Expansion of exhausted CD8+ T cells associates with increased pulmonary fungal infection risk in anti-melanoma differentiation associated gene 5 dermatomyositis.

OBJECTIVES: Anti-MDA5+ dermatomyositis was associated with poor prognosis due to the high incidence of rapid progressive interstitial lung disease, pulmonary infection. The aim of this study is to investigate the abundance and clinical relevance of exhaustion markers on peripheral CD8 T cells from patients with idiopathic inflammatory myopathy (IIM). METHODS: Twenty-nine healthy controls (HCs) and 71 patients with IIM were enrolled, including 42 with anti-MDA5+ and 18 with anti-MDA5- dermatomyositis (DM) and 11 with anti-synthetase syndrome (ASS). Flow cytometry was applied to detect PD-1, TIM-3 and LAG-3 in CD8 T cells. The clinical associations of the CD8 T cell exhaustion phenotype in patients with anti-MDA5+ DM were analysed. RESULTS: CD8 T cells from patients with anti-MDA5+ DM showed significantly increased LAG-3, TIM-3 and PD-1 compared to those from patients with anti-MDA5- IIM (18 with anti-MDA5- DM and 11 with ASS) or HCs (adjusted p all < 0.05). CD8 T cells with distinct exhaustion levels were all significantly increased in anti-MDA5+ DM patients compared with HCs (p all < 0.05). Patients with high level of PD-1+ TIM-3+LAG-3+ CD8+ T cells had a significant higher incidence of pulmonary fungal infections but lower counts of CD4+ and CD8+ T cells. ROC analysis revealed that the frequency of PD-1+TIM-3+LAG-3+CD8+ T cell significantly predicted pulmonary fungal infections (area under the curve: 0.828). CONCLUSIONS: CD8 T cells from patients with anti-MDA5+ DM show significant exhausted phenotype, and increased exhausted CD8 T cells were associated with high risk of pulmonary fungal infection.

Clinical characteristics of anti-isoleucyl-tRNA synthetase antibody associated syndrome and comparison with different patient cohorts.

OBJECTIVES: This study aimed to analyse the clinical features of anti-isoleucyl-tRNA synthetase (OJ) antibodies in Chinese patients and to compare with previously published cohorts. We reviewed the clinical data of anti-OJ antibody positive patients, including their long-term follow-up. RESULTS: Anti-OJ antibodies were present in 10 of 1269 (0.8%) patients with idiopathic inflammatory myopathies (IIMs), and 10/320 (3.1%) patients with anti-synthetase syndrome (ASS). Of the anti-OJ antibody-positive patients, 90% had interstitial lung disease (ILD), of whom three (30%) developed rapidly progressive ILD (RP-ILD). Half (50%) of the patients were febrile and developed myocardial involvement; 40% of patients experienced myositis, mechanic's hands and arthritis. Compared to the anti-Jo-1 group, the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the anti-OJ antibody-positive group were higher (p<0.05). From a review of the literature regarding the clinical features of anti-OJ, fever was more common in the eastern cohort (41.7% vs. 8.3%, p=0.002), whereas patients in western countries were more likely to develop arthritis (20.9% vs. 58.1%, p=0.001). With complete follow-up of the present cohort, 80% improved with treatment, including one patient who underwent lung transplant. CONCLUSIONS: The anti-OJ antibody occurred infrequently in Chinese patients, ILD was the major clinical feature, but myocardial injury was also a prominent associated complication. Anti-OJ positive patients were responsive to treatment.

Infection is not rare in patients with idiopathic inflammatory myopathies.

OBJECTIVES: To assess the prevalence and characteristics of infections in patients with idiopathic inflammatory myopathies (IIM) and analyse risk factors for infection using clinical presentation and biochemical findings of IIM. METHODS: Retrospective review of the medical records of patients with IIM followed up in a single medical centre from January 2008 to January 2018. RESULTS: Of the 779 patients with IIM, 215 (27.6%) suffered from infections. The prevalence of infection in dermatomyositis (DM) (29.8%) was more than polymyositis (PM) (18.5%). The lung was the most common infection site (66.5%). Multivariate analyses demonstrated that methylprednisolone pulse (MP) (OR=3.22; 95% CI=1.60 - 6.48; p=0.001), age of onset >50 years (OR=1.02; 95% CI=1.00 - 1.03; p=0.011), anti-melanoma differentiation-associated gene 5 (MDA5) antibody (OR=1.93; 95% CI=1.20 - 3.11; p=0.007), lymphocyte count <1200/mm3 (OR=2.85; 95% CI=1.89 - 4.30; p<0.001), and interstitial lung diseases (ILD) (OR=2.03; 95% CI=1.30 - 3.71; p=0.002) are independent risk factors for infection. Survival analysis demonstrated that the three-year survival rate in the infection group was lower than the no-infection group (75.3% vs. 94.7%, p < 0.001). CONCLUSIONS: Among hospitalised individuals with IIM, infection is frequent and the leading cause of mortality. The anti-MDA5 antibody, lymphopenia, ILD, old age, and treatment with MP are contributing factors in the development of infections in patients with IIM.

Identification of a novel autoantibody against heat shock factor 1 in idiopathic inflammatory myopathy.

OBJECTIVES: Myositis autoantibodies show great utility in the diagnosis and clinico-serological phenotyping of idiopathic inflammatory myopathy (IIM). We identified a novel autoantibody against heat shock factor 1 (HSF1) and further evaluated its disease specificity and clinical significance in IIM patients. METHODS: A human protein microarray was used to identify autoantibodies in myositis sera. ELISA, immunoblot and dot blot assays were applied to examine anti-HSF1 autoantibodies in IIM patients and controls. Immunofluorescence was used to detect HSF1 expression in muscle tissues. RESULTS: Anti-HSF1 was identified as a novel autoantibody by protein microarray and the seroreactivity was confirmed by immunoprecipitation, ELISA, immunoblot and dot blot assays. Anti-HSF1 autoantibodies were present in 64/581 (11.0%) IIM, 4/37 (10.8%) rheumatoid arthritis, 5/40 (12.5%) primary Sjögren's syndrome, 2/40 (5%) systemic lupus erythematosus, while largely negative in healthy controls. Anti-HSF1 autoantibodies were significantly associated with pruritus, hypergammaglobulinaemia, and elevated erythrocyte sedimentation rate in IIM patients. Anti-HSF1 autoantibodies were more prevalent in cancer-associated myositis (CAM) compared to non-CAM patients (17.2% vs. 7.5%, p=0.009), nevertheless were undetectable in cancer controls. Meanwhile, cross-sectional and longitudinal analyses revealed positive correlations between anti-HSF1 levels and disease activity in IIM patients without cancer. Additionally, increased expression of HSF1 was found in regenerating muscle cells of myositis muscle tissues. CONCLUSIONS: These data reveal anti-HSF1 as a new autoantibody associated with CAM in IIM. The autoimmunity against HSF1 may be involved in the immunopathogenesis of myositis.

[Influence of Ciprofloxacin on the Microbial Community and Antibiotics Resistance Genes in a Membrane Bioreactor].

A membrane bioreactor (MBR) was used to treat ciprofloxacin (CIP)-contaminated artificial wastewater. The microbial community structure and the abundance of antibiotic resistant genes (ARGs) in the MBR were studied at four CIP dosages (0, 5 mg·L-1, 10 mg·L-1, and 15 mg·L-1). The results showed that Proteobacteria and Bacteroidetes remained the dominant phylum, with relative abundances of 57.5% and 12.7%, respectively, as the dosage of CIP was increased from 0 mg·L-1 to 15 mg·L-1. Rhodocyclaceae, Chitinophagaceae, and Comamonadaceae became the dominant family with abundances of 29.96%, 5.44%, and 6.60%, respectively. Methyloversatilis, Ferruginibacter, Zoogloea, and Comamonas became the dominant genus, with relative abundances of 21.70%, 7.56%, 5.24%, and 4.15%, respectively. The decrease of Chao1, ACE, and Shannon and the increase of Simpson indicated a decrease in microbial abundance and diversity. The relative abundances of Nitrosomonas, Nitrospira, Alcaligenes, and Nitrobacter decreased, which caused a decrease in the NH3-N removal rate. A CIP-ARGs analysis revealed that the relative abundances of gyrA, gyrB, and parC were increased, beginning after the sludge was dosed with 5 mg·L-1of CIP for 33 days, which augmented the risk for microbial drug-resistance.

[Removal and Influence of Ciprofloxacin in a Membrane Bioreactor].

A membrane bioreactor (MBR) was used to treat ciprofloxacin (CIP)-contaminated artificial wastewater. The pollutant removal performance and the microbial community structure of the MBR were studied at three different CIP dosages (0 mg·L-1, 5 mg·L-1, and 10 mg·L-1). The results showed that the sludge concentration in the reactor decreased and then levelled off as the dosage of CIP was increased from 0 mg·L-1 to 5 mg·L-1 and further to 10 mg·L-1. The mean removal of TOC and COD decreased from 98.40% and 97.80% to 84.20% and 94.10%, respectively, indicating that the CIP negatively influenced the organic removal but the effect was minor. In contrast, the ammonium removal was greatly influenced by the dosage of CIP. When the CIP dosage increased from 0 mg·L-1 to 5 mg·L-1 and further to 10 mg·L-1, the ammonium removal efficiency decreased from 96.91% to 84.14% and then to 77.80%, and the activity of Nitrosomonas, Alcaligenes, Nitrospira, and Nitrobacter were greatly inhibited. The CIP removal initially increased and then decreased. The mass balance revealed that the removal of CIP in the MBR was principally attributed to biodegradation and sludge adsorption, which accounted for 30.13% and 0.25%, respectively, at a CIP dosage of 5 mg·L-1 and 7.55% and 1.81% at a CIP dosage of 10 mg·L-1.

The prevalence and clinical significance of anti-PUF60 antibodies in patients with idiopathic inflammatory myopathy.

Autoantibodies against poly-U-binding factor 60 kDa protein (PUF60) have been reported in Caucasian dermatomyositis (DM) patients. However, their clinical significance in idiopathic inflammatory myopathy (IIM) remains to be fully clarified. Our objective was to analyze the prevalence and clinical significance of anti-PUF60 antibodies in a large cohort of Chinese IIM patients. In our study, 388 IIM patients, 301 disease controls, and 167 healthy controls (HCs) were involved. An enzyme-linked immunosorbent assay (ELISA) was developed to detect serum anti-PUF60 levels and was validated using immunoblotting methods. Unpaired Mann-Whitney U test and Spearman correlation analysis were used when appropriate. Anti-PUF60 antibodies were observed in IIM patients at a frequency of 10.6% (41/388). Subgrouping analysis revealed that the prevalence of anti-PUF60 antibodies was 10% in DM, 5.5% in polymyositis (PM), 10% in immune-mediated necrotizing myositis (IMNM), and 26.5% in myositis-overlap syndrome. Anti-PUF60 antibodies were also observed in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS) patients at a positive rate of 17.3, 14.5, and 10.1% respectively. Intriguingly, anti-PUF60 antibodies were frequently observed in clinically amyopathic dermatomyositis (CADM) patients and DM patients without currently known myositis autoantibodies. Furthermore, DM patients with anti-PUF60 antibodies had higher prevalence of skin ulcerations. Moreover, longitudinal investigation in eight DM patients with anti-PUF60 antibodies revealed that the antibodies levels decreased with disease remission. Anti-PUF60 antibodies were nonspecific for myositis, since they could be detected in other rheumatic diseases. Further investigation of anti-PUF60 antibodies may reveal shared pathogenic pathways in systemic autoimmune disorders.

A simple method for removing low-density granulocytes to purify T lymphocytes from peripheral blood mononuclear cells.

OBJECTIVE: Low-density granulocytes (LDGs) can form neutrophil extracellular traps (NETs) spontaneously and excessively. When peripheral blood mononuclear cells (PBMCs) are used for studying T lymphocytes, LDGs contained in the PBMCs may decrease the threshold of activating T lymphocytes by forming NETs. This study focused on the profiles of LDGs in common autoimmune diseases and methods for removing LDGs from PBMCs. METHODS: The percentages of LDGs in PBMCs from 55 patients with dermatomyositis (DM), 15 with polymyositis (PM), 42 with rheumatoid arthritis (RA), 25 with systemic lupus erythematosus (SLE), and 19 healthy controls were determined by flow cytometry. Three methods of removing LDGs were explored and compared. After removal, PBMCs from six patients with positive T-SPOT.TB were tested again to find out if LDGs contained in the PBMCs could influence T lymphocyte reactions. RESULTS: Significantly higher LDG percentages were found in PBMCs from patients with DM ((8.41±10.87)%, P<0.0001), PM ((8.41±10.39)%, P<0.0001), RA ((4.05±6.97)%, P=0.0249), and SLE ((7.53±11.52)%, P=0.0006), compared with the controls ((1.28±0.73)%). The T-SPOT.TB values significantly decreased after LDGs were removed. Increasing relative centrifugal force (RCF) within a limited range can decrease the LDG percentage from an initial high level, but not markedly increase the LDG clearance rate. Compared with the whole blood sediment method, the PBMC adherence method can significantly remove LDGs yet scarcely influence the T lymphocyte percentage in PBMCs. CONCLUSIONS: The LDG percentage in PBMCs is significantly increased in patients with SLE, DM, PM, and RA. The influence of LDGs on T lymphocytes cannot be ignored in PBMC cultures. The adherence method is a simple and easy-to-use method for removing LDGs and purifying T lymphocytes from PBMCs.

Transcriptomic profiling of long non-coding RNAs in dermatomyositis by microarray analysis.

Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome and have been found to be of functional importance. However, the potential roles of lncRNAs in dermatomyositis (DM) remain unknown. In this study, a lncRNA + mRNA microarray analysis was performed to profile lncRNAs and mRNAs from 15 treatment-naive DM patients and 5 healthy controls. We revealed a total of 1198 lncRNAs (322 up-regulated and 876 down-regulated) and 1213 mRNAs (665 up-regulated and 548 down-regulated) were significantly differentially expressed in DM patients compared with the healthy controls (fold change>2, P < 0.05). Subgrouping DM patients according to the presence of interstitial lung disease and anti-Jo-1 antibody revealed different expression patterns of the lncRNAs. Pathway and gene ontology analysis for the differentially expressed mRNAs confirmed that type 1 interferon signaling was the most significantly dysregulated pathway in all DM subgroups. In addition, distinct pathways that uniquely associated with DM subgroup were also identified. Bioinformatics prediction suggested that linc-DGCR6-1 may be a lncRNA that regulates type 1 interferon-inducible gene USP18, which was found highly expressed in the perifascicular areas of the muscle fibers of DM patients. Our findings provide an overview of aberrantly expressed lncRNAs in DM muscle and further broaden the understanding of DM pathogenesis.

[Removal of AOX and Chroma in Biologically Treated Effluent of Chemical Dyestuff Wastewater with Nanoscale Ni/Fe].

Nanoscale Ni/Fe was applied to biologically treated effluent of chemical dyestuff wastewater. The removal rates of absorbable organic halogens (AOX) and chroma were investigated at different Ni loadings (0-5%), initial wastewater pH (4.1-10.0), Ni/Fe dosage (1-5 g x L(-1)) and reaction time (0.5-96 h). The results showed that the removal rates of AOX and chroma firstly increased and then decreased with the increase of the Ni loading, while continuously increased with the decrease of the initial wastewater pH and the increase of Ni/Fe dosage. The optimal condition was Ni loading of 1%, initial wastewater pH of 4.1 and Ni/Fe dosage of 3 g x L(-1), under which 29.2% of AOX and 79.6% of chroma were removed after 24 h reaction, and 50.6% of AOX and 80.7% of chroma were removed after 96 h reaction. GC-MS analysis revealed that toxicants such as chlorinated anilines, p-nitroaniline, 4-methoxy-2-nitroaniline and halogenated hydrocarbons were efficiently removed.

[Removal of AOX, Chroma and TOC in Chemical Dyestuff Wastewater with Iron Scraps-Fenton-Coagulation Combined Process].

Iron scraps-Fenton-coagulation process was applied to chemical dyestuff wastewater. The removal performance of absorbable organic halogens(AOX), chroma and total organic carbon (TOC) was investigated at different molar ratios of Fe2+ to H2O2 (1:3-1:15), iron scraps reaction time (2-5 h) and Fenton reaction time (20-80 min). The results showed that the removal ratios of AOX, chroma and TOC firstly increased and then decreased with the decrease of the molar ratio of Fe2+ to H2O2, while continuously increased with the increase of iron scraps and Fenton reaction time. The optimal condition was determined as Fe2+:H2O2 ratio of 1:8, iron scraps reaction time of 4 h and Fenton reaction time of 60 min, under which 94.2% of AOX, 93.7% of chroma and 27.2% of TOC were removed. A comparison study revealed that the iron scraps-Fenton-coagulation combined process could achieve much better removal of AOX, chroma and TOC than any other single or combined processes of iron treatment, Fenton oxidation and coagulation. GC-MS analysis revealed that halogenated compounds and anilines were efficiently removed, as well as nitrobenzenes, phenols, benzaldehydes, ethers, nitriles and heterocyclic compounds.·OH was found to devote much in the Fenton reaction according to the tert-butyl alcohol trapping hydroxyl radicals test.

Ginsenoside Rg1 relieves tert-Butyl hydroperoxide-induced cell impairment in mouse microglial BV2 cells.

Microglial activation plays an important role in neurodegenerative diseases associated with oxidative stress. tert-Butyl hydroperoxide (t-BHP), an analog of hydroperoxide, mimics the oxidative damage to microglial cells. It has been reported that ginsenoside Rg1 (G-Rg1), an active ingredient of Panax ginseng, has anti-stress and anti-inflammatory properties. The present study aims to investigate the ability of G-Rg1 to decrease the t-BHP-mediated cell damage of BV2 microglial cells. We performed flow cytometry assays to facilitate the detection of reactive oxygen species as well as Western blotting analyses and immunofluorescence assays using specific antibodies, such as antibodies against phospho-mitogen-activated protein kinases (p-MAPKs), phospho-nuclear factor-κB (p-NF-κB), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), Caspase-3, autophagy marker light chain 3 (LC3), and Becline-1. We found that treatment with 50 µM G-Rg1 protected microglial cells against oxidative damage induced by 10 µM t-BHP.

Elevated Serum Levels of Soluble CD163 in Polymyositis and Dermatomyositis: Associated with Macrophage Infiltration in Muscle Tissue.

OBJECTIVE: To investigate serum levels of soluble CD163 (sCD163) in patients with polymyositis (PM) and dermatomyositis (DM), and to correlate these to clinical manifestations and laboratory data. METHODS: Serum levels of sCD163 were detected in 24 patients with PM, 84 patients with DM, and 46 healthy controls by using the ELISA method. Immunohistochemistry staining of macrophage infiltration in muscle tissue using anti-CD163 monoclonal antibody was conducted on muscle biopsy specimens from 13 patients with PM and 17 with DM. RESULTS: Serum levels of sCD163 were significantly increased in patients compared with healthy controls (p < 0.001). Patients with interstitial lung disease (ILD) had statistically higher sCD163 levels than patients without ILD (p < 0.001). High serum sCD163 levels were associated with increased incidence of antinuclear antibody (p < 0.05), higher serum levels of immunoglobulin G (p < 0.01) and immunoglobulin A (p < 0.05), and increased erythrocyte sedimentation rates (p < 0.01). Serum sCD163 levels were inversely correlated with CD3+ T cell counts in peripheral blood of patients (r = -0.306, p < 0.01). Cross-sectional assessment and longitudinal study revealed a significant correlation between serum sCD163 levels and disease activity. Patients with high serum sCD163 levels showed a higher incidence of CD163+ macrophage infiltration in muscle tissue than patients with normal sCD163 levels (chi-square value = 10.804, p < 0.01). CONCLUSION: Serum levels of sCD163 were significantly elevated and correlated with disease severity in patients with PM/DM, suggesting serum sCD163 as a promising biomarker in the disease evaluation of PM/DM. Our finding of elevated serum sCD163 levels associated with muscle macrophage infiltration highlights the role activated macrophage plays in the pathogenesis of PM/DM.

[AOX Pollution in Wastewater Treatment Process of Dyeing and Dyestuff Chemical Industries].

Selecting six large-scale dyeing factories and four large-scale dyestuff chemical factories in the well-developed Yangtze River Delta region, this study aimed to investigate the AOX pollution status in the raw wastewater as well as in the activated sludge treatment system. The components of AOX were characterized by GC-MS. Results showed that AOX concentration was low in wastewater from the six dyeing enterprises, ranging 0. 15-1. 62 mg.L-1 in the raw wastewater and 0. 06-1. 30 mg.L-1 in the biologically treated effluent. All the biologically treated effluent met the emission limits of 8 mg.L-1 in the Discharge Standard of Water Pollutants for Dyeing and Finishing of Textile Industry. Sludge in five factories with AOX was below 621 mg.kg-1, only one factory was with high AOX concentration of 3 280 mg.kg-1. By comparison, AOX concentration greatly varied between the wastewater from dyestuff chemical factories, was 1. 70 mg.L-1 to 78. 72 mg.L-1 in the raw wastewater and was 1. 88 mg.L-1 to 33. 11 mg.L-1 in the biologically treated effluent. AOX concentration in the activated sludge was as high as 960-2,297 mg.kg-1. Chlorobenzenes, chloronitrobenzenes, chloroanilines, chlorine nitroanilines and halophenols were typical TOX components detectable in the dyestuff chemical wastewater. Halophenols and chlorine nitroanilines could be efficiently removed. Single chloroanilines and single chloronitrobenzenes seemed to be easier removable than polychlorinated anilines and polychlorinated nitrobenzenes. Polychlorinated benzenes were also easily removal but the products chlorobenzene was hard to remove.

B-cell activating factor as a serological biomarker for polymyositis and dermatomyositis.

AIM: To investigate serum levels of B-cell activating factor (BAFF) in the patients with polymyositis (PM) and dermatomyositis (DM), and to systematically examine the association between serum BAFF levels and disease activity in PM/DM patients. PATIENTS & METHODS: A cross-sectional analysis included 92 PM/DM patients and 25 healthy control subjects. A longitudinal study followed 24 patients. Serum BAFF concentrations were detected by the ELISA method. RESULTS: Serum BAFF levels in PM/DM patients were significantly higher than those in healthy controls. A cross-sectional assessment revealed a modest correlation between serum BAFF levels and global disease activity and a mild correlation between serum BAFF levels and muscle disease activity. The longitudinal study showed that serum BAFF levels modestly correlated with global disease activity and muscle disease activity. CONCLUSION: Resulting data showed high serum BAFF levels in PM/DM patients and suggested BAFF as a serological biomarker for PM/DM disease activity.

Expression of tumor necrosis factor-like weak inducer of apoptosis and fibroblast growth factor-inducible 14 in patients with polymyositis and dermatomyositis.

INTRODUCTION: The aim of this study was to investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) in patients with polymyositis (PM) and dermatomyositis (DM), and their relation to clinical manifestations. METHODS: Serum levels of TWEAK were detected in 98 PM/DM patients and 37 healthy controls by using the ELISA method. Total RNA isolated from fresh-frozen muscle tissue samples of 36 PM/DM patients and 10 healthy controls were used for analyzing the mRNA levels of TWEAK and Fn14 by quantitative reverse transcription polymerase chain reaction (RT-PCR). Immunofluorescence staining of TWEAK and Fn14 was conducted on muscle biopsy specimens from 23 PM/DM patients and seven healthy controls. RESULTS: Serum levels of TWEAK were significantly decreased in the PM/DM patients compared to those in the healthy controls (P < 0.001), and serum TWEAK levels negatively correlated with serum CD163 levels in PM/DM patients (r = -0.49, P < 0.001). The expression of Fn14 mRNA was significantly increased in the muscle tissue of PM/DM patients than in the muscle tissue of healthy controls (P < 0.01), whereas the expression of TWEAK mRNA in PM/DM patients was not statistically different from that of the healthy controls (P > 0.05). Fn14 mRNA levels in muscle tissue positively correlated with muscle disease activity (r = 0.512, P < 0.01). Patients with oropharyngeal dysphagia had significantly higher Fn14 mRNA levels than patients without oropharyngeal dysphagia (P < 0.05). The results of immunofluorescence staining showed that 19 out of 23 PM/DM patients were TWEAK-positive, and 20 out of 23 PM/DM patients were Fn14-positive. No detectable expressions of TWEAK or Fn14 were observed in the healthy controls. CONCLUSIONS: TWEAK-Fn14 axis may be involved in the pathogenesis of PM/DM. Further understanding of TWEAK-Fn14 function in PM/DM may help to define therapeutic targets for PM/DM.

[Surfactant proteins-A and D as important serum markers for interstitial lung disease in patients with polymyositis or dermatomyositis].

OBJECTIVE: To explore the possible diagnostic values of serum surfactant protein-A (SP-A) and surfactant protein-D (SP-D) for interstitial lung diseases (ILD) in patients with polymyositis or dermatomyositis (PM/DM). METHODS: Serum MCP-1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in 100 adult PM/DM patients, 20 patients with pulmonary infection and 42 healthy controls. And the association with their clinical features and serum levels of SP-A and SP-D was analyzed. RESULTS: The serum levels of SP-A and SP-D in the PM/DM patients with ILD were both significantly higher than those without ILD and healthy controls (all P < 0.01) while there were no significance differences with those with infectious lung diseases (P > 0.05). The sensitivity of serum abnormal levels of SP-A, SP-D and combination of SP-A and SP-D for ILD in PM/DM patients were 66.1%, 64.3% and 80.0% and the specificity 72.7%, 72.7% and 70.2% respectively. The serum levels of SP-A were positively correlated with serum ferritin and C-reactive protein (CRP) and negatively with percent carbon monoxide diffusing capacity (DLCO%) (r = -0.474, P < 0.05), VC% (r = -0.404, P < 0.05) while the serum levels of SP-D were negatively correlated with circulating CD3+T cells (r = -0.244, P < 0.05) and CD4+T cells (r = -0.277, P < 0.05) in PM/DM patients. Furthermore, SP-A was an independent risk factor for death of ILD in PM/DM (OR 1.032, 95%CI 1.006 - 1.059, P < 0.05). CONCLUSION: SP-A and SP-D may be potential useful serum markers for the diagnosis of ILD in PM/DM patients. And the combined detection of SP-A and SP-D offers a higher sensitivity than either marker alone. As a risk factor, serum SP-A can predict the prognosis of PM/DM patients with ILD.

Clinical significance of peripheral blood lymphocyte subsets in patients with polymyositis and dermatomyositis.

Peripheral blood lymphocyte subsets were determined by flow cytometry in 89 Chinese patients with polymyositis (PM) and dermatomyositis (DM). We aimed to investigate the clinical significance of peripheral blood lymphocyte subsets in PM/DM. Patients with active DM showed significant decreases in numbers of CD3(+) cells, CD3(+)CD4(+) cells, and CD3(+)CD8(+) cells, as compared to patients with inactive DM and healthy controls (P < 0.05). CD3(+) and CD3(+)CD4(+) cell counts were significantly lower in DM before treatment, compared with after treatment (t = -5.714 and -3.665, P < 0.05). Counts of CD3(+) cells, CD3(+)CD4(+) cells, CD3(+)CD8(+) cells, and CD19(+)CD5(-) cells were all correlated with the total disease activity score as determined by the Myositis Disease Activity Assessment Visual Analogue Scale (P < 0.05). The decreased number of CD3(+) cells and the decreased percentage of CD3(+)CD4(+) cells were additionally correlated with the presence of interstitial lung disease in PM/DM (P < 0.05). The presence of levels of CD3(+)CD8(+) cells was risk factor for death (b = -0.011, OR = 0.989, P < 0.05). The identification of peripheral blood T lymphocyte subsets in PM/DM appears to be useful as a reference marker in the evaluation of clinical disease activity, and be useful in the comprehensive assessment of clinical lung involvement. A decrease in CD8(+) T cells may predict a poor outcome in patients with PM/DM.

[The levels and clinical significance of serum B cell activating factor in Chinese patients with polymyositis or dermatomyositis].

OBJECTIVES: To investigate serum levels of B cell activating factor (BAFF) in Chinese patients with polymyositis (PM) or dermatomyositis (DM), and analyze the correlation of BAFF with autoantibodies and clinical phenotypes. METHODS: Serum BAFF levels of 28 PM patients and 30 DM patients (study group), and 25 matched healthy controls (control group) were measured by ELISA. Serum anti-Jo-1 antibody levels were also measured by ELISA in all the subjects. The results of the two groups were compared by unpaired t test and the relevance was analyzed by Pearson's correlation analysis. RESULTS: Serum levels of BAFF in PM/DM patients were significantly higher compared to healthy controls (P = 0.000), but there was no statistically significant difference between the PM and DM patients (P > 0.05). Patients with interstitial lung disease (ILD) had significantly higher serum BAFF level than the patients without ILD (P = 0.000) or the controls (P = 0.000). Serum BAFF levels of patients with positive anti-nuclear antibody (ANA) were significantly higher than those with negative ANA (P = 0.003). For patients with anti-Jo-1 antibodies, the serum BAFF levels were correlated with the serum concentration of anti-Jo-1 antibodies (r = 0.799, P = 0.006). CONCLUSIONS: Serum levels of BAFF are increased in Chinese PM/DM patients. These findings indicate that BAFF may be possibly enrolled in the pathogenesis of PM/DM. Detecting serum BAFF levels could have some implication for the diagnosis and treatment of PM/DM.

[Measurement and clinical significance of serum monocyte chemoattractant protein-1 in patients with polymyosits/dermatomyosits].

OBJECTIVE: To analyze the correlated clinical significance by testing the serum monocyte chemoattractant protein-1 (MCP-1) levels of patients with polymyositis/dermatomyositis (PM/DM). METHODS: The sera from 100 adult PM/DM patients, 20 patients with pulmonary infection and 42 healthy controls were selected. The serum MCP-1 concentrations were detected by enzyme-linked immunosorbent assay (ELISA). The correlations between serum MCP-1 levels and clinical features or laboratory examinations of PM/DM patients were investigated. RESULTS: The serum levels of MCP-1 were (1 869 ±1 590) ng/L, (1 349±1 303) ng/L, (493±255) ng/L and (256±144) ng/L in PM/DM patients with interstitial lung disease (ILD) and without ILD, patients with infectious lung disease and healthy controls, respectively. Serum MCP-1 levels in the PM/DM patients with ILD were significantly higher than those of the PM/DM patients without ILD, patients with infectious lung disease and healthy controls (all P values<0.01). Significant correlations were found between the elevated levels of serum MCP-1 and the presence of ILD in the patients with PM/DM (χ2=9.6, P<0.01). The sensitivity and specificity of serum abnormal MCP-1 levels for ILD in the patients with PM/DM were 60.7% and 68.2%, respectively. The incidence of fever, arthritis, decreased %DL(CO) , erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum ferritin were significantly higher in the MCP-1 raised group than in the MCP-1 normal group (all P values<0.005). Additionally, Spearman rank correlation analysis showed that serum MCP-1 levels were positively correlated with serum ferritin in peripheral blood in the patients with PM/DM. CONCLUSION: The levels of serum MCP-1 are significantly elevated in PM/DM and it is significantly associated with ILD complication, and may contribute to the early differentiation of ILD from lung infectious disease.