Lessons from Anti-TNF Biologics: Infliximab Failure in a TRAPS Family with the T50M Mutation in TNFRSF1A

  • Belinda Nedjai
  • Niamh Quillinan
  • Robert J. Coughlan
  • Leigh Church
  • Michael F. McDermott
  • Graham A. Hitman
  • Mark D. Turner
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)


Tumour necrosis factor (TNF) receptor-associated syndrome (TRAPS) is a chronic inherited autoinflammatory disorder. Typical features of TRAPS include recurrent fever, myalgia, rashes, and joint and abdominal pains. At the molecular level, TRAPS is associated with autosomal dominant mutations in the gene encoding the 55 kDa TNF receptor (TNFRSF1A). TRAPS affords a unique opportunity to study the biology of TNF in humans, as it is the only human disease currently known to be caused by mutations in the TNFR1 receptor. Although the inflammatory attacks of TRAPS generally fit with the notion of TNF as an inflammatory cytokine, there remain a number of questions to be answered. In particular, why do only certain patients present with cachexia, why do some patients develop systemic amyloidosis and not others, and why is erosive arthritis not seen in TRAPS although it is observed in TNF transgenic mice [20]? Perhaps some of these outcomes are related to the specific mutations seen in TRAPS, whereas others may be the result of still-undefined environmental or genetic factors. With the identification of new TRAPS mutations, it is likely that additional pathogenetic mechanisms will be identified.


Tumour Necrosis Factor Familial Mediterranean Fever Tumour Necrosis Factor Receptor Pyoderma Gangrenosum Certolizumab Pegol 


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Belinda Nedjai
    • 1
  • Niamh Quillinan
    • 2
  • Robert J. Coughlan
    • 2
  • Leigh Church
    • 3
  • Michael F. McDermott
    • 4
  • Graham A. Hitman
    • 1
  • Mark D. Turner
    • 1
  1. 1.Centre for Diabetes, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and DentistryLondonUK
  2. 2.Department of MedicineNational University of IrelandGalwayIreland
  3. 3.Rheumatology Research Group, Division of Immunity and InfectionUniversity of BirminghamEdgbastonUK
  4. 4.Leeds Institute of Molecular Medicine, St. James’ University HospitalLeedsUK

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