Progress in classification and treatment for TNF receptor-associated periodic syndrome

Abstract

TNF receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder characterized by recurrent febrile attacks. TRAPS is associated with mutation in the gene encoding TNF Receptor I (TNFRI) and seven mutations have been reported in Japan. Molecular modeling experiments indicate that the mutant TNFRI accumulates intracellularly in the endoplasmic reticulum due to misfolding and activates MAP kinase (MAPK) through induction of mitochondrial reactive oxygen species production. MAPK activation is further enhanced by the stimulation through toll-like receptor, resulting in the enhanced proinflammatory cytokine production. Febrile attacks last 21 days on average and occur every one to several months. Myalgia, erythematous macular rash, abdominal pain, conjunctivitis, periorbital edema, chest pain and arthralgia are commonly seen during the attacks. Glucocorticoid is effective in decreasing the severity and duration of the febrile attacks. Soluble TNF receptor etanercept, IL-1 receptor antagonist Anakinra TM and IL-6 receptor antagonist tocilizumab are effective in some patients. Japanese study group of TRAPS conducted national survey to make new diagnostic criteria in 2010. ©2011 The Japan Society for Clinical Immunology.