2147: Elevated fMET and GDF-15 Circulating Levels in Pediatric CNO Patients with Psoriasis Define a Distinct Mitochondrial-Inflammatory Signature

Background/Purpose: Chronic nonbacterial osteomyelitis (CNO) is a pediatric autoinflammatory bone disorder marked by sterile skeletal inflammation. A subset of CNO patients presents with comorbid psoriasis, suggesting the existence of overlapping inflammatory circuits beyond the musculoskeletal system. Mitochondria-derived formyl peptides (fMET) and the stress-responsive cytokine GDF-15 are emerging as biomarkers of cellular damage and mitochondrial dysfunction, yet their role in CNO, particularly in psoriasis-associated cases, remains poorly defined.

Methods: We analyzed plasma samples from 120 pediatric participants: 30 healthy controls, 30 with inactive CNO, 30 with active CNO, and 30 juvenile idiopathic arthritis (JIA) patients serving as disease controls. Twenty-two participants had comorbid psoriasis (9 CNO-inactive, 11 CNO-active, 2 JIA). Levels of GDF-15 and fMET were analyzed using ELISA. Statistical analysis was conducted in R using ANOVA, Dunn’s multiple comparisons, and unpaired t-tests.

Results: The CNO cohort included 54.2% female participants, with a mean age of 12.56 years. Active and inactive subgroups showed consistent distributions in age and sex. fMET concentrations were significantly elevated in CNO-active patients compared to healthy controls (p < 0.05). GDF-15 levels were significantly higher in participants with comorbid psoriasis compared to those without (p = 0.0312). Notably, within the psoriasis subgroup, patients with active CNO exhibited the highest GDF-15 levels compared to those with inactive disease (p = 0.0044), suggesting enhanced mitochondrial stress when both skeletal and cutaneous inflammation are present.

Conclusion: These findings uncover a distinct immunometabolic profile in pediatric CNO patients with psoriasis, characterized by elevated fMET and GDF-15. This mitochondrial-inflammatory axis may represent a novel endotype within CNO, providing mechanistic insights into extra-skeletal involvement and offering potential avenues for biomarker-guided stratification and targeted therapy.