Autoantibodies profile of rheumatoid arthritis patients during treatment with infliximab

Abstract

Purpose: Therapy with TNFα blocking agents has been associated with increased rate of anti-nuclear antibodies (ANA) and rare cases of lupus like syndromes. Our aim was to prospectively analyze a wide array of autoantibodies in rheumatoid arthritis (RA) patients before and 14 weeks after starting infliximab.Material and Methods: In this study, 26 consecutive active RA patients participated. All treated with infliximab at a dosage of 3 mg/kg on week 0, 2, 6 and every 8 weeks, along with weekly low dose methotrexate. Patients were evaluated at week 0 and 14. Clinical assessment included the number of tender and swollen joints, duration of morning stiffness, adverse events (AE) (including SLE-like) and ESR. Sera were collected before the 1st infusion of infliximab at week 0 and 14. The autoantibodies studied were: fluorescent ANA, anti-double-stranded-DNA (anti-ds-DNA), IgG and IgM anti-cardiolipin (ACA), anti-histone- H1 and C (H1, H2A, H2B, H3, H4), anti-SSA, -SSB, -ENA, -scleroderma 70, -thyroid peroxidase (TPO) and -neutrophilic cytoplasmatic (ANCA) antibodies.Results: Of 26 patients, 17 were women. A significant decrease in duration of morning stiffness, number of tender and swollen joints and ESR were observed between week 0 and 14. During follow up (mean of 20.5±7.3 months), 9 patients stopped infliximab due to inefficacy or AE (most of them after the 4th infusion). Two patients developed lupus-like phenomena. ANA was found positive at baseline in 7 out of 26 patients. In 5 of them, an increase in the titer of ANA was observed at week 14. ANA negative turned positive for 8 patients. A significant increase of anti-cardiolipin (ACA)-IgM levels was observed in 8 patients and of ACA-IgG in 6, in parallel with ANA seroconversion. The mean level of anti-double-stranded-DNA (anti-ds-DNA) -IgG significantly increased from 66±33 to 93±68 IU/ml, in 4 patients to pathological levels. Four patients demonstrated an increase in anti-histone H1. Levels of ANCA, anti-ENA, -SSA, -SSB, -RNP, -scleroderma70 and -thyroid peroxidase (TPO) were negative in all patients and remained unchanged during the study. Cessation of treatment with infliximab was found to be associated with the appearance of ANA.Conclusion: An increased titer or a new appearance of ANA was observed in 12 out of 26 patients. The main autoantibodies found were anti-ds-DNA, ACA-IgM and -IgG and anti-histone. In our cohort, the appearance of some autoantibodies seemed to predict late cessation of treatment.