Rationale: 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.Objectives: Weinvestigated a possible implication of RAGE in sarcoid granulomas.Methods: RAGE and major ligands (N-ε-carboxy-methyl-lysine [CML], S100A12, and S100B) expression was investigated by immunostainingof 99 paraffin-embedded biopsies of sarcoid tissues, and expression patternswere determined. Among the three RAGE gene singlenucleotidepolymorphisms 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.Measurements and Results: RAGE, CML, S100A12, and S100B immunoreactivity was observed in all sarcoid granulomas, although atdifferent intensities. The degree of RAGE expression significantly correlated with the degree of S100A12 expression. The -374 TT/ATgenotypes, 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.
Expression of receptor for advanced glycation end products in sarcoid granulomas
Bombieri C.;Pignatti P. F.;
2007-01-01
Abstract
Rationale: 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.Objectives: Weinvestigated a possible implication of RAGE in sarcoid granulomas.Methods: RAGE and major ligands (N-ε-carboxy-methyl-lysine [CML], S100A12, and S100B) expression was investigated by immunostainingof 99 paraffin-embedded biopsies of sarcoid tissues, and expression patternswere determined. Among the three RAGE gene singlenucleotidepolymorphisms 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.Measurements and Results: RAGE, CML, S100A12, and S100B immunoreactivity was observed in all sarcoid granulomas, although atdifferent intensities. The degree of RAGE expression significantly correlated with the degree of S100A12 expression. The -374 TT/ATgenotypes, 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.
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