title: Autoimmunity and anti-TNF-alpha agents.
abstract: Treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor-alpha (anti-TNF-alpha) biologic agents has been associated with a reduction in the levels of specific autoantibodies, such as rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP), and the induction of non- organ-specific autoantibodies (antinuclear antibodies [ANAs], anti-dsDNA, and antiphospholipid antibodies [aPLs]). The mechanisms by which the blockade of anti-TNF-alpha decreases the generation of specific autoantibodies, such as anti-CCP and RF, are not yet known. However, it has been shown that these agents can downregulate the production of several inflammatory cytokines and mediators and that these anti-inflammatory effects may account for reduced autoantibody generation, particularly in the synovial compartment. Infliximab treatment leads to the induction of ANAs in 63.8% of RA patients and 49.1% of Crohn's disease (CD) patients, and anti-dsDNA antibodies in 13% of RA patients and 21.5% of CD patients, respectively. The development of ANAs and anti-dsDNA antibodies has also been described after etanercept therapy in 11% and 15% of RA patients, respectively. In the controlled trials, increases in ANA and anti-dsDNA titers were observed in 5.3% and in 12.9% of adalimumab-treated RA patients. Only limited data on the induction of aPL antibodies during TNF-alpha blocking treatment are available.
authors.affiliation: Rheumatology Unit, Department of Rheumatology, University Hospital L Sacco, Via GB Grassi 74, 20157 Milan, Italy. sarzi@tiscali.it
authors.forename: Fabiola
authors.initials: F
authors.lastname: Atzeni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Turiel
authors.forename: Franco
authors.initials: F
authors.lastname: Capsoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Doria
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Meroni
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Sarzi-Puttini
mesh_terms: D000068879:Adalimumab; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D017152:Antibodies, Antiphospholipid / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis*; D015551:Autoimmunity; D004247:DNA / Q000276:immunology; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D000069285:Infliximab; D010456:Peptides, Cyclic / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor; D012217:Rheumatoid Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000974:Antibodies, Antinuclear; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D004247:DNA; D012217:Rheumatoid Factor; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept