AUTOANTIBODIES PROFILE OF RHEUMATOID ARTHRITIS (RA) DURING INFLIXIMAB (INFL) TREATMENT

Background: Anti TNF-alpha (both INFL and etanercept) can induce the production of antinuclear (ANA) and anti DNAds antibodies, although the clinical emergence of a lupus-like syndrome is infrequent. No data are at present available about other autoantibodies, such as anti-CCP antibodies, a highly sensitive and specific serological marker of RA, or antikeratin antibodies (AKA), ANCA, and other ANA specificities (namely anti hystone - AHA -, anti nucleosome - ANS - and anti DNAss antibodies).Objectives: To evaluate the serological autoimmune profile of RA patients treated with infliximab.Methods: Fifty-four sera from 6 RA patients (median INFL infusion/patient 7.5, range 3-12) and, as controls, 18 sera from 4 active spondyloarthritis in inflammatory bowel disease patients (IBD-SA, (median INFL/patient 5, range 3-7) were tested for the following 10 autoantibodies: 1. ANA by IFL on HEp-2 cells(1:20 dilution); 2. antiDNAds by IFL on Crithidia luciliae (CL) (1:20 dilution, with sheep anti-human Ig as secondary antibody); 3. IgG antiDNAds by ELISA (DIAMEDIX, Fl, USA); 4. IgG antiDNAss by ELISA (DIAMEDIX, Fl, USA); 5. IgG AHA by ELISA (DIAMEDIX, Fl, USA); 6. IgG ANS by ELISA (DIAMEDIX, Fl, USA); 7. anti-ENA by counterimmunoelectrophoresis; 8. IgG anti-CCP (AXIX-SHIELD, UK); 9. IgG AKA by IFL on rat oesophagus (dilution 1:20) and 10. ANCA by IFL on cytospin preparation of human blood peripheral granulocytes (1:20 dilution, with sheep anti-human Ig as secondary antibody).Results: ANA: one RA patient and none IBD-SA was positive for ANA before INFL, while all of them became positive after 1-5 infusions. No differences were found between the groups, both in terms of time and pattern (mainly speckled and homogeneous). As to IFL anti DNAds, all patients were negative before INFL while four out of 6 (67%) RA and 1out of 4 (25%) IBD-SA became positive during treatment (after 1-10 infusions), with titres up to 1/320. This positivity was lost after 1-4 infusions (8-32 weeks). The appearance of the antibody was not associated to any clinical relevant effect. All sera tested, including IFL antiDNA positive ones, were negative for IgG anti DNAds when tested by ELISA. As to antiCCP, 3 RA and none IBD-SA patients were positive before INFL. The antibody did not change its titre during treatment and no patient acquired or lost it. The same happened to AKA. All sera turned out to be anti-ENA negative. As to all the other specificities (antissDNA, ANS, AHA, ANCA), INFL induced their transient and at low titre in a very low proportion of sera.Conclusion: 1. INFL treatment induces the occurrence of non transitory IFL ANA in all our patients, without differences both in titre and morphological pattern between RA and IBD-SA. 2. Anti DNAds are induced in a high proportion of patients. This phenomenon is not confined to RA, is probably due to non IgG antibodies (thus confirming previous reports), is transient and not related to relevant clinical events. A variety of autoantibodies, mainly related to nuclear minor specificities (anti DNAss, AHA, ANS) seldom appear for a short time during treatment. 3. Finally, INFL does not affect at all anti-CCP, thus confirming that, although related to a more aggressive RA form, they do not parallel the activity of the disease.Citation: , volume , supplement , year 2004, page Session: Rheumatoid arthritis – Clinical aspects