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

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Advances in TNF Family Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 691))

Abstract

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.

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Author information

Authors and Affiliations

  1. Centre for Diabetes, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Whitechapel, London, E1 2AT, UK

    Belinda Nedjai, Graham A. Hitman & Mark D. Turner

  2. Department of Medicine, National University of Ireland, Galway, Ireland

    Niamh Quillinan & Robert J. Coughlan

  3. Rheumatology Research Group, Division of Immunity and Infection, University of Birmingham, Edgbaston, UK

    Leigh Church

  4. Leeds Institute of Molecular Medicine, St. James’ University Hospital, Leeds, UK

    Michael F. McDermott

Authors
  1. Belinda Nedjai
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  2. Niamh Quillinan
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  3. Robert J. Coughlan
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  4. Leigh Church
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  5. Michael F. McDermott
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  6. Graham A. Hitman
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  7. Mark D. Turner
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Corresponding author

Correspondence to Belinda Nedjai .

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Editors and Affiliations

  1. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    David Wallach

  2. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    Andrew Kovalenko

  3. Kennedy Institute of Rheumatology, Imperial College London, Aspenlea Rd. 1, London, W6 8LH, United Kingdom

    Marc Feldmann

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Nedjai, B. et al. (2011). Lessons from Anti-TNF Biologics: Infliximab Failure in a TRAPS Family with the T50M Mutation in TNFRSF1A . In: Wallach, D., Kovalenko, A., Feldmann, M. (eds) Advances in TNF Family Research. Advances in Experimental Medicine and Biology, vol 691. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6612-4_43

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