GM-CSF Increases Mucosal and Systemic Immunogenicity of an H1N1 Influenza DNA Vaccine Administered into the Epidermis of Non-Human Primates

Background: The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a worldwide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99) HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun) was analyzed in rhesus macaques. Methodology/Principal Findings: Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particlemediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI) antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine. Conclusions/Significance: These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skindelivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract. © 2010 Loudon et al

The use of musculoskeletal ultrasound in a Rheumatology Outpatient Clinic.

INTRODUCTION: Musculoskeletal ultrasound (US) represents a valid, reliable and sensitive-to-change tool for the evaluation of patients suffering from rheumatic conditions. This method demonstrates a wide applicability and availability, finding place in the clinical practice in rheumatology outpatient clinic. AIM: To perform an epidemiological evaluation related to the use of US in a university rheumatology outpatient clinic. MATERIAL AND METHODS: During a 3-month period, data concerning consecutive patients attending to the US Unit of Department of Rheumatology, Sapienza University of Rome were registered. We collected the demographic data, the diagnosis, the reason for the US examination, the examined joints, as well as the requesting physicians' specialty. RESULTS: In the period October-December 2013, 572 patients (M/F 137/435; mean age+/-SD 55.2+/-15.8 years) were registered. The US examination was more frequently requested for the following diseases: rheumatoid arthritis (29.5%), osteoarthritis (10.6%), spondyloarthritis (9.1%), and connective tissue diseases (8.9%). In 239 of cases (41.8%), the US evaluation was requested for other indications. The US evaluation was requested slightly more frequently for monitoring (55.7%) compared to diagnosis (44.3%). The requesting physician was a rheumatologist in the majority of the cases (80.6%). The most frequent requested were the hand joints (28.9%) and wrists (23.3%). CONCLUSIONS: US examinations are most frequently used in the evaluation of patients with rheumatoid arthritis and mainly to monitor the disease. The exam is requested mostly by rheumatologists. The hand joints and wrists were the most frequently evaluated

Immunoglobulin A antibodies to oxidized collagen type II as a potential biomarker for the stratification of spondyloarthritis from rheumatoid arthritis

Objectives The discovery of diseased tissue-specific neoantigens offers the opportunity to develop important disease tissue-specific biomarkers that can help in the prediction, diagnosis, and stratification of diseases. This opportunity is specifically significant for autoimmune diseases where diagnostic biomarkers are not available. Inflammatory autoimmune diseases are commonly associated with local generation of large amounts of reactive oxidants. We have previously identified oxidative post-translationally modified (oxPTM) tissue-specific neoantigens in rheumatoid arthritis (RA) and type 1 diabetes that elicit an immune response. In the current study, we studied the presence and clinical significance of antibodies to oxPTM collagen type II (CII) in patients with spondyloarthritis (SpA). Method Levels of antibodies specific to native CII and oxPTM-CII were assessed by enzyme-linked immunosorbent assay. Results Immunoglobulin G (IgG) binding to oxPTM-CII was observed in 52%, 83%, and 28% of serum samples from patients with axial spondyloarthritis (axSpA), RA, and psoriatic arthritis (PsA), respectively. Importantly, while strong IgA anti-oxPTM-CII responses were detected in axSpA and PsA patients, with 47% and 84% respective binders, no IgA anti-oxPTM-CII was detected in RA patients. IgA anti-oxPTM-CII reactivity in axSpA patients treated with biologics was higher and more frequent, with 85% binders compared to 9% binders in patients treated with synthetic disease-modifying anti-rheumatic drugs. Conclusion Our data imply that SpA and PsA are associated with the presence of antibodies to oxPTM-CII, suggesting that there may be a humoral component that may distinguish patients with SpA from RA. Our approach could be adapted to other diseases, particularly to inflammatory autoimmune diseases.</p