Blanka Stiburkova (1,2), Jana Mašínová, Andrés Cerezo L( 1), Alquicer G (1), Navrátilová A (1), Pavlíková M, Šenolt L (1)
Affiliation(s):
1. Institute of Rheumatology, Prague, Czech Republic and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
2. Department of Pediatrics and Inherited Metabolic Disorders, Charles University, First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic
Background: IL-40 is a recently described pro-inflammatory cytokine and its role and significance in the pathogenesis of gout has not yet been described.
Objectives: Our aim was to determine the level of IL-40 in the serum of patients with hyperuricemia and/or gout as well as genetic analysis of the gene encoding IL-40 (C17orf99 gene).
Methods: The study cohort collected in Bank of Biological Materials of Institute of Rheumatology included a control group of 48 subjects with no history of primary hyperuricemia/gout, 54 patients with asymptomatic hyperuricemia, 156 patients with intercritical gout, 25 patients with chronic tophaceous gout, 12 patients with acute gouty flares and 84 paediatric hyperuricemia patients. Asymptomatic hyperuricemic patients were classified as having serum uric acid (SUA) > 420 μmol/L for men and SUA > 360 μmol/L for women. Gout patients met the 1977 American Rheumatism Association preliminary classification criteria for acute arthritis of primary gout. Plasma IL-40 was analysed using enzyme-linked immunosorbent assay. The coding regions and intron-exon boundaries of C17orf99 gene were analysed by Sanger sequencing.
Results: Serum IL-40 levels were significantly lower in the control group compared to group of asymptomatic hyperuricemia patients (p < 0.0001), patients with gout (p < 0.0001), patients during acute gout flare (p = 0.0001) and chronic tophaceous gout patients (p = 0.0023). Significantly higher levels were also observed in paediatric patients with hyperuricemia or gout (p < 0.0001). Levels of IL-40 in serum have a slight downward trend with later onset of disease independent of the group: the higher the age of onset, the lower the measured IL-40 value (p = 0.005), estimated decrease 0.91 times (95%CI 0.85-0.97) per 10 years of later onset. Levels of IL-40 in serum were higher among those with higher CRP (p < 0.001) and serum uric acid (off treatment, p < 0.001) levels, independent of the group. Three intron and one allelic exon genetic variants of IL-40 were identified and their associations with the clinical variants of hyperuricemia and gout were evaluated.
Conclusions: We demonstrated the up-regulation of IL-40 levels across the clinical phases of gout: asymptomatic hyperuricemia, intercritical, and chronic tophaceous gout compared to controls and its association with systemic inflammation, uric acid levels and disease onset.
Funded by: Ministry of Health (MH), Czech Republic (CZ), NU22-01-00465, and BBMRICZ LM2023033.