TNF-α

Ligand for TNFR1 — upstream trigger

Expression
Elevated during attacks
Evidence level
established
Targeted by
Etanercept (partial)

Role in pathogenesis

TNF-α is the principal ligand for TNFR1. In TRAPS, autocrine TNF secretion and wild-type TNFR1 on the cell surface amplify inflammation. Paradoxically, anti-TNF monoclonal antibodies (infliximab) can worsen disease, while soluble receptor mimetic etanercept has partial efficacy.

Targeting drugs (1)

DrugMechanismResponseLine
EtanerceptSoluble TNF receptor fusion protein (TNFR2-Fc)Partial, waning over timeAlternative

Sources (3)

DetailsSimon A et al. (2010) Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndrome · Proc Natl Acad Sci USADOI ↗
DetailsMcDermott MF et al. (1999) Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes · CellDOI ↗
DetailsHull KM et al. (2012) Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome (TRAPS): a prospective, open-label, dose-escalation study · Arthritis RheumDOI ↗