Hyperuricemia remodels the serum proteome toward a higher inflammatory state
Georgiana Cabău,
Orsolya Gaal,
Medeea Badii,
Valentin Nica,
Andreea-Manuela Mirea,
Ioana Hotea,
Cristina Pamfil,
Radu A. Popp,
Mihai G. Netea,
Simona Rednic,
Tania O. Crișan,
Leo A.B. Joosten
Affiliations
Georgiana Cabău
Department of Medical Genetics, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Orsolya Gaal
Department of Medical Genetics, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; Department of Internal Medicine, Radboudumc, Nijmegen, the Netherlands
Medeea Badii
Department of Medical Genetics, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; Department of Internal Medicine, Radboudumc, Nijmegen, the Netherlands
Valentin Nica
Department of Medical Genetics, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Andreea-Manuela Mirea
Department of Internal Medicine, Radboudumc, Nijmegen, the Netherlands
Ioana Hotea
Department of Rheumatology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Cristina Pamfil
Department of Rheumatology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Radu A. Popp
Department of Medical Genetics, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Mihai G. Netea
Department of Internal Medicine, Radboudumc, Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
Simona Rednic
Department of Rheumatology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Tania O. Crișan
Department of Medical Genetics, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; Department of Internal Medicine, Radboudumc, Nijmegen, the Netherlands
Leo A.B. Joosten
Department of Medical Genetics, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; Department of Internal Medicine, Radboudumc, Nijmegen, the Netherlands; Corresponding author
Summary: Gout is an autoinflammatory disease triggered by a complex innate immune response to MSU crystals and inflammatory triggers. While hyperuricemia is an obligatory risk factor for the development of gout, the majority of individuals with hyperuricemia never develop gout but have an increased risk of developing cardiometabolic disorders. Current management of gout aims at MSU crystal dissolution by lowering serum urate. We apply a targeted proteomic analysis, using Olink inflammation panel, to a large group of individuals with gout, asymptomatic hyperuricemia, and normouricemic controls, and we show a urate-driven inflammatory signature. We add in vivo evidence of persistent immune activation linked to urate exposure and describe immune pathways involved in the pathogenesis of gout. Our results support a pro-inflammatory effect of asymptomatic hyperuricemia and pave the way for new research into targetable mechanisms in gout and cardiometabolic complications of asymptomatic hyperuricemia.
