SP0187 PATHOPHYSIOLOGY AND THERAPEUTIC CONSEQUENCES AUTO-INFLAMMATORY BONE DISORDERS

Abstract

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder, covering a clinical spectrum with asymptomatic inflammation of single bones at the one end, and chronic recurrent multifocal osteomyelitis (CRMO) at the other end. Bone inflammation, however, can also be a symptom of other autoimmune/inflammatory conditions. Rare monogenic autoinflammatory diseases with bone involvement have informed research and provide models for the more common and pathophysiologically complex disorder CNO/CRMO. Despite recent efforts, the exact molecular pathophysiology of CNO remains incompletely understood. Profound dysregulation of cytokine responses was demonstrated in CNO/CRMO. Failure to produce antiinflammatory cytokines interleukin (IL)-10 and IL-19 contributes to activation of inflammasomes and subsequent IL-1β release. In IL-10-deficient and in CNO-prone chronic multifocal osteomyelitis mice, IL-1β was linked to bone inflammation. Recently, increased inflammasome component expression and inflammasome assembly have been linked with CNO/CRMO in humans. Furthermore, alterations to the gut microbiome were suggested in contributing to IL-1β release from innate immune cells in mice, offering an interesting target in the search for molecular mechanisms in CNO. This presentation will review molecular alterations in autoinflammatory bone disease, focussing on CNO and discuss therapeutic consequences.