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ObjectivesTo collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis.MethodsFifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians.ResultsThe study population comprised 26 males and 24 females aged 0–61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment.ConclusionsIn patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.

Objective This prospective study aimed to determine whether the comprehensive ultrasonographic assessment of synovial inflammation predicts relapse after discontinuation of treatment with a biologic agent in patients with rheumatoid arthritis (RA) in clinical remission. Methods RA patients in clinical remission (Disease Activity Score in 28 joints [DAS28]

Introduction. This study aimed to investigate the efficacy of abatacept for arthritis in patients with rhupus, an overlap syndrome between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods. Patients who fulfilled both the 2010 ACR/EULAR criteria for RA classification and the 1997 ACR revised criteria for classification of SLE and received abatacept treatment for arthritis were retrospectively studied. Results. Six rhupus patients who fulfilled the inclusion criteria above were identified. All patients had active arthritis despite receiving antirheumatic drugs including methotrexate when abatacept was initiated. Clinical Disease Activity Index (CDAI) significantly decreased between baseline and 12 weeks (P = 0.028) and remained low through 24 weeks. All patients achieved either a good or moderate response according to the EULAR response criteria at 24 weeks. Health Assessment Questionnaire-Disability Index (HAQ-DI) also significantly decreased between baseline and 24 weeks (P = 0.043). In addition, the levels of immunoglobulin G and anti-DNA antibody significantly decreased between baseline and 24 weeks (P = 0.028 and P = 0.043, resp.). Conclusions. Treatment with abatacept is likely to be efficacious in patients with rhupus whose arthritis is refractory to methotrexate. In addition, abatacept may have a moderate effect on abnormal antibody production in rhupus patients.

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease and proinflammatory cytokines such as TNFα and IL-6 play critical roles in the pathogenesis of RA. The blockade of IL-6 signaling by Tocilizumab (TCZ) has shown the clinical efficacy for patients with RA. To clarify the roles of IL-6 signaling in CD4+ T cells in the pathogenesis of RA, we previously compared gene expression profiles of CD4+ T cells by DNA microarray analysis before and after the treatment with TCZ in RA patients who exhibited good clinical responses to the treatment (1, 2), and identified that B cell leukemia/lymphoma 3 (Bcl3), an IκB family member, was down-regulated by TCZ therapy (1). However, the role of Bcl3 expressed in CD4+ T cells in the pathogenesis of RA remains unclear. Objectives The objective of this study is to examine the role of Bcl3 expressed in CD4+ T cells in the pathogenesis of RA. Methods We compared signal intensity of Bcl3 in CD4+ T cells between untreated RA patients and healthy controls by DNA microarray analysis. We examined the roles of IL-6-STAT3 signaling in Bcl3 induction. We also analyzed gene expression profiles of Bcl3-transduced CD4+ T cells by RNA-sequencing analysis. We examined the effect of enforced expression as well as gene silencing of Bcl3 on the development of T follicular helper (Tfh) cells. Finally, we examined a correlation between signal intensities of Bcl3 and Tfh cell-related genes in CD4+ T cells in untreated RA patients. Results Bcl3 levels were significantly higher in RA patients than those in healthy controls. IL-6 induced Bcl3 expression in CD4+ T cells in a STAT3-dependent manner. Transcriptome analysis revealed that the expression of Bcl6, a master regulator of Tfh cell differentiation, was significantly upregulated by the enforced Bcl3 expression ([Figure1][1]). The enforced Bcl3 expression increased but the Bcl3 silencing decreased IL-21-producing Tfh-like cells. Bcl3 levels were positively correlated with those of Tfh cell-related genes such as CXCR5, ICOS, and ASCL2 in CD4+ T cells in RA patients. ![Figure][2] Conclusions Bcl3 is involved in the development of Tfh cells and the pathogenesis of RA presumably by inducing IL-21 production. References 1. Saito Y, Kagami SI, Sanayama Y, Ikeda K, Suto A, Kashiwakuma D, et al. AT-rich interactive domain-containing protein 5a functions as a negative regulator of RORγt-induced Th17 cell differentiation. Arthritis Rheum. 2014;66(5):1185-94. 2. Sanayama Y, Ikeda K, Saito Y, Kagami S, Yamagata M, Furuta S, et al. Prediction of therapeutic responses to tocilizumab in patients with rheumatoid arthritis: biomarkers identified by analysis of gene expression in peripheral blood mononuclear cells using genome-wide DNA microarray. Arthritis Rheum. 2014;66(6):1241-31. Disclosure of Interest K. Meguro: None declared, K. Suzuki: None declared, J. Hosokawa: None declared, Y. Sanayama: None declared, S. Tanaka: None declared, S. Furuta: None declared, K. Ikeda: None declared, H. Takatori: None declared, A. Suto: None declared, O. Ohara: None declared, H. Nakajima Grant/research support from: Chugai Pharmaceutical Co., Ltd, Bristol-Myers Squibb, and Mitsubishi Tanabe Pharma Co. [1]: #F1 [2]: pending:yes

A 1/2.5 inch, 5.2 Mpeixel CMOS image sensor with wide dynamic range operation mode is developed and its effectiveness for high contrast scene pictures is verified. The adopted algorithm for this operation is inherently free from fixed pattern noise generation which often resists the realization of mass production level wide dynamic range image sensors. The attained dynamic range is 96 dB with 12 bit output scheme.

Background Clinical information does not accurately predict relapse after discontinuation of biological agents in patients with rheumatoid arthritis (RA). Although ultrasound is a sensitive tool to detect sub-clinical synovial inflammation in RA patients with low disease activity, the ultrasound findings on the unilateral hand did not discriminate between patients who relapsed and who did not after discontinuation of TNF antagonists in the previous report 1 . Objectives This pilot, single-blinded, prospective study aimed to determine whether the comprehensive ultrasound scan on 40 joints is informative in the prediction of relapse after discontinuation of biological agents. Methods RA patients in remission states (DAS28 ≤ 2.6) receiving biological agents who agreed to discontinue the biological agent were recruited. Patients underwent a comprehensive ultrasound scan on 40 joints (DAS28 joints + ankles + MTP joints) and were prospectively followed up for 26 weeks. The physicians who evaluated the patients during the study period were blinded to the ultrasound findings at baseline. Results Thirty patients receiving either TNF antagonists (n = 24), or tocilizumab (n = 6) were enrolled. The disease activity was very low (median DAS28 1.64 [IQR 1.2-2.3]) before the biological agent was discontinued. Eleven patients had relapse which was defined as DAS28 > 3.2 and restarted receiving the same biological agent within 26 weeks. Total ultrasound scores provided with larger areas under the ROC curves for the prediction of relapse than DAS28 did. Using the optimal cut-off values determined by the ROC analysis, the PPV and NPV of total GS score ≥ 12 to predict flare were 88% and 82%, respectively. On the other hand, the PPV and NPV of total PD score ≥ 3 were 100% and 79%, respectively. Image/graph Conclusions In RA patients with very low disease activity receiving biological agents, a comprehensive ultrasound scan provides good diagnostic values to predict relapse after discontinuation of the biological agent. References Saleem B, Keen H, Goeb V, Parmar R, Nizam S, Hensor EM, et al. Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped? Ann Rheum Dis 2010;69(9):1636-42. Disclosure of Interest T. Iwamoto: None Declared, K. Ikeda Grant/research support from: Mitsubishi-Tanabe Pharma Corporation, Abbott Japan Co., Ltd, Consultant for: Mitsubishi-Tanabe Pharma Corporation, Abbott Japan Co., Ltd, J. Hosokawa: None Declared, M. Yamagata: None Declared, S. Tanaka: None Declared, Y. Sanayama: None Declared, D. Nakagomi: None Declared, A. Okubo: None Declared, K. Takahashi: None Declared, K. Hirose: None Declared, M. Sueishi: None Declared, H. Nakajima Grant/research support from: Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd, Consultant for: Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd

Introduction In addition to the pivotal roles of mast cells in allergic diseases, recent data suggest that mast cells play crucial roles in a variety of autoimmune responses. However, their roles in the pathogenesis of autoimmune skeletal muscle diseases have not been clarified despite their distribution in skeletal muscle. Therefore, the objective of this study is to determine the roles of mast cells in the development of autoimmune skeletal muscle diseases. Methods The number of mast cells in the affected muscle was examined in patients with dermatomyositis (DM) or polymyositis (PM). The susceptibility of mast cell-deficient WBB6F1-KitW/KitWv mice (W/Wv mice) to a murine model of polymyositis, C protein-induced myositis (CIM), was compared with that of wild-type (WT) mice. The effect of mast cell reconstitution with bone marrow-derived mast cells (BMMCs) on the susceptibility of W/Wv mice to CIM was also evaluated. Results The number of mast cells in the affected muscle increased in patients with PM as compared with patients with DM. W/Wv mice exhibited significantly reduced disease incidence and histological scores of CIM as compared with WT mice. The number of CD8+ T cells and macrophages in the skeletal muscles of CIM decreased in W/Wv mice compared with WT mice. Engraftment of BMMCs restored the incidence and histological scores of CIM in W/Wv mice. Vascular permeability in the skeletal muscle was elevated in WT mice but not in W/Wv mice upon CIM induction. Conclusion Mast cells are involved in the pathogenesis of inflammatory myopathy.