title: Thrombogenicity of TNF alpha in rheumatoid arthritis defined through biological probes: TNF alpha blockers.
abstract: Rheumatoid arthritis is a disease at high cardiovascular risk. It has recently been shown that RA patients with more than 10 years disease duration present a risk of myocardial infarction more than three times higher than osteoarthritis controls. The major determinant is thought to be the chronic inflammatory process, driven by some key cytokines among which TNF alpha is thought to play the leading role in the majority of the patients. TNFalpha, therefore, once blocked by specific inhibitors like TNF alpha blockers (Infliximab, Etanercept) should profoundly decrease the cardiovascular risk. However, TNF blockers induce the appearance of autoimmunity though in a small minority of the patients. This autoimmunity is thought to be due to the poor clearance of apoptotic bodies once the systemic inflammation (CRP, SAP) is controlled by the specific blockers, and to the lack of control of some B cell populations producing autoantibodies to specific autoantigens. Among the autoantibodies arising during TNF blockade, anticardiolipin appear to be the most crucial with respect to the cardiovascular risk. The appearance of anticardiolipins at clinically significant levels appears to be driven by two possible mechanisms, one due to common infections of the urinary or upper airways tract during blockade of soluble TNF alpha, the other due to the escape of some autoreactive B cells during blockade of soluble and membranous TNF alpha. Since both autoantibodies related to infections as well as the high levels unrelated to infections, can be well controlled by appropriate therapies, clinicians should pay attention to the biological phenomenon before it becomes a clinical problem.
authors.affiliation: Division of Rheumatology, DPMSC, School of Medicine, University of Udine, Udine 33100, Italy. gf.ferraccioli@med.uniud.it
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
authors.forename: Elisa
authors.initials: E
authors.lastname: Gremese
mesh_terms: D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012307:Risk Factors; D019851:Thrombophilia / Q000139:chemically induced*; D013927:Thrombosis / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept