title: Shedding of mutant tumor necrosis factor receptor superfamily 1A associated with tumor necrosis factor receptor-associated periodic syndrome: differences between cell types.
abstract: OBJECTIVE
  To investigate the effect of mutations in tumor necrosis factor receptor superfamily 1A (TNFRSF1A) on the ability of the receptors to be cleaved from the cell surface upon stimulation. The mutations we studied are associated with clinically distinct forms of TNF receptor-associated periodic syndrome (TRAPS). We also investigated different cell types within the same form of TRAPS.
  
  
  METHODS
  The shedding of TNFRSF1A in response to stimulation with phorbol myristate acetate was assessed in leukocytes and dermal fibroblasts from patients with C33Y TRAPS, and in HEK 293 cell lines stably transfected with constructs containing wild-type TNFRSF1A and/or TNFRSF1A mutants identified in TRAPS patients.
  
  
  RESULTS
  The shedding of TNFRSF1A differed between cell types within the same form of TRAPS. In particular, dermal fibroblasts, but not leukocytes, from C33Y TRAPS patients demonstrated reduced shedding of TNFRSF1A. Shedding of both wild-type and mutant TNFRSF1A from the transfected HEK 293 cells showed minor differences, but was in all cases induced to a substantial extent.
  
  
  CONCLUSIONS
  Differences in TNFRSF1A shedding are not purely a function of the TNFRSF1A structure, but are also influenced by other features of genetic makeup and/or cellular differentiation. It is unlikely that a defect in TNFRSF1A shedding per se can fully explain the clinical features that are common to TRAPS patients with different TNFRSF1A mutations.
authors.affiliation: Division of Immunology, Queen's Medical Centre, University of Nottingham, Nottingham, UK. mary.huggins@nottingham.ac.uk
authors.forename: Mary L
authors.initials: ML
authors.lastname: Huggins
authors.forename: Paul M
authors.initials: PM
authors.lastname: Radford
authors.forename: Richard S
authors.initials: RS
authors.lastname: McIntosh
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bainbridge
authors.forename: Peter
authors.initials: P
authors.lastname: Dickinson
authors.forename: Kelly-Ann
authors.initials: KA
authors.lastname: Draper-Morgan
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Tighe
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Powell
authors.forename: Ian
authors.initials: I
authors.lastname: Todd
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D009154:Mutation; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D013755:Tetradecanoylphorbol Acetate