IL-17 is overproduced by T cells from the peripheral blood and fibrotic lesions of the skin and lungs in SSc patients. These results suggest that IL-17 overproduction plays an important role in the pathogenesis of SSc, especially in the early stages of the disease, by inducing the proliferation of fibroblasts and the production of IL-1 and the expression of adhesion molecules on endothelial cells.

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The lubrication mechanism between the human flexor digitorum profundus tendon and the A2 pulley was investigated in vitro. The gliding resistance at the interface between the tendon and the pulley increased significantly after the tendon had been treated with a hyaluronidase solution. Alcian-blue staining of the surface of the tendon before and after it was treated with hyaluronidase suggested the presence of hyaluronate complex. Alcian blue-positive and hyaluronidase-sensitive materials, such as hyaluronate or proteoglycan, in the synovial membrane and the matrix of the tendon, may act as a boundary lubricant, facilitating the gliding and reducing the resistance between the tendon and the pulley.

Objective. The aim of this prospective multicenter study was to identify biomarkers that can be used to predict therapeutic responses to tocilizumab in patients with rheumatoid arthritis (RA).Methods. We recruited patients with RA who were treated with tocilizumab for the first time, and determined therapeutic responses at 6 months. In the training cohort (n ‫؍‬ 40), gene expression in peripheral blood mononuclear cells (PBMCs) at baseline was analyzed using genome-wide DNA microarray, with 41,000 probes derived from 19,416 genes. In the validation cohort (n ‫؍‬ 20), expression levels of the candidate genes in PBMCs at baseline were determined using real-time quantitative polymerase chain reaction (qPCR) analysis.Results. We identified 68 DNA microarray probes that showed significant differences in signal intensity between nonresponders and responders in the training cohort. Nineteen putative genes were selected, and a significant correlation between the DNA microarray signal intensity and the qPCR relative expression was confirmed in 15 genes. In the validation cohort, a significant difference in relative expression between nonresponders and responders was reproduced for 3 type I interferon response genes (IFI6, MX2, and OASL) and MT1G. Receiver operating characteristic curve analysis of models incorporating these genes showed that the maximum area under the curve was 0.947 in predicting a moderate or good response to tocilizumab in the validation cohort.Conclusion. Using genome-wide DNA microarray analyses, we identified candidate biomarkers that can be used to predict therapeutic responses to tocilizumab in patients with RA. These findings suggest that type I interferon signaling and metallothioneins are involved in the pathophysiology of RA.Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, which

Interstitial pneumonitis (IP) is the most frequent and serious pulmonary involvement in patients with dermatomyositis (DM)/polymyositis (PM) [1][2][3][4][5][6][7][8]. In one study representing the largest series of autopsy cases with DM/PM, the mean survival of patients with IP was shown to reduce to only 8 months after the onset of pulmonary symptoms [5]. We also showed that IP developed in 32% of 111 DM/PM patients and that 35% of DM/PM patients with IP died of respiratory failure in a year [8]. Moreover, it has been shown that 44-60% of IP in DM/PM, especially in DM, is resistant to high-dose corticosteroid therapy and the corticosteroid-resistant IP patients die of respiratory failure in a relatively short period [6][7][8]. Furthermore, we and others have recently shown that the corticosteroid-resistant IP is successfully treated with a T cell-specific immunosuppressant cyclosporin [8][9][10], suggesting that the activation of T cells is importantly involved in the development of corticosteroid-resistant IP in DM/PM. Therefore, in order to determine the difference in T cell activation states between corticosteroid-resistant and corticosteroidsensitive IP in DM/PM, we studied the activation markers and cytokine profiles of T cells in bronchoalveolar lavage fluids (BALF) from patients with IP in DM/PM before prednisolone therapy and then compared the activation states of T cells according to the therapeutic response of IP to prednisolone therapy. Our results indicate that activated Th1-type pulmonary T cells are importantly involved in the development of corticosteroidresistant IP in DM/PM and that the increase in CD25 + CD8 + T cells in BALF is a useful indicator for corticosteroid-resistant IP in DM/PM. 541 Activation of pulmonary T cells in corticosteroid- SUMMARYTo study the activation states and cytokine profiles of pulmonary T cells in corticosteroid-resistant and corticosteroid-sensitive interstitial pneumonitis (IP) in dermatomyositis (DM)/polymyositis (PM), we examined the activation markers and cytokine profiles of T cells in bronchoalveolar lavage fluids (BALF) from patients with IP in DM/PM before prednisolone therapy and then compared the activation states of T cells according to the therapeutic response of IP to prednisolone therapy. CD25 + CD4+ T cells in BALF were significantly increased in both corticosteroid-resistant and corticosteroidsensitive IP in DM/PM as compared with those in controls without IP. Furthermore, CD25 + CD4 + T cells in BALF were significantly more increased in corticosteroid-resistant IP than those in cortico teroidsensitive IP. Moreover, CD25+ CD8