“A number of known factors may contribute to chronicity: the structural properties of HLA-B27, activation of the immune system by the presence of inflammatory bowel disease or infection, and polymorphisms in cytokines and cytokine processing molecules that lead to either more severe inflammation or delayed clearance of inflammation,” they said.
Development of SpA, therefore, is dependent on a complicated process resulting in chronic or recurrent inflammation, “but also to the triggering of new tissue formation, completely or partially independent of inflammation,” Dr. Lories and colleagues wrote.5
Current evidence from animal models suggests that “inflammation and new bone formation are linked but are largely molecularly uncoupled processes,” he said. The triggering of inflammation clearly leads to tissue destruction.
“The relationship between biomechanical stress, micro damage, acute inflammation and chronic activation of the immune system should be high on the research agenda,” Dr. Lories said. Current therapies only target the pain and symptoms of the disease.
Molecular Level
Dominique Baeten, MD, PhD, associate professor in Academic Medical Centrum in Amsterdam, said that much is still not known about bone formation and destruction in AS. “We don’t really know what is happening at the molecular level, and we can’t really connect it to the clinic right now.”
In his presentation of several hypotheses, Dr. Baeten suggested that there may be different kinds of inflammation that have implications for connective tissue, cartilage, and bone. “Triggering of inflammation clearly leads to tissue destruction. Perhaps by slightly different cytokines or inflammatory mediators, it can lead to tissue formation.”
There may also be another pathway through stromal activation directly to tissue formation, he said. “Very importantly, the mechanism may be completely different if you look at the synovial joint as we do in rheumatoid arthritis, or at the sacroiliac joint or peripheral joints.”
Kathy Holliman is a medical journalist based in New Jersey.
References
- Davis JC, van der Heijde DM, Braun J, et al. Sustained durability and tolerability of etanercept in ankylosing spondylitis for 96 weeks. Ann Rheum Dis. 2005;64:1557-1562.
- van der Heijde D, Landewe R, Baraliakos X, et al. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum. 2008;58:3063-3070.
- van der HD, Schiff MH, Sieper J, et al. Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: Long-term results from the ATLAS trial. Ann Rheum Dis. 2009;68:922-929.
- van der Heijde D, Salonen D, Weissman BN, et al. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther. 2009;11:R127.
- Lories RJ, Luyten FP, de Vlam K. Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis. Arthritis Res Ther. 2009;11:221.