title: Anti-nucleosome antibodies as prediction factor of development of autoantibodies during therapy with three different TNFalpha blocking agents in rheumatoid arthritis.
abstract: Anti-nucleosome antibodies have a role in the diagnosis and follow-up of systemic lupus erythematosus (SLE) and have a possible correlation with SLE activity and with kidney and hematological involvement. The aim of our study was to detect in 91 patients with rheumatoid arthritis (RA) the positivity of anti-nucleosome antibodies during therapy with three different TNFalpha blocking agents and to underline the possible correlation with the development of antinuclear autoantibodies (ANA) and anti-dsDNA autoantibodies. We detected anti-nucleosome antibodies, ANA, and anti-dsDNA during therapy with three different TNFalpha blocking agents at T-0 and after 12 and 24 weeks of treatment, respectively. Anti-nucleosome antibodies (IgG class) were analyzed by ELISA technique (Orgentec Diagnostika GmbH, Mainz, Germany), ANA both by indirect immunofluorescence (IIF) technique on Hep-2 (Scimedx, USA) and by ELISA (Autoimmune EIA ANA screening test Bio-Rad Laboratories, CA, USA), and anti-dsDNA (IgG and IgM classes) by ELISA (Kallestad, Bio-Rad Laboratories, CA, USA) and confirmed by IIF on Crithidia luciliae (ImmunoConcepts N.A., Sacramento, CA, USA). We observed 19 patients on infliximab treatment at 3 mg/kg every 8 weeks, 43 patients on etanercept treatment at 25 mg twice a week, and 29 patients on adalimumab treatment at 40 mg every other week. At baseline, we observed positivity as follow: in the group of patients treated with infliximab-anti-nucleosome 1/19 (5.26%), ANA 3/19 (15.7%), anti-dsDNA 1/19 (5.26%); in the group treated with etanercept--anti-nucleosome 2/43 (4.65%), ANA 1/43 (2.43%), anti-dsDNA 0/43; and in the group treated with adalimumab--anti-nucleosome 2/29 (6.89%), ANA 1/29 (3.44%), anti-dsDNA 0/29. The results at 12 weeks for the three autoantibodies were: for infliximab--3/19 (15.7%), 10/19 (52.6%), 2/19 (10.5%); for etanercept--3/43 (6.9%), 10/43 (23.2%), 1/43 (2.32%); and for adalimumab--3/29 (10.3%), 4/29 (13.7%), 1/29 (3.4%). At 24 weeks, the results were for infliximab 6/19 (31.5%), 12/19 (63.1%), 2/19 (10.5%); for etanercept 11/43 (25.5%), 22/43 (51.1%), 2/43 (4.65%); and for adalimumab 4/29 (13.7%), 13/29 (44.8%), 1/29 (3.4%). We observed a concordance anti-nucleosome/ANA antibodies of 85.5% (p < 0.001). Our data showed a concordance between anti-nucleosome antibodies and ANA positivity in patients with RA during therapy with TNFalpha blocking agents. The induction of autoantibodies positivity is different for each TNFalpha blocking agent.
authors.affiliation: Rheumatology Unit, Nuovo Ospedale S. Giovanni di Dio, ASL 10, via di Torregalli 3, Florence, Italy. maubenucci@tiscali.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Benucci
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Saviola
authors.forename: Paola
authors.initials: P
authors.lastname: Baiardi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cammelli
authors.forename: Mariangela
authors.initials: M
authors.lastname: Manfredi
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D000068800:Etanercept; D019084:Fluorescent Antibody Technique, Indirect; D006304:Health Status; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008875:Middle Aged; D009707:Nucleosomes / Q000276:immunology*; D011237:Predictive Value of Tests; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001323:Autoantibodies; D007074:Immunoglobulin G; D009707:Nucleosomes; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept