Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0008031 (chest pain)
 17,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:[Progress in classification and treatment for TNF receptor-associated periodic syndrome]. 2204 23

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory syndrome characterized by prolonged and recurrent episodes of fever, abdominal and/or chest pain, arthralgia, myalgia, and erythematous rash. TRAPS is associated with heterozygous variants in the TNFRSF1A gene, which encodes the TNFR1 (tumor necrosis factor receptor 1) receptor. Disease-causing variants are found exclusively in the extracellular domain of TNFR1 and affect receptor structure and binding to the TNF ligand. The precise mechanism of the disease is still unclear, but it is thought that intracellular accumulation of misfolded mutant protein leads to endoplasmic reticulum stress and enhanced inflammatory responses through constitutive activation of various immune pathways. Other possible mechanisms contributing to the disease pathogenesis include defective receptor shedding, TNF-induced cell death, production of reactive oxygen species, and autophagy impairment. Patients' leucocytes are hyperresponsive to stimulation and produce elevated levels of proinflammatory cytokines. Systemic autoimmune (AA) amyloidosis is an important cause of morbidity and mortality in TRAPS. Over the last two decades, new therapies have changed the progression and outcome of the disease. In this review, we summarize clinical data from 209 patients with validated pathogenic variants reported in the literature and discuss TRAPS diagnosis, pathogenesis, and treatment options.
 ...
PMID:Revisiting TNF Receptor-Associated Periodic Syndrome (TRAPS): Current Perspectives. 3238 Jul 4