Connecting inflammation, blood vessels and bone in spondyloarthritis

Spondyloarthritis is one of the most frequent forms of chronic inflammatory arthritis, which affects both axial and peripheral joints. Spondyloarthritis is characterized by inflammation, new bone formation and bone destruction. In this disease, the immune system is derailed causing inflammation and previous studies pointed towards an autoinflammatory origin. Symptoms usually appear at a young adult age and chronic tissue inflammation can cause structural damage. Despite the development of novel targeted therapies, treatment-response is still suboptimal in many patients. To improve this, new insights into the multiple disease processes underlying spondyloarthritis pathology are required. Limiting factors in studying spondyloarthritis pathology are that the processes of tissue inflammation and bone formation progress relatively slow and that acquiring of tissue samples is burdensome for patients. In this thesis, the aim was to further unravel the pathological processes associated with bone formation, focusing on the contribution of blood vessels and inflammation. Via a translational approach, using target tissues before and after specific treatments in patients, as well as an experimental spondyloarthritis model, knowledge on the interplay between inflammation, angiogenesis and new bone formation was gained. transmembrane TNF (tmTNF) was identified as a crucial regulator for spondyloarthritis. When further examining bones of the tmTNF mouse model, we demonstrated that tmTNF overexpression leads to ectopic lymphoid structures in bone marrow and specialized blood vessels associated with (pathological) bone formation. Together these findings shed light on the underlying mechanisms of spondyloarthritis pathology and provide a rationale for anti-angiogenic treatment strategies in preventing structural bone damage in spondyloarthritis.