Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia
Authors' conclusion
Our findings linked normouricemic erosive gout to attenuated lubricin, with impaired control of cathepsin G activity, compounded by deleterious NLRP3 variants.
Study context
- Population
- Young female patient with normouricemia and erosive urate crystalline inflammatory arthritis meeting American College of Rheumatology (ACR)/EULAR gout classification criteria (the proband)single proband
- Outcome
- Hyperuricemia-independent mechanisms in normouricemic erosive gout (proband): lubricin level, gene variants, cathepsin G activity, and lubricin/TLR-2 effects in cells and mice
Methodological detailssingle-patient (proband) case study, whole-genome sequencing, quantitative proteomics, whole-blood RNA-sequencing, mouse model of IL-1β-induced knee synovitis
- Single-patient (proband) case study
- Whole-genome sequencing
- Quantitative proteomics
- Whole-blood RNA-sequencing
- Mouse model of IL-1β-induced knee synovitis
Main finding
As reported in the abstract
- TLR-2 activation suppressed lubricin mRNA and lubricin release in cultured human synovial fibroblasts
- P < 0.01
- Lubricin blunted urate crystal precipitation and IL-1β induction of xanthine oxidase and urate in cultured macrophages
- P < 0.001
- In lubricin-deficient mice, IL-1β knee injection increased xanthine oxidase-positive synovial resident M1 macrophages
- P < 0.05
Original publication
Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia. Arthritis Rheumatol. Published 10 March 2023. doi:10.
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