BACE-1, PS-1 and sAPPβ levels are increased in plasma from sporadic inclusion body myositis patients: surrogate biomarkers among inflammatory myopathies
Sporadic inclusion body myositis (sIBM) is a rare disease which 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...
| Autores: | , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/219049 |
| Acceso en línea: | https://hdl.handle.net/2445/219049 |
| Access Level: | acceso abierto |
| Palabra clave: | Miositis Biòpsia Inflamació Myositis Biopsy Inflammation |
| Sumario: | Sporadic inclusion body myositis (sIBM) is a rare disease which 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 -80ºC. An additional population of patients with non-sIBM inflammatory myopathies was also included (9 patients with dermatomyositis and 5 with polymyositis). Circulating levels of inflammatory cytokines (IL-6 and TNF-α), mitochondrial-related molecules (free plasmatic mtDNA, FGF-21 and CoQ) and amyloidogenic-related molecules (BACE-1, PS-1 and sAPPβ) were assessed with magnetic bead-based assays, rt-PCR, ELISA and HPLC. Despite remarkable trends towards 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 to 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 non-invasive tool for the diagnosis of sIBM, especially in distinguishing this disease from polymyositis. |
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