ANTI-NUCLEAR ANTIBODY PROFILES DURING ETANERCEPT TREAMENT IN SPONDYLOARTHROPATHY

Background: TNFalpha blockade by the monoclonal antibody infliximab has been shown to induce anti-nuclear antibodies (ANA) in Rheumatoid Arthritis and Spondyloarthropathy (SpA).Objectives: To further assess the role of TNFalpha blockade in the induction of humoral autoimmunity, we studied the effect of etanercept, a soluble TNFalpha receptor, on ANA, anti-dsDNA, anti-nucleosome, anti-histone and anti-extractable nuclear antigen (ENA) antibody profiles in SpA.Methods: Sera from 20 SpA patients treated with etanercept SC (25 mg, twice a week) were obtained at baseline and week 32, and analysed for ANA (indirect immunofluorescence [IIF] on HEp-2000 cells, scored on a 0 to 5+ scale), anti-dsDNA antibodies (IIF on Crithidia luciliae), anti-nucleosome antibodies (ELISA), anti-histone antibodies and anti-ENA antibodies (line immunoassay). A sample was considered positive for ANA if a result > 2+ was obtained. The anti-dsDNA antibodies were further isotyped with gamma-, mu- and alpha-chain specific conjugates at different timepoints.Results: Initially, 6/20 SpA patients tested positive for ANA. After 32 weeks of etanercept treatment, 4/6 patients remained positive, 2 patients became negative and 2 other patients became positive (p=1.000). Only 1 patient had an increase in ANA intensity of at least 2 steps (from 0 at baseline to 2+ at week 32). Furthermore, two patients with negative IIF for anti-dsDNA antibodies at baseline developed positivity for anti-dsDNA antibodies after etanercept treatment (p=0.157). Isotyping revealed that the anti-dsDNA antibodies were of the IgM class and occurred already after 4 to 8 weeks of etanercept treatment. No anti-dsDNA antibodies of the IgG or IgA class were observed. There was no induction of anti-nucleosome antibodies, anti-histone antibodies or anti-ENA antibodies: the few patients with a positive result at baseline remained positive at week 32.Conclusion: In this cohort of 20 SpA patients, TNFalpha blockade by the soluble receptor etanercept during 32 weeks had no major influence on the ANA, anti-nucleosome, anti-histone and anti-ENA profiles. Two patients developed anti-dsDNA antibodies but no anti-dsDNA antibodies of the IgG class nor lupus symptoms were observed.Citation: , volume , supplement , year 2004, page Session: Humoral aspects of autoimmune disease