Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation study.

Objective: To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS).

Methods: Fifteen patients with TRAPS were enrolled in a prospective, open-label, dose-escalation study. Patients recorded attacks, symptom severity, and use of ancillary medications in a daily diary.

Abnormal disulfide-linked oligomerization results in ER retention and altered signaling by TNFR1 mutants in TNFR1-associated periodic fever syndrome (TRAPS).

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominant systemic autoinflammatory disease associated with heterozygous mutations in TNF receptor 1 (TNFR1). Here we examined the structural and functional alterations caused by 9 distinct TRAPS-associated TNFR1 mutations in transfected cells and a mouse "knock-in" model of TRAPS. We found that these TNFR1 mutants did not generate soluble versions of the receptor, either through membrane cleavage or in exosomes.

Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway.

Pyrin, the familial Mediterranean fever protein, is found in association with the cytoskeleton in myeloid/monocytic cells and modulates IL-1beta processing, NF-kappaB activation, and apoptosis. These effects are mediated in part through cognate interactions with the adaptor protein ASC, which shares an N-terminal motif with pyrin. We sought additional upstream regulators of inflammation by using pyrin as the bait in yeast two-hybrid assays.

The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations.

The authors review the genes, and their respective proteins, responsible for eight autoinflammatory conditions. Familial Mediterranean fever is caused by mutations in pyrin, which is the prototype of a new family of proteins belonging to the death-domain superfamily. This new group of proteins, which regulate apoptosis, inflammation, and cytokine processing, share an approximately 90-amino-acid N-terminal sequence called the PYRIN domain.

The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder.

The present report describes and expands the clinical and genetic spectrum of the autoinflammatory disorder, tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS). A total of 20 mutations have been identified since our initial discovery of 6 missense mutations in TNF receptor super family 1A (TNFRSF1A) in 1999. Eighteen of the mutations result in amino acid substitutions within the first 2 cysteine-rich domains (CRDs) of the extracellular portion of the receptor.

Monocytic fasciitis: a newly recognized clinical feature of tumor necrosis factor receptor dysfunction.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a dominantly inherited autoinflammatory syndrome that results from mutations in TNFRSF1A, the gene that encodes the 55-kd tumor necrosis factor receptor. Clinically, patients present with recurrent episodes of fever in conjunction with localized inflammation at various sites. Myalgia is one of the most characteristic features of this syndrome and is frequently associated with an overlying erythematous, macular rash that, together with the myalgia, displays centrifugal migration.