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Published on: March 14, 2019
An improved understanding of pediatric chronic nonbacterial osteomyelitis pathophysiology informs current and future
Eve Roberts1, Amandine Charras1, Gabriele Hahn2
1Department of Women's & Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
Insights
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease. Recent research links NLRP3 inflammasome activation and P2RX7 gene variants to CNO, paving the way for targeted therapies.
Area of Science:
- Immunology
- Genetics
- Pediatric Rheumatology
Background:
- Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease affecting children and young adults.
- Current CNO treatment is largely empirical due to limited understanding of its pathophysiology.
- Imbalance in pro- and anti-inflammatory cytokines, linked to NLRP3 inflammasome activation, is implicated in CNO.
Purpose of the Study:
- To review recent developments in CNO pathophysiology.
- To discuss the impact of these developments on diagnostic and therapeutic strategies for CNO.
- To highlight the role of NLRP3 inflammasome and P2RX7 gene variants in CNO.
Main Methods:
- Review of recent scientific literature on CNO.
- Analysis of studies linking genetic variants and inflammasome activation to CNO.
- Synthesis of findings regarding diagnostic biomarkers and therapeutic targets.
Main Results:
- Elevated pro-inflammatory monocyte-derived protein signatures in CNO patients suggest potential biomarkers.
- Rare variants in the P2RX7 gene are associated with increased NLRP3 inflammasome assembly and monocyte/macrophage survival in CNO.
- Understanding these molecular mechanisms may lead to individualized CNO treatments.
Conclusions:
- Recent advances provide insights into CNO pathogenesis, particularly involving the NLRP3 inflammasome and P2RX7 gene.
- These findings offer potential for developing targeted diagnostic and therapeutic strategies for CNO patients.
- Further research into molecular mechanisms will refine individualized treatment approaches for this autoinflammatory bone disease.
Abstract:
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and young people. It can cause significant pain, reduced function, bone swelling, and even (vertebral body) fractures. Because of a limited understanding of its pathophysiology, the treatment of CNO remains empiric and is based on relatively small case series, expert opinion, and personal experience. Several studies have linked pathological NOD-kike receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation and the resulting imbalance between pro- and anti-inflammatory cytokine expression with CNO. This agrees with elevated pro-inflammatory (mostly) monocyte-derived protein signatures in the blood of CNO patients that may be used as future diagnostic and/or prognostic biomarkers. Recently, rare variants in the P2RX7 gene, encoding for an ATP-dependent transmembrane channel, were linked with increased NLRP3 inflammasome assembly and prolonged monocyte/macrophage survival in CNO. Although the exact molecular mechanisms remain unclear, this will inform future target-directed and individualized treatment. This manuscript reviews most recent developments and their impact on diagnostic and therapeutic strategies in CNO.
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