Predictive factors of rapidly progressive-interstitial lung disease in patients with clinically amyopathic dermatomyositis.

Clinically amyopathic dermatomyositis (CADM) is a unique subset of dermatomyositis, showing a high incidence of lung involvements. The aim of this study is to identify risk factors, other than melanoma differentiation-associated protein (MDA)-5, for developing rapidly progressive-interstitial lung disease (RP-ILD) in patients with CADM. Forty CADM patients, in whom 11 patients developed RP-ILD, were enrolled. Clinical features and laboratory findings were compared between the patients with and without RP-ILD. We found that skin ulceration, CRP, serum ferritin, anti-MDA5 Ab, and lymphocytopenia were significantly associated with ILD. Multivariate logistic regression analysis indicated that anti-MDA5 Ab(+), elevated CRP, and decreased counts of lymphocyte were independent risk factors for RP-ILD, which can provide a precise predict for RP-ILD in CADM patients. When anti-MDA5 Ab(+) was removed from the multivariate regression model, using skin ulcerations, elevated serum ferritin and decreased counts of lymphocyte can also precisely predict RP-ILD. Except for MDA-5, more commonly available clinical characteristics, such as skin ulcerations, serum ferritin, and count of lymphocyte may also help to predict prognosis in CADM.

Inhibition of osteoclast differentiation and matrix metalloproteinase production by CD4+CD25+ T cells in mice.

UNLABELLED: To reveal the mechanism of inflammation-accompanied osteoporosis, mouse CD11b cells and CD4+CD25+ T cells were cocultured. Our results showed that CD11b+ monocytes cocultured with CD4+CD25+ T cells generated significantly less osteoclasts than those cocultured with CD4+CD25- T cells. The levels of MMP-7 and 9 in coculture supernatant were decreased significantly when CD11b+ monocytes and CD4+CD25+ T cells were cocultured comparing to the CD4+CD25- T cell group. These results highlight the role of CD4+CD25+ T cells on rheumatic osteoporosis. INTRODUCTION: The purpose of this study was to reveal the mechanism of inflammation-accompanied osteoporosis by examining the effect of CD4+CD25+ T cells on osteoclast formation, as well as the production of matrix metalloproteinases (MMP)-2, 3, 7, and 9 from osteoclasts. METHODS: Mouse CD11b cells and CD4+CD25+ T cells were isolated using the microbead-based kits. Activated CD11b cells and CD4+CD25+ T were cocultured. CD4+CD25- T cells were used as controls. Osteoclasts were evaluated by counting the average of tartrate-resistant acid phosphatase-positive multinucleated large cells among five high-power fields (×200). After 2 days of coculture, supernatants were harvested for MMP measurement (by ELISA). RESULTS: At day 7, the CD11b+ monocytes cocultured with CD4+CD25+ T cells generated significantly (both p < 0.01) less osteoclasts (3.4 ± 0.8) than those cocultured with CD4+CD25- T cells (16.2 ± 1.3) and those cultured alone (16.2 ± 2.7). The supernatant levels of MMP-7 and 9 were decreased significantly (p < 0.01) when CD11b+ monocytes and CD4+CD25+ T cells were cocultured compared to the other two conditions. CONCLUSIONS: The decreased CD4+CD25+ T cells may cause an overproduction of MMP-7 and 9 from osteoclasts, which highlight the role of CD4+CD25+ T cells on rheumatic osteoporosis.

Increased CCR4 expression on circulating CD4(+) T cells in ankylosing spondylitis, rheumatoid arthritis and systemic lupus erythematosus.

Previous studies have suggested that CCR4 is particularly important in the selective recruitment of various subsets of leucocytes in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this study, we examined the percentage of CD4(+)/CCR4(+) T cells within circulating lymphocytes in active ankylosing spondylitis (AS), RA and SLE patients. The clinical significance of CCR4 expression as well as possible associations between the expression and serum levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 were also examined. Our results showed that the percentage of CD4(+)/CCR4(+) T cells was significantly elevated in AS and RA patients as compared with normal controls. The percentage was also significantly higher in SLE patients who had received no treatment with glucocorticoids or cytotoxic drugs (untreated SLE) than that in controls. In addition, the percentage of CD4(+)/CCR4(+) T cells showed significant positive correlations with the Bath ankylosing spondylitis disease activity index (BASDAI) in AS and with the SLE disease activity index (SLEDAI) in untreated SLE. Of all the cytokines examined, the elevated serum IL-10 level was closely correlated with the percentage of CD4(+)/CCR4(+) T cells in AS, RA and untreated SLE. These results suggest that CCR4 may be crucial in the pathogenesis of AS, RA and SLE. The percentage of CD4(+)/CCR4(+) T cells can serve as a useful marker for the activity of AS and untreated SLE.