Interleukin-6 and IgA-rheumatoid factor are crucial for baseline erosiveness, and anti-citrullinated peptide antibodies for radiographic progression in early rheumatoid arthritis treated according to a treat-to-target strategy.

OBJECTIVES: To define baseline clinical and immunological characteristics [anti-citrullinated peptide antibodies (ACPAs), immunoglobulin M (IgM)- and IgA-rheumatoid factor (RF), and interleukin-6 (IL-6) levels] involved in determining baseline erosiveness, outcome, and radiographic progression among seropositive and seronegative early rheumatoid arthritis (ERA) patients. METHOD: The 408 ERA patients enrolled in the study were monitored every 3 months according to the treat-to-target strategy. At baseline and after 12 months, hand and foot radiographs were evaluated using the Sharp/van der Heijde erosion score. RESULTS: At diagnosis, seronegative patients were older and had higher Disease Activity Scores (DASs) than seropositive patients. A higher risk of erosiveness at baseline was conferred by IgA-RF positivity and IL-6 plasma levels ≥7.6 pg/mL, particularly when simultaneously present. In multivariate analysis, disease duration and IL-6 plasma levels ≥7.6 pg/mL arose as independent variables associated with presence of erosions at onset. Radiographic progression at 1 year follow-up, which occurred in 11.1% of ERA patients, was predicted by ACPA positivity, together with higher age at diagnosis. Despite similar percentages of good European League Against Rheumatism response, DAS and Boolean remission being observed over time among seropositive and seronegative patients and between erosive and non-erosive subjects, ERA patients who were erosive at onset, IgA-RF seropositive, and simultaneously having high baseline IL-6 plasma levels (≥7.6 pg/mL) were treated to a greater extent with tumour necrosis factor blockers after 12 months. CONCLUSION: IgA-RF positivity and IL-6 plasma levels are crucial for baseline erosiveness, while ACPA positivity represents the strongest risk factor for developing radiographic progression in ERA.

Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells.

Acute inflammation is a complex and tightly regulated homeostatic process that includes leucocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as rheumatoid arthritis (RA), it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells, including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets.

Human milk as a vector and an indicator of exposure to PCBs and PBDEs: temporal trend of samples collected in Rome.

Thirty-seven polychlorobiphenyl (PCB) congeners and seven polybromodiphenylether (PBDE) congeners were measured in human milk samples collected in Rome between 2005 and 2007. The comparison of results with two previous studies performed in Rome in 1984 and in 2000-2001 indicates a 64% decrease of PCB levels, still in progress; profile differences with time were also evident as lighter congeners are less relevant now; data are in good agreement with recent European studies. PBDE contamination profiles were different in individual samples and a similar variability was observed in data from different countries, suggesting different exposure pathways and profiles.

[Italian consensus on the recommendations about the use of methotrexate for the treatment of rheumatic diseases with a focus on rheumatoid arthritis: results from the "3E initiative"]. / Consensus italiana sulle raccomandazioni per l'utilizzo del methotrexate nelle malattie reumatiche con focus sull'artrite reumatoide: i risultati della "3E initiative".

OBJECTIVE: To develop a set of national evidence-based recommendations for the use of Methotrexate (MTX) in daily clinical practice. METHODS: A panel of 37 Italian Rheumatologists reviewed 10 international recommendations formulated during the "3E (Evidence, Expertise, Exchange) initiative" for the year 2007-8, following a systematic literature search in Medline, Embase, Cochrane Library, and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts and the revision of selected papers and the appraisal of Oxford levels of evidence. Moreover, the same panel by the same methodology formulated further 5 recommendations on topics previously selected by Italian representatives to 3E initiative. The agreement about the set of proposed recommendations was stated by a consensus process and the potential impact on clinical practice was assessed. RESULTS: International Recommendations were analysed and changed when appropriate. In addition, 5 national recommendations were developed by identifying 6371 references, selecting and evaluating the 29 ones satisfying Evidence Based Medicine principles. CONCLUSIONS: A set of 15 national recommendations for the use of MTX in daily clinical practice was developed. These recommendations are evidence-based and integrate the expertise of a large panel of Italian rheumatologists.

Citrullination: the loss of tolerance and development of autoimmunity in rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial inflammation and pannus formation leading to destruction of cartilage and bone. Several self proteins have been suggested to be disease-driving autoantigens. Proteins are encoded by a limited number of genes in our genome. Post-translational modifications such as citrullination of the arginine residues, can increase the morphological and the functional diversity of the proteome. The positivity of anti-citrullinated peptides autoantibodies occurs then at an early stage of the disease development. Several factors, among which the synovial tissue inflammatory and the nitric oxide reaction, are involved in the regulation of the citrullination reaction. All of them have to be analysed and considered to understand the loss of tolerance and the development of autoimmunity leading to the disease.