title: Gain and loss of extracellular molecules in sporadic inclusion body myositis and polymyositis--a proteomics-based study.
abstract: Sporadic inclusion body myositis (sIBM) contains non-necrotic myofibers that are surrounded and/or invaded by inflammatory cells. In this study we aimed to identify selective molecules that are present at this site. Myofibers of four biopsies of sIBM that were surrounded and/or invaded by inflammatory cells were microdissected, pooled and profiled by proteomic studies using mass spectrometry. Normal skeletal muscle tissue served as control. Based on the table of proteins that were detected in sIBM only, we selected nine extracellular matrix molecules and validated the results performing immunofluorescence. Seven out of nine proteins that were detected in sIBM by mass spectrometry showed different immunohistochemical results in myositis and normal controls. Of these, the small leucine-rich repeat proteins proline arginine-rich end leucine-rich repeat protein (PRELP) and biglycan were deposited precisely at myofibers surrounded and/or invaded by inflammatory cells both in sIBM and polymyositis. The basement membrane (BM) molecules merosin, perlecan, nidogen-2 and collagen IV were variably destroyed or increased at these sites. P component, which ensheathed all myofibers in normal controls, was absent from invaded myofibers. Similar to BM remodeling, the specific deposition of PRELP and biglycan may represent a mechanism to defend against immune attack. Loss of P component may affect the anchorage of the myofiber in the endomysium.
authors.affiliation: Department of Pathology and Neuropathology, Divison of Neuropathology, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Doppler
authors.forename: Alfred
authors.initials: A
authors.lastname: Lindner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schütz
authors.forename: Monika
authors.initials: M
authors.lastname: Schütz
authors.forename: Antje
authors.initials: A
authors.lastname: Bornemann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000737:chemistry / Q000172:deficiency*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000378:metabolism* / Q000473:pathology; D017285:Polymyositis / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity
chemical_list: D009124:Muscle Proteins