title: Expression of receptor for advanced glycation end products in sarcoid granulomas.
abstract: BACKGROUND
  The receptor for advanced glycation end products (RAGE) engages a number of ligands implicated in inflammatory processes. The RAGE coding gene maps to the 6p21.32 region, close to the genes DRB1 and BTNL2, which are associated with sarcoidosis.
  
  
  OBJECTIVE
  We investigated a possible implication of RAGE in sarcoid granulomas.
  
  
  METHODS
  RAGE and major ligands (N-epsilon-carboxy-methyl-lysine [CML], S100A12, and S100B) expression was investigated by immunostaining of 99 paraffin-embedded biopsies of sarcoid tissues, and expression patterns were determined. Among the three RAGE gene single-nucleotide polymorphisms investigated, -374 T/A was selected, characterized in terms of transcriptional effect (immunocytochemistry and real-time polymerase chain reaction), and its frequency was determined in DNA extracted from biopsies.
  
  
  RESULTS
  RAGE, CML, S100A12, and S100B immunoreactivity was observed in all sarcoid granulomas, although at different intensities. The degree of RAGE expression significantly correlated with the degree of S100A12 expression. The -374 TT/AT genotypes, associated with higher RAGE transcriptional activity, were more frequent in the sarcoidosis biopsy group than in control subjects, and the association was confirmed in a second, independent series of 101 patients with sarcoidosis.
  
  
  CONCLUSIONS
  We showed the association of RAGE and its ligands with sarcoidosis and suggest that an intrinsic genetic factor could be in part involved in its expression. In Italian patients, the -374 T/A polymorphism seems to be significantly associated with this disease.
authors.affiliation: Laboratorio di Biochimica & Genetica, Clinica Malattie Apparto Respiratorio, IRCSS Policlinico San Matteo, Università di Pavia, Via Taramelli 5, 27100 Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Campo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Morbini
authors.forename: Michele
authors.initials: M
authors.lastname: Zorzetto
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Brunetta
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Cristina
authors.initials: C
authors.lastname: Bombieri
authors.forename: Mariaclara
authors.initials: M
authors.lastname: Cuccia
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
authors.forename: Valeria
authors.initials: V
authors.lastname: Bozzi
authors.forename: Angelica
authors.initials: A
authors.lastname: Facoetti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ferrarotti
authors.forename: Paola
authors.initials: P
authors.lastname: Mazzola
authors.forename: Roberta
authors.initials: R
authors.lastname: Scabini
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Semenzato
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Pignatti
authors.forename: Ernesto
authors.initials: E
authors.lastname: Pozzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Luisetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D000071797:Butyrophilins; D004247:DNA / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D017127:Glycation End Products, Advanced; D006099:Granuloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D012507:Sarcoidosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C408263:BTNL2 protein, human; D000071797:Butyrophilins; D017127:Glycation End Products, Advanced; D008562:Membrane Glycoproteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D004247:DNA