Autoantibodies and thrombophilia in RA: TNFalpha and TNFalpha blockers

Patients with rheumatoid arthritis (RA) present a median survival much shorter than that of the general population, mainly due to cardiovascular morbidity. Tumour necrosis factor a (TNFa) and interleukin (IL)1b have emerged as crucial mediators of the inflammatory process leading to atherosclerosis. In RA TNFa and IL1b are considered to be the key driving cytokines. A thrombophilic status is mediated by predisposing factors, among which are antiphospholipid antibodies (aPL), markers of an autoimmune thrombophilia. In RA anticardiolipin antibodies (aCL) have been reported in percentages ranging from 11.4% (IgG isotype) to 17.8%, up to 32%. However, no data are available on the relationships existing between the reported increased risk of myocardial infarction in RA and the pro-atherogenic or the thrombophilic status related to the levels of aPL. These issues become even more critical after the introduction of TNFa blockers in clinical practice, drugs extremely efficacious in controlling inflammation, but trials with etanercept and infliximab, have clearly shown the occurrence of aPL. A small percentage of RA patients seem to have a thrombophilic milieu at baseline that might be increased by two possible events, theoretically controllable infections and autoimmunity appearing when TNFa blockers are used. Both events are identifiable, infections can be generally eradicable, autoimmunity can be monitored through specific assays, and once identified it can be carefully assessed over time and might also be given appropriate treatment. The message therefore is the need for careful assessment of infections and autoimmunity and careful monitoring of both features during the follow up.