The role of lymphotoxin-α in rheumatoid arthritis

Background The role of tumor necrosis factor (TNF) in the inflammatory response in rheumatoid arthritis (RA) is well established, whereas less is known about the role of TNF's close homolog, lymphotoxin alpha (LT alpha). Findings Increased levels of LT alpha are found in the serum and synovial tissue of patients with RA, and in vitro studies found that LT alpha-induced proliferation of RA fibroblast-like synoviocytes was at a similar level to TNF. These findings support the idea that anti-LT alpha treatment could be beneficial in patients with RA, but pateclizumab, an anti-LT alpha antibody, was not as efficacious as the anti-TNF agent adalimumab in reducing symptoms of RA in a head-to-head study, suggesting that anti-LT alpha therapies might not represent a valid alternative treatment option in patients with RA. However, suppression of LT alpha activity might be relevant in the context of RA-related comorbidities, as patients with RA have an increased risk of myocardial infarction (MI) compared with the general population, and specific polymorphisms of the LT alpha gene have been linked to increased MI risk. Conclusions In this review, we summarize the key characteristics of LT alpha and the most recent findings on the role of LT alpha in RA.