Blanka Stibůrková (1,2), Kateřina Pavelcová (1), Jana Mašínová (1), Lenka Hasikova (1), Karel Pavelka (1), Aleš Kvasnička (3,4, David Friedecký (3,4, Radana Brumarová (3,4), Markéta Pavlíková (5)
Affiliation(s):
1. Institute Of Rheumatology, 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,
3. Laboratory For Inherited Metabolic Disorders, Department Of Clinical Biochemistry, University Hospital, Olomouc, Czech Republic,
4. Faculty Of Medicine And Dentistry, Palacký University Olomouc, Czech Republic,
5. Department of Probability And Mathematical Statistics, Faculty of Mathematics and Physics, Charles University, Prague, Czech Republic
Background: Gout is the most common type of inflammatory arthritis, characterized by chronic deposition of uric acid crystals in the joints. Currently, it is not possible to predict whether patients with hyperuricemia will develop gout, to evaluate the risk of recurrent attacks, or joint damage. Objectives: Our study aimed to use a comprehensive lipidomic analysis approach to identify differences between hyperuricemia, gout, and normouricemia control in age and sex-matched individuals with the purpose to identify differential classes of lipids between early (≤ 40 years) and late-onset, and to deepen understanding on the molecular pathogenesis of gout.
Methods: A targeted lipidomic analysis of more than 600 lipids belonging to 20 lipids (sub)classes consisting of high-performance liquid chromatography coupled with mass spectrometry was used to analyze plasma samples. In total, we analyzed 70 control individuals (47 male), 72 (60 male) patients with early asymptomatic hyperuricemia, 22 (16 male) patients with asymptomatic hyperuricemia, 115 (108 male) patients with early intercritical gout and 81 (69 male) patients with intercritical gout collected in the Bank of Biological Materials of Institute of Rheumatology. Statistical analysis included univariate approaches (effect size evaluation by Cohen's d) and multivariate approaches (PCA, OLPS-DA).
Results: We have discovered more than three times upregulated glycerophospholipids (e.g. log2 average fold changes (log2aFC) of 3.44/3.12 for phosphoethanolamines for un/treated patients) and glycerolipids and more than four times downregulated lysophosphatidylcholines and their plasmalogens (log2aFC of 0.24/0.52 for un/treated patients) in patients. The changes in the lipidome of HUA/Gout≤40 patients indicate an intense impact on lipid metabolism and a severe pathobiochemical effect, with no relationship with common determinants such as ABCG2, BMI, metabolic syndrome, and others. Furthermore, using a supervised multivariate model, we were able to distinguish the Gout≤40 and HUA≤40 patients apart from controls with an overall accuracy of more than 96%
Conclusions: Our findings showed changes in lipidomics metabolism among normouricemia subjects, asymptomatic hyperuricemia, and gout patients. The results indicated significant lipids dysregulation in persons with early-onset hyperuricemia and gout and correction of this imbalance in patients with early urate-lowering treatment.
Acknowledgements: Ministry of Health Czech Republic NU22-01-00465, MH CZ—DRO (FNOL, 00098892), and Ministry of Education, Youth and Sports BBMRI-CZ LM2018125.