Hyperuricemia remodels the serum proteome toward a higher inflammatory state

Georgiana Cabău; Orsolya Gaal; Medeea Badii; Valentin Nica; Andreea-Manuela Mirea; Ioana Hotea; HINT-consortium; Cristina Pamfil; Radu A Popp; Mihai G Netea; Simona Rednic; Tania O Crișan; Leo A B Joosten

doi:10.1016/j.isci.2023.107909

Hyperuricemia remodels the serum proteome toward a higher inflammatory state

iScience. 2023 Sep 14;26(10):107909. doi: 10.1016/j.isci.2023.107909. eCollection 2023 Oct 20.

Authors

Georgiana Cabău¹, Orsolya Gaal^{1

2}, Medeea Badii^{1

2}, Valentin Nica¹, Andreea-Manuela Mirea², Ioana Hotea³; HINT-consortium; Cristina Pamfil³, Radu A Popp¹, Mihai G Netea^{2

4}, Simona Rednic³, Tania O Crișan^{1

2}, Leo A B Joosten^{1

2}

Affiliations

¹ Department of Medical Genetics, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
² Department of Internal Medicine, Radboudumc, Nijmegen, the Netherlands.
³ Department of Rheumatology, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
⁴ Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.

Abstract

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.

Keywords: Disease; Health sciences; Proteomics.