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the tumour necrosis factor receptor-associated periodic syndrome: current concepts

Published online by Cambridge University Press:  10 October 2005

silvia stojanov
Affiliation:
genetics and genomics branch, niams, national institutes of health, building 9, room 1w111, 9 memorial drive, bethesda, md 20892-0908, usa.
michael f. mcdermott
Affiliation:
academic unit of musculoskeletal disease, university of leeds, clinical science building, st. james's university hospital, beckett street, leeds, ls9 7tf,uk.

Abstract

the tumour necrosis factor receptor (tnfr)-associated periodic syndrome (traps) is an autosomal dominant, multisystemic, autoinflammatory disorder caused by mutations in the tnfr1 gene (tnfrsf1a). traps seems to be the most common hereditary periodic fever (hpf) syndrome in some western populations, and the second most prevalent hpf worldwide, behind familial mediterranean fever (fmf). the proteins involved in susceptibility to traps (tnfrsf1a) and fmf (pyrin) are both members of the death-domain-fold superfamily. mutations affecting these proteins might cause dysregulation of innate immune responses, with a propensity to autoinflammation. most traps patients have reduced blood levels of soluble tnfrsf1a between attacks, with an inappropriately small increase during bouts of fever. the pathogenesis of the ‘hyperinflammatory state’ in traps has been variously ascribed to a shedding defect of tnfrsf1a from the cell surface resulting in increased tnf inflammatory signalling, or impaired tnf apoptotic signalling. some low-penetrance tnfrsf1a variants also contribute to the clinical phenotype in individuals carrying other hpf-associated mutations, and have been reported in several disorders such as behçet's disease and systemic lupus erythematosus. synthetic anti-tnf agents provide a rational form of therapy for traps, and have been shown to delay or indeed prevent development of systemic amyloidosis (aa type), a life-threatening complication in this condition.

Type
Review Article
Copyright
cambridge university press 2005

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Footnotes

dr silvia stojanov's contributions are a work of the united states government and are not protected by copyright in the united states.