Falling into TRAPS – receptor misfolding in the TNF receptor 1-associated periodic fever syndrome

Fiona C Kimberley¹ , Adrian A Lobito² , Richard M Siegel³ and Gavin R Screaton⁴

¹Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

²Genetech, 1 DNA Way, MS 63, South San Francisco, CA 94080, USA

³Immunoregulation Unit, Autoimmunity Branch, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA

⁴Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK

author email corresponding author email

Arthritis Research & Therapy 2007, 9:217doi:10.1186/ar2197


Published:	23 July 2007

Abstract

TNF receptor-associated periodic syndrome (TRAPS) is a dominantly inherited disease caused by missense mutations in the TNF receptor 1 (TNFR1) gene. Patients suffer from periodic bouts of severe abdominal pain, localised inflammation, migratory rashes, and fever. More than 40 individual mutations have been identified, all of which occur in the extracellular domain of TNFR1. In the present review we discuss new findings describing aberrant trafficking and function of TNFR1 harbouring TRAPS mutations, challenging the hypothesis that TRAPS pathology is driven by defective receptor shedding, and we suggest that TNFR1 might acquire novel functions in the endoplasmic reticulum, distinct from its role as a cell surface receptor. We also describe the clinical manifestations of TRAPS, current treatment regimens, and the widening array of patient mutations.