title: BACE-1, PS-1 and sAPPβ Levels Are Increased in Plasma from Sporadic Inclusion Body Myositis Patients: Surrogate Biomarkers among Inflammatory Myopathies.
abstract: Sporadic inclusion body myositis (sIBM) is a rare disease that is difficult to diagnose. Muscle biopsy provides three prominent pathological findings: inflammation, mitochondrial abnormalities and fibber degeneration, represented by the accumulation of protein depots constituted by β-amyloid peptide, among others. We aim to perform a screening in plasma of circulating molecules related to the putative etiopathogenesis of sIBM to determine potential surrogate biomarkers for diagnosis. Plasma from 21 sIBM patients and 20 age- and gender-paired healthy controls were collected and stored at -80°C. An additional population of patients with non-sIBM inflammatory myopathies was also included (nine patients with dermatomyositis and five with polymyositis). Circulating levels of inflammatory cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-α), mitochondrial-related molecules (free plasmatic mitochondrial DNA [mtDNA], fibroblast growth factor-21 [FGF-21] and coenzyme-Q10 [CoQ]) and amyloidogenic-related molecules (beta-secretase-1 [BACE-1], presenilin-1 [PS-1], and soluble Aβ precursor protein [sAPPβ]) were assessed with magnetic bead-based assays, real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA) and high-pressure liquid chromatography (HPLC). Despite remarkable trends toward altered plasmatic expression of inflammatory and mitochondrial molecules (increased IL-6, TNF-α, circulating mtDNA and FGF-21 levels and decreased content in CoQ), only amyloidogenic degenerative markers including BACE-1, PS-1 and sAPPβ levels were significantly increased in plasma from sIBM patients compared with controls and other patients with non-sIBM inflammatory myopathies (p< 0.05). Inflammatory, mitochondrial and amyloidogenic degeneration markers are altered in plasma of sIBM patients confirming their etiopathological implication in the disease. Sensitivity and specificity analysis show that BACE-1, PS-1 and sAPPβ represent a good predictive noninvasive tool for the diagnosis of sIBM, especially in distinguishing this disease from polymyositis.
authors.affiliation: Laboratory of Muscle Research and Mitochondrial Function, Cellex-IDIBAPS, Faculty of Medicine, University of Barcelona, Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Catalán-García
authors.affiliation: Laboratory of Muscle Research and Mitochondrial Function, Cellex-IDIBAPS, Faculty of Medicine, University of Barcelona, Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Glòria
authors.initials: G
authors.lastname: Garrabou
authors.affiliation: Laboratory of Muscle Research and Mitochondrial Function, Cellex-IDIBAPS, Faculty of Medicine, University of Barcelona, Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Constanza
authors.initials: C
authors.lastname: Morén
authors.affiliation: Laboratory of Muscle Research and Mitochondrial Function, Cellex-IDIBAPS, Faculty of Medicine, University of Barcelona, Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Guitart-Mampel
authors.affiliation: Laboratory of Muscle Research and Mitochondrial Function, Cellex-IDIBAPS, Faculty of Medicine, University of Barcelona, Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Gonzalez-Casacuberta
authors.affiliation: Laboratory of Muscle Research and Mitochondrial Function, Cellex-IDIBAPS, Faculty of Medicine, University of Barcelona, Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Hernando
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Biomedicine (University of Barcelona), University of Barcelona, and CIBEROBN, Barcelona, Spain.
authors.forename: Jose Miquel
authors.initials: JM
authors.lastname: Gallego-Escuredo
authors.affiliation: Clinical Biochemistry Department, Hospital Sant Joan de Déu, Barcelona, Spain, and CIBERER, Valencia, Spain.
authors.forename: Dèlia
authors.initials: D
authors.lastname: Yubero
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Biomedicine (University of Barcelona), University of Barcelona, and CIBEROBN, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
authors.affiliation: Clinical Biochemistry Department, Hospital Sant Joan de Déu, Barcelona, Spain, and CIBERER, Valencia, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Montero
authors.affiliation: Internal Medicine Department, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Albert Selva
authors.initials: AS
authors.lastname: O-Callaghan
authors.affiliation: Laboratory of Muscle Research and Mitochondrial Function, Cellex-IDIBAPS, Faculty of Medicine, University of Barcelona, Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
authors.affiliation: Laboratory of Muscle Research and Mitochondrial Function, Cellex-IDIBAPS, Faculty of Medicine, University of Barcelona, Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Grau