RT Journal Article SR Electronic T1 Candidate Genes in Patients with Autoinflammatory Syndrome Resembling Tumor Necrosis Factor Receptor-associated Periodic Syndrome Without Mutations in the TNFRSF1A Gene JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP 1378 OP 1384 DO 10.3899/jrheum.101260 VO 38 IS 7 A1 SILVIA BORGHINI A1 MICHELE FIORE A1 MARCO Di DUCA A1 FRANCESCO CAROLI A1 MARTINA FINETTI A1 GIUSEPPE SANTAMARIA A1 FRANCESCA FERLITO A1 FEDERICO BUA A1 PAOLO PICCO A1 LAURA OBICI A1 ALBERTO MARTINI A1 MARCO GATTORNO A1 ISABELLA CECCHERINI YR 2011 UL http://www.jrheum.org/content/38/7/1378.abstract AB Objective. Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal-dominant multisystemic autoinflammatory condition. Patients display different mutations of the TNF receptor superfamily 1A gene (TNFRSF1A), coding for a nearly ubiquitous TNF receptor (TNFR1). No TNFRSF1A mutation has been identified in a proportion of patients with TRAPS-like phenotype. Methods. We investigated mechanisms downregulating the TNF-induced inflammatory response such as (1) receptor shedding, producing a secreted form acting as a TNF inhibitor; (2) receptor internalization with subsequent induction of apoptosis; and (3) negative regulation of nuclear factor-κB (NF-κB) transcription. We analyzed the sequence of genes known to play a pivotal role in these pathways, in 5 patients with TRAPS symptoms and showing shedding and/or apoptosis defects, but without mutations of the TNFRSF1A gene. Results. Sequence analysis of 3 genes involved in TNFR1 shedding (ERAP1, NUCB2, RBMX) and 3 genes involved in negative regulation of NF-κB signaling (TNFAIP3, CARP-2) or NF-κB transcription (ZFP36) revealed only a few unreported variants, apparently neutral. Conclusion. Our study rules out any involvement in the pathogenesis of TRAPS of some of the genes known to regulate TNFR1 shedding and TNF-induced NF-κB signaling and transcription. Gene(s) responsible for TRAPS-like syndrome remain to be investigated among currently unidentified genes likely involved in these pathways, or by applying the genome-wide function-free sequencing approach.