Tomoyuki Imagawa

MR imaging of murine arthritis using ultrasmall superparamagnetic iron oxide particles

The objective of this work was to determine the ability of magnetic resonance (MR) imaging with ultrasmall superparamagnetic iron oxide (USPIO) particles to provide quantitative measures of inflammation in autoimmune arthritis. Mice were injected intravenously or intra-articularly with USPIO followed by magnetic resonance and histological assessment of the knee joint. Comparisons were made between MR microimages and histology in naïve mice and mice with collagen-induced arthritis.Following intravenous administration, accumulation of USPIO was observed in the popliteal lymph nodes, but not the joint. Administration of USPIO intra-articularly resulted in signal loss in the joint. The MR signal intensity could be quantified and correlated with iron staining in the synovial lining. A marked increase in USPIO uptake and a corresponding decrease in signal intensity were observed in arthritic, compared to naïve mice. Areas of focal signal loss corresponded to foci of iron staining by histology. These studies may provide a basis for the clinical application of USPIO in arthritis for assessing disease severity and monitoring response to therapy.

Expression of angiogenic factors in juvenile rheumatoid arthritis: Correlation with revascularization of human synovium engrafted into SCID mice

OBJECTIVE Although increased vascularity was noted in early histopathologic studies of juvenile rheumatoid arthritis (JRA) synovium, the available data on angiogenesis in JRA are very limited. The main purposes of this study were to assess expression of the key angiogenic factors in JRA synovium, and to evaluate a SCID mouse model of JRA as an approach to study in vivo regulation of the expression of these factors in JRA. METHODS RNase protection assay was used to assess the expression of the key angiogenic factors in fresh JRA synovium and in JRA synovial tissue fragments that had been minced and then implanted into SCID mice. Vascularity of the samples was assessed by immunohistochemical staining for von Willebrand factor. Synovial specimens obtained from patients with osteoarthritis (OA) or other noninflammatory arthropathies were used as controls. RESULTS Detectable levels of messenger RNA for vascular endothelial growth factor and angiopoietin 1 and their respective receptors, as well as endoglin and thrombin receptors, were present in all JRA tissue specimens studied. The levels of expression of these factors in JRA tissues were significantly higher than those in tissues obtained from patients with OA or other noninflammatory arthropathies. Furthermore, increased expression of the key angiogenic factors in the fresh JRA tissues correlated with the exuberant revascularization of JRA minced tissue fragments implanted into SCID mice. This was in sharp contrast to the poor revascularization of implanted OA tissues. CONCLUSION JRA synovium is characterized by high angiogenic activity. SCID mouse-human JRA synovium chimeras may provide a good approach to study the in vivo regulation of angiogenesis in JRA.

A111‐a: Setting Up of Japanese Online Registry of Pediatric Rheumatic Disease

Performing quality clinical and translational research in pediatric rheumatic diseases (eg. Juvenile Idiopathic Arthritis (JIA), Child onset Systemic Lupus Erythematosus (cSLE) and Juvenile Dermatomyositis (JDM)) had been difficult due the rarity of these diseases.

457. Fibronectin Peptide Reduces the Immune Response to Adenovirus and Enhances Transgene Expression

Adenovirus is a well-known vector for delivering therapeutic genes to tissues. However, it induces an immune response against viral antigens, which results in loss of transgene expression. This has limited the utility of adenovirus in applications in which long-term transgene expression is desired. Fibronectin (FN) is an extracellular matrix glycoprotein that interacts with a variety of cells through integrin and non-integrin receptors. These interactions play a role in cell adhesion and migration during an inflammatory response. In previous studies, we showed that a 33-KD carboxyl-terminal heparin-binding fragment of fibronection (FN-C/H-II) inhibited leukocyte recruitment in mouse arthritis. The present study was designed to determine whether FN-C/H-II could also blunt the inflammatory response to adenovirus. An adenoviral vector (1 × 109 particles) encoding murine IL-10 (AdmIL10) was co-injected with an equal titer of either an adenovirus encoding FN-C/H-II (AdFN) or a control backbone adenovirus (AdBglII) into knee joints of normal C57BL/6 mice. Expression of mIL-10 was significantly higher in the knees co-injected with AdFN over a 2 week observation period. Histological evaluation revealed a marked reduction in infiltration of both neutrophils and lymphocytes in the synovium of mice co-injected with the AdFN vector. These results suggest that adenoviral expression of FN-C/H-II peptide can reduce adenovirus-associated inflammation and enhance the efficacy of adenovirus as a gene transfer vector.