Immunological features of hyperuricemia and gout phenotypes

Abstract

Current phenotypic classification of hyperuricemia (HU) and gout is based on the presence/absence of monosodium urate (MSU) crystals, clinical signs of gout, and tophi in individuals with elevated uric acid (UA) levels. It is hypothesized that the severity of subclinical inflammation may differ for HU and gout phenotypes. Aim: To test the hypothesis of increasing systemic inflammation intensity with HU progresses in patients within the proposed phenotypic classification. Material and Methods. 220 patients with HU (UA > 360 μmol/L) over 18 years of age were examined and divided into the following phenotypes: asymptomatic HU (AHU); AHU with MSU crystals (verified by ultrasound or synovial fluid analysis) (AHU+crystals); intermittent gout (G); tophaceous gout (G+tophi). Comparative characteristics of the groups included an assessment of the frequency of comorbidities, metabolic disorders, and the main laboratory parameters. Results. According to phenotyping results, the group of patients with AHU consisted of 40 people (18.2%), AHU+crystals – 26 (11.8%), G – 111 (50.5%), G+tophi – 43 (19.5%). The age in the groups was comparable (p = 0.5). An increase in the incidence of arterial hypertension and nephrolithiasis was revealed in the series AHU – AHU+crystals – G – G+tophi ( p = 0.0006 and p = 0.00006, respectively). There was a statistically significant sequential increase in the median value of IL-6 in the groups from AHU to G+tophi ( p = 0.0001). Also, in patients with AHU without MSU crystals, the average serum level of IL-18 was lower than that in the G+tophi group ( p = 0.01). The level of highly sensitive C-reactive protein (hsCRP) was statistically significantly different in patients with AHU compared to patients with G and G+ tophi ( p = 0.04 in both cases). Correlation analysis revealed a weak positive association between UA and IL-6 levels ( r = 0.14, p < 0.05) and UA and hsCRP levels ( r = 0.26, p < 0.05) in the general group ( n = 220). A weak correlation between IL-6 and UA levels was also observed within each group ( p < 0.05 in all cases). A moderate positive correlation was also found between UA and IL-8 levels ( r = 0.36, p < 0.05) in patients in the AHU group ( n = 40). Conclusions. The severity of chronic inflammation in HU is associated with the level of serum UA in the blood and the presence of MSU crystals, and increases during the progression from AHU to chronic tophaceous gout.