Eleonora Bruschi

Autoantibodies to heterogeneous nuclear ribonucleoproteins.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are among the most abundant proteins in the eukaryotic cell nucleus and play a direct role in several aspects of the RNA life including splicing, export of the mature RNAs and translation. To date, ∼30 proteins have been identified. A growing body of evidence points to hnRNPs as an important target of the autoimmune response in rheumatic diseases. Autoantibodies to A and B proteins of the hnRNP complex have been detected in late 1980s in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Beyond their role as diagnostic test in clinical practice, these autoantibodies are starting to be regarded as important tools to obtain deeper insight into the pathogenesis of autoimmune rheumatic diseases. Furthermore, new anti-hnRNP antibodies have been recognized in the last ten years extending the spectrum of anti-hnRNP reactivity in different autoimmune disorders.

Safety of Abatacept in Rheumatoid Arthritis With Serologic Evidence of Past or Present Hepatitis B Virus Infection

Rheumatoid arthritis (RA) with concomitant hepatitis B virus (HBV) infection represents a therapeutic challenge due to the risk of HBV reactivation under immunosuppressive treatment. To date there are few data coming from anecdotal case reports that concern HBV reactivation following treatment with abatacept. This observational retrospective study was aimed to assess the safety profile of abatacept in this particular clinical setting.

Reduced dose of tocilizumab for the maintenance of remission in patients with rheumatoid arthritis: a clinical experience

disease activity after dose reduction regained low disease activity after returning to the standard dose. The study by van Herwaarden et al. paved the way for further investigation on the effectiveness of reduced-dose TCZ in clinical practice. At our center, we conducted a small pilot, descriptive-only observation in ten RA patients who were under therapy with standard-dose TCZ from at least 12 months and in clinical remission from at least 6 months. After informed consent, TCZ therapy was reduced to 4 mg/kg. Each month, at the infusion visit, patients were monitored using approved clinical scales (VAS, HAQ, CDAI, and SDAI) and by ultrasound (US) examination, which is increasingly used in the determination of disease progression [5]. One patient developed a neoplasia and was then excluded from the analysis. Two patients experienced reactivation of disease, 2 and 4 months since the initiation of reduced-dose TCZ, respectively; standard-dose TCZ therapy was then reinstituted, and clinical remission was observed at the following visit in both patients. We report here the data reported at 12 months after the initiation of reduced-dose TCZ, in the remaining seven patients. Overall, at the end of the observation period, all patients showed stable disease remission, although a minor worsening in all scales was observed (mean DAS28-VES: 1.7 ± 1.1 at baseline vs. 2.4 ± 1.2 at 12 months; DAS28-PCR: 1.5 ± 0.8 vs. 2.2 ± 0.5; HAQ: 0.1 ± 0.4 vs. 0.2 ± 0.4; CDAI: 3.1 ± 2.9 vs. 4.7 ± 2.8; SDAI: 3.2 ± 2.9 vs. 4.8 ± 2.8). Disease remission was also confirmed at US (number of joints with articular effusion: 4.0 ± 2.5 vs. 5.7 ± 4.1; number of joints with synovial hypertrophy: 4.7 ± 2.8 vs. 6.6 ± 4.4; number of positive joints at Power Doppler: 0.7 ± 1.0 vs. 0.6 ± 0.8). Although the preliminary and descriptive-only nature of our pilot analysis does not allow to retrieve any definite conclusion, our findings lend further support to the Tocilizumab (TCZ) is a humanized monoclonal interleukin-6 (IL-6) receptor antibody which has demonstrated clinical efficacy in the treatment of patients with moderate–severe rheumatoid arthritis (RA) who experienced inadequate response to methotrexate and one or more antiTNFα agent [1, 2]. The efficacy of TCZ in the treatment of RA is supported by a bulk of evidence which includes randomized clinical trials and observational, ‘field-practice’ studies [2]. TCZ can be administered intravenously at the standard dose of 8 mg/kg either in combination with other disease-modifying antirheumatic drugs (DMARDs) or as a monotherapy [2]. The favorable efficacy and tolerability profile of TCZ is sustained over a long term (up to 9 years) [2]. Although the above-mentioned evidence supports the use of TCZ in clinical practice, additional data are required to fully explore the optimal individualization of this treatment for each single patient [3]. For instance, it has been recently suggested that some of patients on TCZ achieve low disease activity with a lower than registered starting dose, i.e., 4 mg/kg [4]. In a retrospective study by van Herwaarden et al. [4] on 22 RA patients treated with TCZ 8 mg/kg for about 6 months and tapered to 4 mg/kg because of low disease activity, 55 % of patients remain in disease remission at 6 months since the reduction in dose; however, a slight increase in the disease activity score 28 (DAS28) was observed at the end of the observation period. Interestingly, all patients with worsened

Clinical and Serological Response to Tocilizumab in Patients with Rheumatoid Arthritis

Objective: The role of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the response to treatment for rheumatoid arthritis (RA) such as tocilizumab (TCZ) is still not completely understood. This study investigates the relationship between the presence and levels of RF and anti-CCP and clinical response to TCZ in patients with RA. Methods: This was an observational longitudinal study in 27 patients with active, long-standing RA despite previous treatment with >2 Disease-Modifying Anti Rheumatic Drugs (DMARDs) and/or steroids. Patients were treated with TCZ 8 mg/kg every 4 weeks. The following parameters were assessed: Erythro Sedimentation Rate (ESR), C - reactive protein (CRP), Health Assessment Questionnaire (HAQ), Disease Activity Score of 28 joints (DAS28), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). IgM-, IgA- and IgGRFs and anti-CCP antibodies were measured using ELISA at baseline, 3 months (T1), 6 months (T2), and 12 months (T3). Results: All patients showed significant and sustained clinical response to TCZ treatment. All clinical scales with the exception of HAQ significantly decreased. There was a significant correlation (p=0.03) between anti-CCP and SDAI changes from baseline at T1 and T2. However, no significant correlation was measured between antibody count at T0 and changes in the DAS-28 ESR at T1 and at T2. Also, there was no correlation between clinical scales and antibody levels RF-IgG, IgA, IgM as well as between clinical scales and anti-CCP levels. Conclusions: Tocilizumab is effective in treating the clinical symptoms of RA, and the efficacy of this molecule was not correlated with either RF or anti-CCP levels.