Khaled Elsaid, Tony R Merriman, Leigh-Ana Rossitto, Ru Liu-Bryan, Jacob Karsh, Amanda Phipps-Green, Gregory D Jay, Sandy Elsayed, Marwa Qadri, Marin Miner, Murray Cadzow, Talia J Dambruoso, Tannin Schmidt, Nicola Dalbeth, Ashika Chhana, Jennifer Höglund, Majid Ghassemian, Anaamika Campeau, Nancy Maltez, Niclas G Karlsson, David J Gonzalez, Robert Terkeltaub
OBJECTIVE: In gout, hyperuricemia promotes urate crystal deposition that stimulates the NLRP3 inflammasome and IL-1β-mediated arthritis. Incident gout without background hyperuricemia is rarely reported. To identify hyperuricemia-independent mechanisms driving gout incidence and progression, we characterized erosive urate crystalline inflammatory arthritis meeting ACR/EULAR gout classification criteria in a normouricemic young adult female. METHODS: Whole genome sequencing, quantitative proteomics, whole blood RNA-seq, and IL-1β-induced murine knee synovitis characterized proband candidate genes, biomarkers, and pathogenic mechanisms...
December 1, 2022: Arthritis & Rheumatology