Immune effects of miRNA and Th17 cells on ß-Lg allergy in dietary milk based on mouse model.

ß-lactoglobulin (ß-Lg) allergy in dietary milk seriously affects the use of high-quality milk protein in infants. In order to solve this problem, the expression of miRNA and Th17 cells in milk ß-Lg allergic reaction of children's diet was studied. METHOD: female BALB/c mice aged 5-6 weeks were selected as the subjects and randomly divided into blank group and ß-Lg sensitized group, with 10 mice in each group. On the 1st, 7th and 14th day, the mice in the ß-Lg sensitized group were intraperitoneally injected with allergen (Freund's adjuvant + ß-Lg). Mice in the blank group were given the same amount of normal saline. Blood samples were collected from the eyeballs of mice to determine the number of inflammatory cells. The contents of Th17 related cytokines and transcription factors in spleen were detected by RT-PCR. RESULTS: 1. the number of eosinophils and neutrophils in the ß-Lg sensitized group were 15.76/mL and 24.36/mL, respectively, which were significantly higher than those in the blank group (P < 0.05); 2. in the mice of ß-Lg sensitized group, the expression of miR-146a and miR-155 was abnormal, the number of Th17 cells was abnormally increased, and the expression levels of IL-17 and RORγt were significantly increased; 3. the abnormal expression of miR-146a and miR-155 in the mice of ß-Lg sensitized group was positively correlated with the secretion of Th17 related cytokines, which could be used as one of the biological indexes to evaluate allergic reaction. CONCLUSION: the number of Thl7 increased abnormally in dietary milk allergy patients. miRNA gene expression and IL-17 expression could be used as one of the biological indicators to evaluate the allergic reaction of ß-Lg.

Roles of macrophage migration inhibitory factor in polymyositis: Inflammation and regeneration.

Objective To elucidate the clinical significance of macrophage migration inhibitory factor (MIF) serum concentration in patients with polymyositis. Methods Thirty-six patients with polymyositis were enrolled. Serum samples were obtained and stored to detect MIF and interleukin (IL)-6 using commercially available enzyme-linked immunosorbent assay kits. The relationships between these cytokines and clinical data were analyzed. Results The serum MIF concentration was significantly lower in patients in remission (34.74 ± 17.75) and in healthy controls (38.87 ± 9.30 ng/ml) than that in patients with active polymyositis (50.04 ± 23.84 ng/ml). There were no significant differences between healthy controls and patients in remission. The serum IL-6 concentration in patients with active polymyositis (19.67 ± 7.16 pg/ml) was significantly higher than that in patients in remission (15.81 ± 4.00 pg/ml) and controls (8.14 ± 3.71 pg/ml). The serum IL-6 concentration was negatively correlated with the serum MIF concentration (r = -0.283). No relationship was found between the serum MIF concentration and glucocorticoid dose. The MIF concentration peaked twice during treatment when the creatine kinase concentration was decreasing. Conclusion MIF and IL-6 play important roles in the inflammation associated with polymyositis. MIF might also be involved in the early stage of regeneration in polymyositis. MIF may thus serve as a biomarker of disease activity and outcome.

The expression of death decoy receptor 3 was increased in the patients with primary Sjögren's syndrome.

Previous studies suggested a pathological role for the death decoy receptor 3 (DcR3) in systemic lupus erythematosus (SLE) and rheumatic arthritis (RA). Herein, the expression of DcR3 in primary Sjögren's syndrome (pSS) and the relationship with clinical characteristics were investigated. The serum DcR3 levels of pSS patients and healthy controls were measured by ELISA. Pearson's correlation analysis was used to evaluate the relationship between the DcR3 levels with the clinical characterstics of pSS patients. Additionally, the DcR3 expression in salivary glands of pSS patients was investigated by the immunohistochemistry method. The serum DcR3 expression in pSS patients was significantly higher than healthy controls (p < 0.001), especially in new onset pSS patients (p = 0.036). Moreover, Pearson's correlation analysis show that DcR3 levels were positively correlated with age (p = 0.013), platelet (PLT) (p = 0.002), hemoglobin (Hb) (p = 0.004), Sjögren's syndrome disease damage activity index (SSDAI) score (p = 0.005), Sjögren's syndrome disease damage index (SSDDI) score (p < 0.001) and EULAR Sjögren's syndrome disease activity index (ESSDAI) score (p = 0.010). Furthermore, the DcR3 levels were significantly lower when the pSS patients were treated with the disease-modifying anti-rheumatic drugs. At last, DcR3 expression in salivary glands of pSS patients was significantly higher than healthy controls. The DcR3 expression was significantly elevated in the pSS patients and positively correlated with the clinical characteristics, and it might be an important factor involved in the progression of pSS patients and could be a potential therapeutic target.

New insights into the role and mechanism of macrophage migration inhibitory factor in steroid-resistant patients with systemic lupus erythematosus.

INTRODUCTION: Glucocorticoid (GC) therapy remains important in improving the prognosis of patients with systemic lupus erythematosus (SLE). However, some patients do not achieve an effective response with GC treatment, creating an obstacle to the remission of SLE. Identification of the underlying mechanisms responsible for steroid resistance can be significant. Macrophage migration inhibitory factor (MIF) arouses our interest because of its reciprocal relationship with GCs. In the present study, we investigated for the first time whether MIF correlated with steroid resistance in SLE and explored potential mechanisms of action. METHODS: Sixty-two patients with SLE (40 steroid sensitive and 22 steroid resistant) and 21 normal controls were recruited. Serum levels of MIF were measured by ELISA. Cytosolic MIF and IκB expression in peripheral blood mononuclear cells (PBMCs) were determined by western blotting. The electrophoretic mobility shift assay was assessed by NF-κB in nuclear aliquots. Gene silencing was applied to reduce expression of MIF in PBMCs in steroid-resistant patients. PBMCs obtained from steroid-sensitive patients were treated with recombinant human MIF of different concentrations. RESULTS: MIF levels in serum and PBMCs were higher in steroid-resistant patients compared with steroid-sensitive patients and controls. In contrast to the steroid-sensitive group, NF-κB levels were significantly higher and IκB levels lower in steroid-resistant patients. After MIF gene silencing, IκB levels in cells from steroid-resistant patients were increased. In steroid-sensitive patients, a decrease in IκB levels and an increase in NF-κB expression from baseline were detected in PBMCs treated with a higher concentration of recombinant human MIF. Treatment with recombinant human MIF did not regulate expression of IκB and NF-κB in PBMCs from patients treated with an anti-MIF monoclonal antibody. CONCLUSIONS: Our results indicated that MIF may play a role in the formation of steroid resistance in SLE by affecting the NF-κB/IκB signaling cascade. As a regulator of glucocorticoid sensitivity, MIF may be a potential target for steroid sparing.

The clinical significance of HRCT in evaluation of patients with rheumatoid arthritis-associated interstitial lung disease: a report from China.

The objective of this study is to describe the interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients of China, and to study clinical significance of high-resolution computed tomography (HRCT) in evaluation and treatment. One hundred and ten Chinese patients (79 women and 31 man) diagnosed with RA between December 2008 to November 2009 were analyzed. According to the HRCT, 47 (42.73%) RA patients were diagnosed as ILD. Old age, smoking and pulmonary rales were closely related to ILD (P < 0.05). The main appearances of ILD were ground-glass (39.09%), honeycombing (4.55%), reticular patterns and consolidation (1.82%). Patients with reticular patterns and honeycombing were more likely to show the respiratory symptoms. It was also common to find other abnormal changes, such as fiber cord shadow (22.73%), lung markings fuzzy disorder (30%), pulmonary nodules (11.82%), emphysema (9.09%), bronchiectasis (3.64%), subpleural nodules (11.82%) and pleural thickening (24.55%). In treatment, honeycombing and subpleural nodules were more common in patients with methotrexate (MTX) and/or leflunomide treatment than without (P < 0.05). Other abnormal changes were no statistical significance (P > 0.05). Pulmonary involvement is common in RA patients, and it is suggested that HRCT could be a sensitive and useful way in evaluating the lung of RA patients.

Clinical features and prognosis of adult-onset still's disease: 61 cases from China.

OBJECTIVE: To describe the onset, clinical features, prognostic factors, and treatment of adult-onset Still's disease (AOSD) in cases from China. METHODS: Sixty-one Chinese patients with AOSD were analyzed retrospectively. RESULTS: Common clinical features were fever (100.0%), rash (88.5%), and arthritis (82.0%). The laboratory findings were as follows: leukocytosis (83.6%), increased erythrocyte sedimentation rate (100.0%), elevated transaminase concentrations (23.0%), elevated ferritin levels (79.6%), negative antinuclear antibody (88.5%), and negative rheumatoid factor (88.5%). Of the 61 patients, 44.3% exhibited a monocyclic disease pattern, 29.5% experienced disease relapse at least once, 16.4% exhibited chronic articular course, and 9.8% died; most deaths were due to pulmonary infection and respiratory failure. Based on the disease course, we divided the 61 patients into 2 groups: those with favorable outcome (cyclic disease course, n = 45) and unfavorable outcome (chronic disease course or death, n = 16). We analyzed the prognostic factors for the 2 groups, and found that pleuritis, interstitial pneumonia, elevated ferritin levels, and failure of fever to subside after 3 days of prednisolone at 1 mg/kg/day were unfavorable prognostic factors for patients with AOSD. CONCLUSION: Patients with AOSD had complex symptoms with no specific laboratory findings. Our results indicate that AOSD is not a relatively benign disease, especially in cases that are refractory to high doses of prednisone.

The levels of macrophage migration inhibitory factor as an indicator of disease activity and severity in adult-onset Still's disease.

OBJECTIVES: This study investigated the levels of macrophage migration inhibitory factor (MIF) in adult-onset Still's disease (AOSD) and explored the role of this pro-inflammatory cytokine in the systemic inflammation of AOSD. DESIGN AND METHODS: Serum MIF levels were measured by ELISA in patients with AOSD and controls. Intracellular MIF production by peripheral blood leukocytes was detected by three-color flow cytometry. RESULTS: Serum MIF levels were significantly increased in patients with AOSD. Serum MIF levels were significantly higher in AOSD patients with sore throat, myalgias, splenomegaly, or pleuritis, and were closely correlated with clinical disease severity and activity. Examined by flow cytometry, the intracellular MIF levels in monocytes and T-lymphocytes from AOSD patients were significantly higher than those from healthy subjects. CONCLUSION: These data represent the first demonstration of increased MIF expression in AOSD, and suggest that MIF may be an important marker for disease evaluation and monitoring.