Monocytes from patients with chronic non-bacterial osteomyelitis (CNO) exhibit increased 'classically activated' phenotypes and altered DNA methylation patterns.

Chronic non-bacterial osteomyelitis (CNO) is a rare autoinflammatory bone disease primarily affecting children and adolescents. Reliable biomarkers for diagnosis, disease monitoring, and prediction of disease course are lacking. This study demonstrates that, when compared to healthy participants, the proportion of 'pro-inflammatory' CD14++CD16- 'classical' monocytes is elevated in patients with CNO, before and after the initiation of treatment. Differential DNA methylation (200 hyper-, 162 hypo-methylated) profiles in monocytes from CNO patients affect key genes involved in immune regulation, including RUNX3, HOXA9, HLA-DMB, HLAB, MAP3K6, RXRB, CD163L1, MAP2, CDK6, HLA-G, HDAC10, and HLA-DQA1 genes. Notably, DNA methylation changes persist and potentially progress over time after the initiation of treatment with naproxen. In conclusion, patients with CNO display higher proportions of 'classical' monocytes when compared to healthy participants in conjunction with dysregulated DNA methylation patterns. Molecular alterations remain despite symptom relief with naproxen, suggesting progressive inflammation-mediated changes.