title: Tissue-specific up-regulation of the proteasome subunit beta5i (LMP7) in Sjögren's syndrome.
abstract: OBJECTIVE
  Sjögren's syndrome (SS) is characterized by autoimmune infiltration and focal accumulation of lymphocytes in the exocrine glands, with a predominance of CD4-positive T cells. Since these histologic findings are nonspecific, determination of clinical and serologic abnormalities contribute to the diagnosis. The aim of this study was to identify a novel, disease-specific, immunologically relevant marker for SS.
  
  
  METHODS
  To analyze disease-related and tissue-specific expression of candidate markers, we examined biopsied minor salivary glands and peripheral blood mononuclear cells from patients with primary and secondary SS (n = 26) as well as from patients with sicca symptoms without autoimmune sialadenitis (n = 15). Expression of the Th1/Th2-related chemokines CCL3 (macrophage inflammatory protein 1alpha) and CCL2 (monocyte chemoattractant protein 1), CXCL7 (neutrophil-activating peptide 2 [NAP-2]), interleukin-1beta, inducible costimulator, and the proteasome subunits alpha3 (C9) and beta5i (LMP7) was analyzed at the messenger RNA (mRNA) level using real-time polymerase chain reaction techniques. Immunohistochemical analysis was used to identify the beta5i (LMP7)-expressing cell populations in minor salivary glands.
  
  
  RESULTS
  The expression profiles revealed a significant up-regulation of beta5i (LMP7) exclusively in the salivary glands of SS patients. Immunohistochemistry confirmed expression of the immunoproteasome subunit beta5i (LMP7) within the acinar and ductal epithelial cells. No significant difference in the distinct histologic focus scores was evident for the expression of the markers investigated. In the peripheral blood compartment, the expression of CXCL7 was up-regulated both in primary and in secondary SS.
  
  
  CONCLUSIONS
  Tissue-specific up-regulation of beta5i (LMP7) mRNA was shown to be characteristic of SS, indicating a disease-specific modulation of the proteasome system. Expression of beta5i (LMP7) represents an independent parameter that can be used in addition to the focus score to distinguish SS in biopsied labial salivary glands.
authors.affiliation: Charité Universitätsmedizin Berlin, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Egerer
authors.forename: Lorena
authors.initials: L
authors.lastname: Martinez-Gamboa
authors.forename: Anja
authors.initials: A
authors.lastname: Dankof
authors.forename: Bruno
authors.initials: B
authors.lastname: Stuhlmüller
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
authors.forename: Veit
authors.initials: V
authors.lastname: Krenn
authors.forename: Karl
authors.initials: K
authors.lastname: Egerer
authors.forename: Paul E
authors.initials: PE
authors.lastname: Rudolph
authors.forename: Gerd-R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Eugen
authors.initials: E
authors.lastname: Feist
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics / Q000276:immunology*; D011446:Prospective Studies; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000096:biosynthesis; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D009097:Multienzyme Complexes; D012333:RNA, Messenger; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex