Rheumatoid arthritis (RA) is a chronic inflammatory disease that manifests predominantly as synovial inflammation leading to cartilage damage and destruction of the joint infrastructure. Although the joint symptomatology is eventually dominant, the disease is preceded by immune abnormalities that are not joint-specific, but systemic and already apparent many years before onset of the disease. Rheumatoid arthritis (RA) is a symmetric polyarticular arthritis and in addition to inflammation in the synovium, which is the joint lining, the aggressive front of tissue called pannus invades and destroys local articular structures. The synovium is normally a relatively acellular structure with a delicate intimal lining.
Insulin and insulin-like growth factors (IGFs) are polypeptide hormones with high sequence similarity. Insulin has extensive metabolic and mitogenic effects that regulate utilization of carbohydrates, while IGF-1 is an important growth factor involved in cell growth, differentiation, and cell survival. In addition to the canonical IR/IGF-1R signaling pathways, ligation of IGF-1R may lead to cross-talk and induce signaling via receptors belonging to the cytokine receptor family. IGF-1 promotes survival and delays apoptosis of human neutrophils and T lymphocytes, both of which contribute to the pathologic development of inflammatory diseases such as RA.
The age relationship of RA is different from that of organ-specific autoimmune diseases, such as diabetes mellitus or systemic lupus erythematosus that peak earlier in life. The age-inappropriate accelerated telomeric erosion found in lymphocytes of patients with RA could be caused by several mechanisms, either acting alone or in concert. Telomeric erosion could reflect an increased proliferative history of lymphocytes or their precursor cells, or be caused by defective telomerase expression or activity. Alternatively, telomeric shortening could be the result of excessive DNA damage rather than replication-induced telomeric loss. Data on patients with RA indicate that all three of these different mechanisms play a role.