametric tests. Concentrations of Se and Cu were not different between the groups, while Zn levels were slightly higher in FOP as compared to controls (1110±251 vs. 970±176ng/ml, P=0.04). The average concentrations of cytokines and Activin A were not different. When focusing on the two patients with self-reported flare-ups, again no obvious differences were noted. The cytokines Eotaxin, G-CSF, hbFGF and TNF-α were within the upper half of measured concentrations, and may warrant further longitudinal analyses. Our data do not support the hypothesis that FOP patients display a characteristic pattern of trace elements or have a generally increased tone of pro-inflammatory cytokines.
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Germany. Electronic address: Laura.hildebrand@charite.de.
authors.forename: Laura
authors.initials: L
authors.lastname: Hildebrand
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Germany. Electronic address: timo.gaber@charite.de.
authors.forename: Timo
authors.initials: T
authors.lastname: Gaber
authors.affiliation: Institute for Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Germany. Electronic address: peter.kuehnen@charite.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Kühnen
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Garmisch-Partenkirchen Medical Center, Garmisch-Partenkirchen, Germany. Electronic address: rmorhart@web.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Morhart
authors.affiliation: Orthopaedic Practice, Bergisch Gladbach, Germany. Electronic address: h.unterboersch@t-online.de.
authors.forename: Heinz
authors.initials: H
authors.lastname: Unterbörsch
authors.affiliation: Institute for Experimental Endocrinology, Charité - Universitätsmedizin Berlin, Germany. Electronic address: lutz.schomburg@charite.de.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Germany. Electronic address: petra.seemann@charite.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Seemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009221:Myositis Ossificans / Q000097:blood*; D014131:Trace Elements / Q000097:blood*; D055815:Young Adult
chemical_list: D016207:Cytokines; D014131:Trace Elements
keywords: Activin A; Copper; Selenium; Zinc