乾癬における抗カルパスタチン抗体の測定

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1740号 , 学位授与年月日 : 平成18年3月22日, 学位授与大学 : 金沢大

BAFF antagonist attenuates the development of skin fibrosis in Tight-Skin Mice

The tight-skin (TSK/+) mouse, a genetic model for systemic sclerosis (SSc), develops cutaneous fibrosis and autoimmunity. Although immunological abnormalities have been demonstrated in TSK/+ mice, the roles of B-cell-activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, have not been investigated. Serum BAFF levels in TSK/+ mice were examined by ELISA. Newborn TSK/+ mice were treated with BAFF antagonist, and then skin fibrosis of 8-week-old mice was assessed. Serum BAFF levels were significantly elevated in TSK/+ mice. Remarkably, BAFF antagonist inhibited the development of skin fibrosis, hyper-γ-globulinemia, and the autoantibody production in TSK/+ mice. The skin from TSK/+ mice showed upregulated expressions of fibrogenic cytokines, such as IL-6 and IL-10, while BAFF antagonist significantly suppressed them. Reciprocally, BAFF antagonist augmented antifibrogenic cytokines, such as IFN-γ, in the skin of TSK/+ mice. Furthermore, TSK/+ B cells with BAFF stimulation had a significantly enhanced ability to produce IL-6. The results suggest that BAFF/BAFF receptor system is critical for the development of skin fibrosis in TSK/+ mice and could be a potent therapeutical target. © 2007 The Society for Investigative Dermatology

Elevated Serum BAFF Levels in Patients with Localized Scleroderma in contrast to other organ-specific autoimmune diseases

Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma. © 2007 The Authors Journal compilation © 2007 Blackwell Munksgaard

Active elbow flexion is possible in C4 quadriplegia using hybrid assistive limb (HAL®) technology: A case study

<p><b>Context</b>: Patients with complete quadriplegia after high cervical spinal cord injury are fully dependent with activities of daily living. Assistive technology can improve their quality of life. We examined the use of a hybrid assistive limb for single joints (HAL-SJ) in a 19-year-old man with complete C4 quadriplegia due to chronic spinal cord injury to restore function of active elbow flexion. This is the first report on the use of the HAL-SJ in a patient with spinal cord injury.</p> <p><b>Findings</b>: The HAL-SJ intervention for each elbow was administered in 10 sessions. Clinical assessment using surface EMG was conducted to evaluate muscle activity of the trapezius, biceps brachii, infraspinatus, and triceps brachii muscle before, and during the 2nd, 3rd, 6th, and 9th interventions. Surface electromyography (EMG) before intervention showed no contraction in the upper arms, but in the bilateral trapezius. The HAL-SJ used motion intention from the right trapezius for activation. After the 6th and 7th session, respectively, biceps EMG showed that voluntary contraction and right elbow flexion could be performed by motion intention from the right biceps. After the 10th session, voluntary bicep contraction was possible. HAL-SJ treatment on the left elbow was performed using the same protocol with a similar outcome. After completing treatment on both upper extremities, both biceps contracted voluntarily, and he could operate a standard wheelchair for a short distance independently.</p> <p><b>Conclusion</b>: HAL-SJ intervention is feasible and effective in restoring elbow flexor function in a patient with C4 chronic spinal cord injury and complete quadriplegia.</p

E- and P-Selectins Synergistically Inhibit Bleomycin-Induced Pulmonary Fibrosis

The development of bleomycin-induced lung injury, which is a model of pulmonary fibrosis, results from inflammatory cell infiltration, a process highly regulated by the expression of multiple adhesion molecules. Therefore, bleomycin-induced lung fibrosis was examined in E-selectin(−/−) mice, P-selectin(−/−) mice, and E-selectin(−/−) mice treated with anti-P-selectin monoclonal antibody (mAb) in comparison of wild-type mice. E-selectin(−/−) mice treated with anti-P-selectin mAb exhibited augmented lung fibrosis histologically, increased lung collagen deposition, and increased mortality compared to wild-type mice. Furthermore, lung interferon-γ mRNA expression decreased in E-selectin(−/−) mice treated with anti-P-selectin mAb relative to wild-type mice, while tumor necrosis factor-α and interleukin-6 mRNA expression increased in these mice. Similar changes were observed in E-selectin(−/−) mice, albeit to a lesser extent than those treated with anti-P-selectin mAb. Remarkably, flow cytometric analysis revealed that the frequency of interferon-γ-producing natural killer T (NKT) cells in the bronchoalveolar lavage was decreased in E-selectin(−/−) mice and E-selectin(−/−) mice treated with anti-P-selectin mAb compared with wild-type mice. Moreover, the majority of NKT cells expressed high levels of CXCR3, suggesting that NKT cell infiltration is also dependent on CXCR3 expression. These results suggest that E- and P-selectins synergistically inhibit lung fibrosis by promoting the recruitment of NKT cells