Rheumatology Advance Access originally published online on November 15, 2005
Rheumatology 2006 45(1):31-37; doi:10.1093/rheumatology/kei090
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Systemic cytokine levels and the effects of etanercept in TNF receptor-associated periodic syndrome (TRAPS) involving a C33Y mutation in TNFRSF1A
Division of Immunology and Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
Correspondence to: I. Todd, Division of Immunology, A Floor, West Block, Queen's Medical Centre, Nottingham NG7 2UH, UK. E-mail: ian.todd{at}nottingham.ac.uk
Objective. To investigate the levels of the pro-inflammatory cytokines IL-6, TNF-
, IL-1ß, IL-8, IL-10 and IL-12p70 in the plasma of patients with TNF receptor-associated periodic syndrome (TRAPS) in relation to CRP levels and treatment with etanercept.
Methods. Cytokine concentrations were measured in sequential plasma samples obtained from eight patients with a C33Y mutation in TNFRSF1A and diagnosed with TRAPS, using cytokine bead array. The TRAPS samples were compared with samples from normal controls and rheumatoid arthritis patients.
Results. Levels of IL-6 were significantly elevated in C33Y TRAPS patients and these correlated with CRP levels in some of the patients. IL-8 levels were also significantly elevated in the TRAPS patients. However, neither TNF- nor IL-1ß demonstrated a similar increase. This differed from the patients with rheumatoid arthritis, for whom levels of IL-6, IL-8, TNF-, IL-1ß and IL-10 were significantly elevated. The levels of detectable TNF- in the TRAPS patients’ plasma were elevated during etanercept treatment.
Conclusions. The cytokine profile of C33Y TRAPS differs from that of a typical autoimmune inflammatory condition such as rheumatoid arthritis, as only IL-6 and IL-8 were elevated in C33Y TRAPS patients, as distinct from a generalized elevation of pro-inflammatory cytokines. However, only some of the C33Y patients tested showed a relationship between elevated IL-6 and CRP. This is consistent with clinical observations that there is marked heterogeneity between individuals with TRAPS, including those in the same family cohort. Although etanercept has a therapeutic effect in some TRAPS patients, it induces increased plasma concentrations of TNF-, possibly by increasing TNF- stability.
KEY WORDS: TRAPS, TNF receptor, Pro-inflammatory cytokines, Etanercept
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