Search

Background Patient9s global assessment (PtGA) is one of the most widely used patient reported outcomes in rheumatoid arthritis (RA) that reflects both disease activity and other factors. PtGA is onymous and obtained at hospital, which may cause a conscious or unconscious bias, whereas PtGA obtained anonymously may be free from any bias. The credibility of PtGA to report RA patient outcomes has been usually investigated by assessing test-retest reliability. There has been no study comparing routine PtGA and PtGA where patients answered anonymously. Objectives The aim of this study was to compare routinely obtained in-hospital PtGA before clinical examination with those answered anonymously at home. Additionally, physician9s global assessment (PhyGA) was compared with routine PtGA and anonymized PtGA Methods We asked RA patients (n=389) to answer and mail the PtGA test anonymously, Clinical data regarding disease duration, stage, class, swollen joint counts, tender joint counts, pain visual analog scale (VAS), PhyGA, Health Assessment Questionnaire (HAQ), EuroQOL five dimensions questionnaire (EQ5D), Kessler 6 scale (anxiety/ depression), treatment data, laboratory data, and socioeconomic factors were collected simultaneously. We compared the PtGA that is routinely surveyed at hospital before clinical examination with those surveyed anonymously at home. We calculated a discrepancy score by subtracting anonymized PtGA from routine in-hospital PtGA. We defined (1) positive discrepancy when routine PtGA was over-rated relative to the anonymized PtGA; (2) negative discrepancy when routine in-hospital PtGA was under-rated relative to the anonymized PtGA. Results The anonymized PtGA score was higher than routinely evaluated in-hospital PtGA (p Conclusions Discrepancy exists between routine in-hospital PtGA and anonymized PtGA. The high pain VAS scale and low QOL are risk factors that could make the difference between routine PtGA from anonymized PtGA. There is a possibility that high pain VAS score and low QOL influence the reliability of PtGA. Disclosure of Interest None declared

Background Osteoporosis is one of the important adverse effects in the glucocorticoids treatment for the patients with rheumatoid arthritis (RA) and connective tissue diseases (CTDs). Although the usefulness of denosmab for primary osteoporosis has been well-established, the efficacy for GIOP remains unclear. Objectives This study aimed to clarify the therapeutic effects of denosumab for GIOP. Methods We evaluated bone mineral density (BMD) and serum markers of bone metabolism (BAP, NTx, TRACP-5b and P1NP) of patients who had been treated with over 5mg of predonisolone for RA and CTDs, and denosumab for GIOP, for two years in Kobe University Hospital. BMD and serum markers were evaluated every six months for 2 years from the baseline. The changes of those data from baseline were analyzed by Student9s t test using GraphPad Prism 5 software and p Results Number of the patients were 53 (male: 4 cases, female: 49 cases), and their characteristics at the beginning of denosumab treatment were as below; age: 64.19±12.0 years old, dose of prednisolon: 10.59±9.97mg/day, BMD of lumber spine: 0.768±0.112g/cm3, T-score of lumber spine: -2.28±1.01, BMD of femoral neck: 0.540±0.085g/cm3, T-score of femoral neck: -2.28±0.76. After 2-years denosumab treatment, T-scores of lumber spine (0.54±0.39 gain) and femoral neck (0.13±0.26 gain) were significantly increased from baseline (Figure; mean ± SEM. *:p Conclusions Denosumab can suppress bone metabolic turnover, and increase lumber spine and femoral neck T-scores of GIOP patients. Disclosure of Interest None declared

Background Behcet9s disease is a systemic vasculitis disease with oral and genital aphthous ulcers, ocular involvements, skin manifestations, arthritis, gastrointestinal manifestations, neurogenic diseases and vascular involvements. Patients with Behcet9s disease are known to distribute along the ancient Silk Road, including Japan. Objectives We evaluate the clinical features of Behcet9s disease in Japan. Methods We retrospectively investigated 223 patients (108 males and 115 females) who fulfilled the International Criteria for Behcet9s Disease (ICBD) from January, 2006 until May, 2015.We examined sex, onset age, disease type, clinical symptoms, laboratory data and medications. Results Median age at diagnosis was 36.0±12.8 years old. Oral ulcers were the most common manifestation (98.2%), followed by genital ulcers (62.4%), ocular involvements (53.2%), erythema nodosum (53.2%), acneiform lesions (51.8%), arthritis (38.6%), gastrointestinal manifestations (25.1%), neurogenic diseases (9.0%), and vascular involvements (8.1%). The relationship of HLA and disease manifestations was studied in 123 patients (41.5% with HLA-B51 and 24.1% with HLA-A26). The frequency of acneiform lesions, ocular involvements and HLA-B51 was significantly higher in male, while genital ulcers and arthritis were significantly higher in female. Patients with ocular involvements showed a higher assosiation rate with neurogenic diseases and HLA-B51, and lower wih gastrointestinal manifestations. TNFα inhibitor (infliximab or adalimumab) were used for 66 cases (30%), and it could be continued for 1 year in 91%, and for 2 years in 83%. Conclusions A higher incidence of gastrointestinal manifestations was observed in patients with Behcet9s disease in Japan. Patients with ocular involvements showed a higher assosiation rate with neurogenic diseases, and lower wih gastrointestinal manifestation. Most patients could continue TNFα inhibitor safety and effectively. Disclosure of Interest None declared

Background Many signaling pathways activated under inflammatory and hypoxic conditions have profound effects on intracellular metabolism to support cell growth and survival. The recent findings of cancer-specific metabolic changes, including increased glucose and glutamine consumption, has provided new therapeutic targets for consideration. The microenvironment in inflamed joints in RA is also characterized by hypoxia and low concentration of nutrients, and fibroblast-like synoviocytes from RA patients (RA-FLS) is known to have several tumor-like characteristics. However, the role of glucose and glutamine metabolism in the aberrant proliferation of these cells is unclear. Objectives We evaluated the role of these metabolic pathways in RA-FLS proliferation and in autoimmune arthritis in SKG mice. Methods The expression of glycolysis- or glutaminolysis-related enzymes was evaluated by real-time PCR and Western blotting, and the intracellular metabolites were evaluated by metabolomic analyses. The effects of glucose or glutamine on RA-FLS cell growth were investigated using glucose- or glutamine-free medium. Glutaminase 1 (GLS1) siRNA and the GLS1 inhibitor compound 968 were used to inhibit GLS1 in RA-FLS. Arthritis was induced in SKG mice by zymosan A injection. Compound 968 was used to study the effect of GLS1 inhibition on Zymosan A-injected SKG mice. Ki-67-positive cells were analyzed by immunohistochemistry. Results GLS1 expression was increased in RA-FLS, and metabolomic analyses revealed that glutamine and glutamate consumption were increased in RA-FLS. RA-FLS proliferation was reduced under glutamine-deprived, but not glucose-deprived conditions. Cell growth of RA-FLS was inhibited by GLS1 siRNA transfection or GLS1 inhibitor treatment. Silencing of GLS1 in RA-FLS did not affect IL-6 or MMP-3 production in supernatants. GLS1 expression in RA-FLS was not affected by pro-inflammatory cytokine stimulation. Compound 968 ameliorated the autoimmune arthritis and decreased the number of Ki-67-positive synovial cells in SKG mice. Conclusions Our findings suggested that glutamine metabolism plays an important role in regulating RA-FLS proliferation, without being affected by pro-inflammatory cytokine stimulation or affecting cytokine production, and may be a novel therapeutic target for RA. Disclosure of Interest None declared

Background SKG mice develop interstitial lung disease (ILD) resembling human rheumatoid arthritis (RA)–associated ILD. We identified a unique cell population of CD11b + Gr1 dim cells in the severely inflamed lungs in SKG mice. Objectives The aims of this study are to clarify the mechanism behind the lung pathology, and to elucidate the phenotype and function of CD11b + Gr1 dim cells in ILD-induced SKG mice. Methods We assessed the severity of zymosan A-induced ILD in SKG mice histologically, and examined lung-infiltrating cells by Giemsa stain and flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (M-MDSCs) were cultured in vitro with GM-CSF (and IL-4). The proliferation of CSFE-labeled naive T cells co-cultured with isolated CD11b + Gr1 dim cells and MDSCs was evaluated by flow cytometry. Results MDSCs, Th17 cells, and group 1 and 3 innate lymphoid cells (ILC1s and ILC3s) were increased in the lungs; the proportion of these cells varied with ILD severity. In this process, we found that a unique cell population, CD11b + Gr1 dim cells, were expanded in the severely inflamed lungs (Figure). About half of the CD11b + Gr1 dim cells expressed CD11c and Giemsa stain revealed that they were morphologically dendritic cell (DC)-like. The CD11b + Gr1 dim cells were induced from M-MDSCs with GM-CSF in vitro and were considered tolerogenic because they expressed high levels of PD-L1 and suppressed T-cell proliferation. The CD11b + Gr1 dim cells have never described previously and termed CD11b + Gr1 dim tolerogenic DC-like cells (CD11b + Gr1 dim tolDC-LCs). Th17 cells, ILC1s and ILC3s in the inflamed lung produced GM-CSF, which in turn could induce CD11b + Gr1 dim tolDC-LCs to reduce inflammation. Conclusions We identified a unique cell population, termed CD11b + Gr1 dim tolDC-LCs, in ILD-induced lungs in SKG mice. References Nishimura K, Saegusa J, Matsuki F, Akashi K, Kageyama G, Morinobu A. Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates arthritis in SKG mice. Arthritis Rheumatol 2015;67:893–902. Shiomi A, Usui T, Ishikawa Y, Shimuzu M, Murakami K, Mimori T. GM-CSF but not IL-17 is critical for the development of severe interstitial lung disease in SKG mice. J. Immunol 2014;193:849–59. Takenaka MC, Quintana FJ. Tolerogenic dendritic cells. Semin. Immunopahol 2016. doi:10.1007/s00281–016–0587–8. Acknowledgements The authors thank Shino Tanaka (Department Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine) for providing technical assistance. Disclosure of Interest None declared