Conselleria de Sanitat Universal y Salut pública Novelda, Spain
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Maria-Luisa Peral-Garrido1, Paula Boix-Navarro2, Silvia Gómez-Sabater3, Rocío Caño-Alameda3, Alejandra Bermúdez-García4, Teresa Lozano4, Ruth Sanchez-Ortiga4, Miguel Perdiguero4, Elena Caro-Martínez5, Carolina Ruiz-García6, Eliseo Pascual4, Rubén Francés2 and Mariano Andrés4, 1Vinalopó University Hospital, Novelda, Spain, 2Miguel Hernandez University, San Juan de Alicante, Spain, 3Rheumatology Department, Dr. Balmis University General Hospital, Alicante. Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain, 4Dr Balmis Alicante General University Hospital-ISABIAL, Alicante, Spain, 5San Vicente Hospital-HACLE, San Vicente del Raspeig, Spain, 6Campoamor Health Centre, Alicante, Spain
Background/Purpose: Whether the presence of subclinical monosodium urate (MSU) crystal deposition leads to a pro-inflammatory state in asymptomatic hyperuricemia (AH) is unknown. We aimed to compare the inflammatory state in peripheral blood between AH patients with and without sonographic deposits.
Methods: Observational, cross-sectional study. Patients with current serum urate ≥7 mg/dl and no history of acute arthritis were consecutively recruited from internal medicine, cardiology, nephrology, endocrinology, rheumatology, and primary care. We excluded those on urate-lowering treatment or colchicine, another inflammatory rheumatic disease, or being under immunosuppressive therapy (including transplants).
Two comparative groups were predefined. Group 1: AH without deposits; and Group 2: AH with deposits. As sonographic deposits, we considered grade 2-3 double-contour sign and/or tophus according to 2021 OMERACT definitions1, after a 10-location scanning (knees, tibiotalar joints, 1st and 2nd metatarsophalangeal joints, patellar and Achilles tendons) by a trained sonographer blinded to clinical and laboratory data. We measured serum levels of high-sensitivity C-reactive protein (hsCRP) in mg/dl (by immunoturbidimetry), serum amyloid-A in ng/ml (by nephelometry), and erythrocyte sedimentation rate (ESR) in mm/1h, as acute phase reactants. Later, using commercial ELISA kits, we analyzed: i) inflammasome NLRP3-related cytokines: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-18, IL-18 binding protein (IL-18BP); and ii) general pro-inflammatory and anti-inflammatory cytokines: tumor necrosis factor (TNF)-α, IL-6, soluble IL-6 receptor (sIL-6R), and transforming growth factor (TGF)-β.
GraphPad Prism (version 9.5.1) was used to compare AH groups, through Mann-Whitney U's and Chi2 tests.
Results: 77 subjects with AH were recruited, 71.4% men, with a mean age of 59.8 years (SD 17.3) and body mass index (BMI) of 31.2 kg/m2 (SD 5.2). 37.7% and 29.9% had cardiovascular (CVD) and renal disease, respectively. Their mean uric acid was 7.6 mg/dl (SD 1.6).
Patients were classified into group 1 (n=35, 45.5%) or group 2 (n=42, 54.5%). There were no differences (group 2 vs. group 1) in age (67 vs. 56 years), men (69% vs.74.3%), BMI (31.7 vs. 29.9 kg/m2), CVD (38.1% vs. 37.1%), estimated glomerular filtration rate (73.42 vs. 75.03 ml/min/1.73m2), or current serum urate levels (7.35 vs. 7.40 mg/dl). The results of inflammatory markers and cytokines are presented in Figures 1 and 2. There were no differences between groups, but we observed numerical differences for hsCRP, IL-6, and TNF-α.
Conclusion: The inflammatory state was comparable in AH between those with and without sonographic deposits. Some hints were noted for hsCRP, IL-6, and TNF-α that further studies with larger sizes must confirm to establish the relevance of subclinical crystal deposition in AH.
Figure 1. Comparison of acute phase reactants between groups of asymptomatic hyperuricemia. Bars show medians with their 95% confidence intervals. hsCRP: high-sensitivity C reactive protein; SAA: serum A-amyloid protein; ESR: erythrocyte sedimentation rate.
Figure 2. Comparison of cytokines between groups of asymptomatic hyperuricemia. Bars show medians with their 95% confidence intervals. IL-1β: interleukin-1β; IL1-1RA: IL-1 receptor antagonist; IL-18: interleukin-18; IL-18BP: IL-18 binding protein; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; sIL-6R: soluble IL-6 receptor; TGF-β: transforming growth factor-β.
M. Peral-Garrido: None; P. Boix-Navarro: None; S. Gómez-Sabater: None; R. Caño-Alameda: None; A. Bermúdez-García: None; T. Lozano: None; R. Sanchez-Ortiga: None; M. Perdiguero: None; E. Caro-Martínez: None; C. Ruiz-García: None; E. Pascual: None; R. Francés: None; M. Andrés: None.