Arthritis research & therapy
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Arthritis Res. Ther. · Apr 2015
The novel S59P mutation in the TNFRSF1A gene identified in an adult onset TNF receptor associated periodic syndrome (TRAPS) constitutively activates NF-κB pathway.
Mutations in the TNFRSF1A gene, encoding tumor necrosis factor receptor 1 (TNF-R1), are associated with the autosomal dominant autoinflammatory disorder, called TNF receptor associated periodic syndrome (TRAPS). TRAPS is clinically characterized by recurrent episodes of long-lasting fever and systemic inflammation. A novel mutation (c.262 T > C; S59P) in the TNFRSF1A gene at residue 88 of the mature protein was recently identified in our laboratory in an adult TRAPS patient. The aim of this study was to functionally characterize this novel TNFRSF1A mutation evaluating its effects on the TNF-R1-associated signaling pathways, firstly NF-κB, under particular conditions and comparing the results with suitable control mutations. ⋯ The novel S59P mutation leads to defective cellular trafficking and to constitutive activation of TNF-R1. This mutation also determines constitutive activation of the IL-1R pathway, inhibition of apoptosis and enhanced and persistent NF-κB activation and cytokine secretion in response to IL-1β stimulation.
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Arthritis Res. Ther. · Apr 2015
Review Meta AnalysisGout and risk of chronic kidney disease and nephrolithiasis: meta-analysis of observational studies.
To determine the prevalence of chronic kidney disease and nephrolithiasis in people with gout, and the association between gout and prevalent or incident chronic kidney disease and nephrolithiasis. ⋯ Chronic kidney disease and nephrolithiasis are commonly found amongst patients with gout. Gout is independently associated with both chronic kidney disease and nephrolithiasis. Patients with gout should be actively screened for chronic kidney disease and its consequences.