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Objective:To analyze the frequency and characteristics of polymyositis (PM) in idiopathic inflammatory myopathy (IIM), and to investigate whether PM is over-diagnosed.Methods:Patients diagnosed as IIM according to the Bohan & Peter criteria of IIM hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2008 to 2019 were involved in the study. Definite PM (dPM) was defined as typical clinical and pathological features including elevated creatine kinase (CK) level, muscle weakness and muscle biopsy findings with endomysial CD8 + T cell infiltration and expression of MHC-1 on sarcolemma. Meanwhile, dermatomyositis (DM), anti-synthase syndrome(ASS), immune-mediated necrotic myopathy(IMNM), sporadic inclusion body myositis(sIBM) and other myopathies were excluded according to the new classification criteria of IIM subtypes respectively. Statistical analysis was performed using SPSS software 24.0. The Kruskal-Wallis test and χ2 test were used to compare the clinical characteristics between the dPM group and other IIM subtypes. Results:A total of 1 259 patients with IIM including 1 015 (80.6%) DM and 244(19.4%) PM were enrolled in this study. According to the strict definition of PM criteria, only 0.5% of patients (6/1 259) in IIM could be diagnosed as dPM. Most PM patients were IMNM and ASS according to the new IIM subtypes criteria, of which 48.0% (117/244) were IMNM and 32.0% (78/244) were ASS. 66.7%(4/6) of dPM patients were women. One complicated with RA, and one was dPM overlaped with systemic sclerosis. All of them had muscle weakness, mild elevation of CK level [611(391,1 451) U/L], and were myositis-specific autoantibodies negative. Except one dPM patients who did not receive immunoregulatory therapy due to chronic obstructive pulmonary disease, the others were administrated with low or medium dose prednisone combined with or without immunosuppressive agents. After a median follow-up of (38±26) months, the muscle strength of dPM patients were improved.Conclusion:dPM is a very rare clinical subtype of IIM. PM is an over-diagnosed entity in clinical practice. Patients with dPM have mild symptoms and good outcome.
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Objective:To identify dermatopathological features of patients with dermatomyositis (DM) and analyze its correlation with cutaneous diseases activity.Methods:The clinical data and skin biopsies of 48 patients were collected. The relevance was analyzed using Spearman's correlation analysis. The two groups were compared using Chi-square test or Fisher's exact test. Multi-factors line regression model was established to analyze the relationship between cutaneous disease activity and dermatopathological features.Results:The most common dermatopathological feature was perivascular inflammation (37 cases, 88%), followed by epidermal atrophy (22 cases, 52%) and melanocyte loss (20 cases, 48%), basal vacuolization (15 cases, 36%). The incidence of basal vacuolization ( χ2=9.110, P=0.022), interface dermatitis ( χ2=11.672, P=0.005) and mucin deposition ( χ2=7.795, P=0.029) were significantly different in patients with myositis specific antibody (MSA) subgroup. The patients with positive tranional intermediary factor-1 (anti-TIF1-γ) antibody had higher incidence of interface dermatitis and basal vacuolization, and patients with melanoma differentiation-associated gene 5 (anti-MDA5) antibody had lower incidence of interface dermatitis. Interface dermatitis was positively associated with epidermal atrophy ( r=0.371, P=0.016) and parakeratosis ( r=0.316, P=0.041). Pigment inco-ntinence was positively associated with basal vacuolization ( r=0.384, P=0.012). Multi-factor line regression showed interface dermatitis was positively related to cutaneous disease area and severity index (CDASI). Conclusion:The dermatopathological features is different in subgroup of patients with DM ( β=10.295, P=0.004). Interface dermatitis is a marker of cutaneous disease activity, and its pathogenesis may be different from that of perivascular inflammation. Keratinocytes may be involved in the pathological process in interface dermatitis.
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Objective:To investigate the pathological characteristics of skeletal muscle and its association with anti-aminoacyl-tRNA synthetases(ARS) antibodies and clinical features in patients with anti-synthetase syndrome (ASS).Methods:Patients diagnosed as ASS at China-Japan Friendship Hospital from 2008 to 2018 were involved in this study. Immunohistochemistry staining of MHC-Ⅰ, CD3, CD4, CD8 and CD20 molecule were performed in all muscle specimen taken from these patients. According to the muscular pathological characteristics, all patients could be divided into six pathological subgroups: pathologic DM(pDM), pathologic PM (pPM), unspecified myositis(USM), necrotizing myopathies (NAM), only MHC-Ⅰexpression (MHC-Ⅰ) and normal pathology groups. Immunoblotting assay was used to detect anti-ARS antibodies. Statistical analysis was performed using Statistical Product and Service Solutions (SPSS) software. T-test, Mann-Whitney U test and Analysis of Variance (ANOVA) were used for the comparison of measurement data. Chi-square test or Fisher's test were used for categorical data. P<0.05 was considered statistically significant. Results:A total of 77 patients underwent muscle biopsy and anti-ARS antibodies test, with the average age of (50±12) years and disease course of 9(3-24) months. The prevalence of anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ and anti-OJ antibodies in these patients was 47%(36 cases), 29%(22 cases), 12%(9 cases), 13%(10 cases) and 0 respectively. Among all the ASS patients, the most common pathological type was USM(37/77, 48%), followed by pDM(14/77, 18%), the normal pathology(13/77, 17%), NAM(10/77, 13%) and MHC-Ⅰ (3/77, 4%) groups. There were no pPM subtypes in all groups. The frequency of pDM types was significantly different among the anti-ARS antibodies groups( χ2=9.075, P=0.028). The anti-EJ-positive patients had a higher frequency of pDM compared with anti-PL-7-group(40% vs 4%, χ2=6.555, P=0.024). Meanwhile, the CD20 expression in muscle tissue was observed in 30% of anti-EJ-positive patients and 4% of anti-Jo-1-positive ones. There was statistically significant difference in the positive rate of CD20 expression among anti-ARS antibodies groups ( χ2=12.837, P<0.01). Conclusion:The muscle pathological characteristics of ASS are polymorphic and relate to the anti-ARS antibodies. Performing muscle biopsy and distinguishing pathological types are helpful for the diagnosis and stratification of ASS.
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Objective:To determine the serum levels of chemokine CCL27 and its clinical relevancein patients with dermatomyositis (DM).Methods:The serum CCL27 levels of 58 DM patients, 21 polymyositis (PM) patients, 20 systemic lupus erythematosus (SLE) patients and 31 healthy controls were measured by enzyme linked immunosorbent assay (ELISA). The score of disease activity was measured by two physicians-based on the myositis disease activity assessment tool (MDAAT). Its correlation with serum levels of CCL27 was analyzed. The difference between multiple groups were compared using analysis of variance (ANOVA) and t test, and the relevance was analyzed using Spearman correlation analysis and generalized method of moments (GEE) model. Results:Theserum level of CCL27 in DM patients (178±49) pg/ml was significantly higher than PM (110±40) pg/ml, SLE (141±46) pg/ml and healthy controls (137±38) pg/ml ( F=14.192, P<0.01). Crosssectional analysis showed that the serum CCL27 levelwaspositively correlated with global disease activity ( r=0.301, P=0.022) andskin disease activity ( r=0.493, P<0.01). Patients with V sign had higher serum CCL27 levels (191±52) pg/ml than the patients without (153±33) pg/ml ( t=2.839, P<0.01). Patients with holster sign had higher serum CCL27 levels (196±58) pg/ml than the patients without (168±41) pg/ml ( t=2.176, P=0.034). Follow-up study also found that CCL27l evels were positively correlated with global disease activity ( β=0.031, P=0.042) and skin disease activity ( β=0.032, P<0.01). Conclusion:The serum CCL27 levels are increased in patients with DM and can reflect the skin disease activity. The results of this study suggest that CCL27 may be a marker for cutaneous damage and monitoring of therapeutic effect.
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Objective To identify clinical features and risk factors in adult dermatomyositis (DM) with calcinosis.Methods Four hundred and eighty patients' clinical data were collected.The correlation between calcinosis and no calcinosis in adult DM were calculated by t test,x2 test and Mann-whitney U test.Multifactor logistic regression model was established to analyze independent factors for adult DM with calcinosis.Results Calcinosis occurred in 22 cases among these 480 patients with DM.The incidence of adult DM with calcinosis was 4.6％.Calcinosis was most common in the extremities and trunks.Patients with calcinosis had a longer disease duration [48 (24,120) months vs 10 (3,24) months,U=1993,P=0.000)] and more myothenia (95.5％ vs 76.9％,x2=4.192,P=0.038),panniculitis (9.1％ vs 0.4％,P=0.011),periungual erythematosus (22.7％ vs 5.89％,x2=7.044,P=0.008),skin ulcer (50.0％ vs 5.2％,x2=55.767,P=0.000),Raynaud's phenomenon (27.5％ vs 8.1％,x2=3.956,P=0.047).The anti-NXP2 antibody (27.3％ vs 3.9％,x2=19.416,P=0.000) and antiMDA5 antibody (31.8％ vs 12.9％,x2=4.851,P=0.028) were more frequently found in patients with calcinosis.Multi-factor logistic regression showed that anti-NXP2 antibody [OR=10.899,95％CI (2.593,45.816),P=0.001],long diseases duration [OR=1.105,95％CI(1.008,1.021),P=0.000] and skin ulcer [OR=31.585,95％CI(10.683),93.387,P=0.000] were risk factors for adult DM with calcinosis.Conclusion The incidence of calcinosisis in adult DM is 4.5％ in our cohort.Patients with calcinosis are adistinct clinical subset of adult DM.Long disease duration,skin ulcer and anti-NXP2 positive are independent risk factors for adult DM with calcinosis.
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Objective To investigate the association of distinct myositis specific autoantibodies (MSAs) with long-term survival of patients with polymyositis (PM) and dermatomyositis (DM).Methods We analyzed the clinical data and outcome of patients with PM and DM who were hospita-lized in the department of rheumatology of China-Japan Friendship hospital from 1994 to 2015,and evaluated the impact of MSAs on the prognosis of patients.Multivariate Cox regression analysis was used to identify the prognostic risk factors for PM/DM patients.Results A total of 383 PM/DM patients were followed up for 1-333 months.Cumulative survival and 10-year survival rate of all patients were 68.6％ and 76.2％,respectively.The survival rate of 80.4％ and 77.1％ at 3 and 5 years in patients with MSAs,which were lower than those of patients with-out MSAs,who had the survival rate of 90.1％ and 87.4％ at 3 and 5 years,respectively(x2=3.90 and 3.98,P＜0.05).There was significant difference for long-term survival in all MSAs positive groups (x2=40.654,P=0.000).Anti-MDA5 positive patients who had the 10-year survival rate of 28.7％ had the worst prognosis,while anti-HMGCR positive patients who had the l0-year survival rate of 100％ had the best outcome in all groups.Multivariate Cox regression analysis showed that independent risk factors associated with the long-term survival of patients were age of onset,complicated with malignancies,dysphagia,rapidly progress interstitial lung disease,antiMDA5 antibody positive,increased serum aspartate transferase and C reaction protein.Conclusion MSAs are strongly associated with the prognosis of patients with PM/DM.Patients with MSAs has worse 5-year overall survival than those without MSAs,which indicates that screening MSAs and aggressive treatment for PM/DM patients at very early stage of disease may improve the outcome.
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Objective To evaluate the clinical performance of chemiluminescent immunoassay (CLIA) on anti-nuclear antibody(ANA) specific autoantibodies testing.Methods A multi-center clinical study A total of 811 Sera samples were collected from 6 collaborating hospitals during the period of April to July 2016, and tested with CLIA and line immunoassay (LIA) in parallel for autoantibodies to ribonucleoprotein(RNP), smith antigen(Sm), SSA/Ro60,SSB/La, centromere protein B(CENPB), double-stranded DNA(dsDNA), nucleosome(Nuc), and ribosome P protein(Rib-P).The positive rate,specificity and qualitative coincidence rate for each antibody between CLIA and LIA methods were analyzed.All discrepant samples for systemic lupus erythematosus (SLE) highly specific autoantibodies (including anti-Sm, dsDNA, Nuc and Rib-P) were retested by enzyme linked immunosorbent assay (ELISA) and further analyzed with SLE disease cohort using McNemar test.Results The positive rate and specificity of CLIA and LIA for antibodies to ANA specific antigens were comparable.Excellent qualitative coincidence were found between CLIA and LIA for the detection of anti-RNP, SSA/Ro60, SSB/La and CENPB (Kappa>0.75), while the coincidence rate foranti-Sm, dsDNA, Nuc and Rib-P detection were moderate (0.4
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Objective The aim of this study is to analyze the prevalence of myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese dermatomyositis (DM) patients. Methods Four hundreds and twenty-seven DM patients were enrolled in this retrospective study. Clinical features and sera were collected. Twelve subtypes of MSAs were detected by commercial test kits. The correlations between MSAs and clinical phenotypes in DM patients were calculated by t test, Mann-Whitney U test or χ2 test. In order to clarify whether MSAs subsets would be independent factors of certain clinical feature or not, separate models were established to test the correlation via the Logistic regression analysis. Results The positivity of MSAs was 69.8% in 427 patients with DM. Anti-ARS, anti-MDA5 and anti-TIF1-γ antibodies were the three most common MSAs in the DM patients with positivity of 19.9%, 17.6%and 17.1% respectively. Different kinds of rash associated with MSAs subtypes by χ2 test. Certain MSAs subtype might be an independent factor for clinical features via logistic regression analysis. Interstitial lung disease (ILD) was observed more frequently in patients carrying anti-MDA5 [OR=5.266, 95%CI (2.522, 10.996), P<0.01] and anti-Jo-1 [OR=6.232, 95%CI (1.674, 23.199), P=0.006]. On the contrary, anti-Mi2 [OR=0.208, 95%CI (0.074, 0.580, P=0.003] and anti-TIF1-γ [OR=0.189, 95%CI (0.096, 0.370), P<0.01] were protective factors against developing ILD. Anti-TIF1-γ was an independent risk factor for cancer-associated myositis [OR=5.907, 95%CI (2.868, 12.168), P<0.01]. Anti-TIF1-γ[OR=2.789, 95%CI (1.594, 4.880) P<0.01], anti-NXP2 [OR=2.983, 95%CI (1.274, 6.982), P=0.012] and anti-SAE1 [OR=4.815, 95%CI (1.082, 21.424), P=0.039] could worsen dysphagic tendencies. In contrast, anti-MDA5 [OR=0.349, 95%CI (0.169, 0.720), P=0.004] might decrease the prevalence of this manifestation. Conclusion Patients with DM have a high frequency of MSAs. Some subtypes of MSAs are correlated with and may be independent factors of different clinical phenotypes. These indicated that MSAs can be useful biomarkers in monitoring the extramuscular features in DM patients.
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Objective The aim of this study is to analyze the prevalence of myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese dermatomyositis (DM) patients. Methods Four hundreds and twenty-seven DM patients were enrolled in this retrospective study. Clinical features and sera were collected. Twelve subtypes of MSAs were detected by commercial test kits. The correlations between MSAs and clinical phenotypes in DM patients were calculated by t test, Mann-Whitney U test or χ2 test. In order to clarify whether MSAs subsets would be independent factors of certain clinical feature or not, separate models were established to test the correlation via the Logistic regression analysis. Results The positivity of MSAs was 69.8% in 427 patients with DM. Anti-ARS, anti-MDA5 and anti-TIF1-γ antibodies were the three most common MSAs in the DM patients with positivity of 19.9%, 17.6%and 17.1% respectively. Different kinds of rash associated with MSAs subtypes by χ2 test. Certain MSAs subtype might be an independent factor for clinical features via logistic regression analysis. Interstitial lung disease (ILD) was observed more frequently in patients carrying anti-MDA5 [OR=5.266, 95%CI (2.522, 10.996), P<0.01] and anti-Jo-1 [OR=6.232, 95%CI (1.674, 23.199), P=0.006]. On the contrary, anti-Mi2 [OR=0.208, 95%CI (0.074, 0.580, P=0.003] and anti-TIF1-γ [OR=0.189, 95%CI (0.096, 0.370), P<0.01] were protective factors against developing ILD. Anti-TIF1-γ was an independent risk factor for cancer-associated myositis [OR=5.907, 95%CI (2.868, 12.168), P<0.01]. Anti-TIF1-γ[OR=2.789, 95%CI (1.594, 4.880) P<0.01], anti-NXP2 [OR=2.983, 95%CI (1.274, 6.982), P=0.012] and anti-SAE1 [OR=4.815, 95%CI (1.082, 21.424), P=0.039] could worsen dysphagic tendencies. In contrast, anti-MDA5 [OR=0.349, 95%CI (0.169, 0.720), P=0.004] might decrease the prevalence of this manifestation. Conclusion Patients with DM have a high frequency of MSAs. Some subtypes of MSAs are correlated with and may be independent factors of different clinical phenotypes. These indicated that MSAs can be useful biomarkers in monitoring the extramuscular features in DM patients.
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Objective To profile the differentially expressed genes in the muscle of polymyositis (PM) patients.Methods A mRNA microarray analysis was performed to profile mRNAs from 5 treatment-naive PM patients and 5 healthy controls.Gene Ontology and KEGG pathway analyses were applied to delineate the functional roles of the differentially expressed mRNAs.Quantitative real-time PCR analysis was conducted to validate the microarray data.The Student's t-test was used to analyze the statistical significance of the microarray results,and Benjamini-Hochberg FDR was used for multiple-test correction.Results Microarray analysis revealed that a total of 1 905 mRNAs (787 up-regulated and 1 118 down-regulated) were significantly differentially expressed in PM patients compared with the healthy controls (fold change＞2,P＜0.05).Six mRNAs were selected to analyze by quantitative RT-PCR to validate their expression levels and the results were consistent with that of the microarray analysis,and thus provide reliable validation for the microarray results.Gene ontology and KEGG pathway analysis for the differentially expressed mRNAs revealed that these genes were mainly involved in the biological process of infection and cytotoxic effect.In addition,there were some common signaling pathways that shared by PM and other autoimmune diseases.Conclusion There are differences in gene expressions between PM patients and healthy controls.The muscle damage in PM patients may be due to multi gene involvement and multi gene regulation.
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Objective This study aims to test the hypothesis that low density granulocytes (LDGs) is involved in the pathogenesis of DM associated-Interstitial lung disease (ILD).Methods Forty eight DM patients (28 with ILD) and 19 age-and sex-matched healthy Chinese volunteers were recruited to this study.LDGs percentage in peripheral blood mononuclear cells (PBMCs) was tested by flow cytometry.Neutrophilrelated genes (LL-37,MPO and MMP-8) expressions in PBMCs were tested by quantitative RT-PCR.Myositis disease activity assessment visual analogue scales (MYOACT) was used to assess the disease activity.Percentages of LDGs were compared in patients with ILD and without by using unpaired t test with Welch's correction,the correlations between LDGs and clinical parameters were further analyzed by linear correlation analysis.The expressions of neutrophil-related mRNA and proteins in PBMCs were compared by using MannWhitney U test.Results LDGs percentage in PBMCs was 7.1-fold higher in DM patients than healthy controls [(9.1±11.5)％ vs (1.3±0.7)％,t=4.664,P＜0.01].LDGs percentage in PBMCs was 2.7-fold higher in DM patients with ILD than DM patients without ILD [(12.3±14.1)％ vs (4.5±2.6)％,t=2.835,P=0.008 3].The mRNA expression level of LL-37,MPO and MMP-8 and LL-37 protein levels in the DM group were significantly higher than those in the control group.LDGs percentage positively correlated with MYOACT lung disease activity scores (r=0.439,P=0.010).Conclusion Percentage of LDGs in PBMCs is significantly increased in DM patients with ILD and positively correlated with MYOACT lung disease activity scores,suggesting that abnormall increasing of LDGs is a potential contributor to the pathogenesis of DM-associated ILD.
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Objective To determine the prevalence of microembolic signals (MES) by using transcranial Doppler (TCD) and to assess their association with neuropsychiatric systemic lupus erythematosus (NPSLE) and clinical presentations in patients with systemic lupus erythematosus (SLE).Methods Forty-four patients with SLE underwent TCD for 30 min were included for MES detection and their clinical information were recorded.In addition to the frequency of patients with MES,patients with MES were followed-up for sixmonth.Mann-Whitney U test and Fisher exact test were applied to investigate the clinical characteristics.Results There were 4 patients with history of NPSLE and the occurrence times were from 8 to 120 month before our study.There were 4 patients had the abnormal neuropsychiatric symptom during our study period.MES were detected in 5/44 patients (11％) with mean 17.6 per 30 min.MES were more prone to be detected in patients with higher systemic lupus erythematosus disease activity index (SLEDAI) score [16(12.5,19) vs 8(5,10),U=14.5,P=0.001],shorter course of disease [1(0.1,48.5) vs 26(13,55),U=38,P=0.028] and neuropsychiatric symptoms [3 vs 1,P=0.003].Conclusion MES may be detected in SLE patients.MES is associated with higher disease activity,shorter course of disease and NPSLE.TCD microemboli detection may be a noninvasive method to evaluate NPSLE patients.
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Objective To establish a new murine model of experimental autoimmune myositis by immunizing with MYBPC2 protein. Methods The purified Myosin-binding protein C, fast type (MYBPC2) was emulsified with complete Freundˊs adjuvant, then C57BL/6 mice were immunized by multi-point subcutaneous injection (0, 7 days), and intraperitoneal injection of pertussis toxin 2 μg simultaneously. The pathological changes of mice with different immunizing dose at the preconceived time were ex-plored. Mean-while, mice were immunized with 600 μg each time, and the muscle endurance was tested on the 21th day. The expression of major histocompatibility complex (MHC) class-Ⅰ and the surface biomarkers of the inflammatory cells in muscle tissues were observed. Mann-Whitney U test was used for statistical analysis. Results ① With the increase of immunizing dosage, muscle damage and inflammation tended to be more serious. On the 21th and 28th day, muscle lesions were most significant. Muscle fiber degeneration and necrosis and inflammatory cell infiltration could be seen in the experimental group. ② Compared with the control group, muscle endurance of mice in the experimental group decreased significantly [(6.1 ±1.3) min versus (9.2±1.6) min, U=2.00, P=0.017]. The MHC class-Ⅰ on the muscle fiber surface of the experimental group was positive, scattered infiltration of CD4 +, CD8+ T ly-mphocytes and CD68 + macrophages between muscle fibers and around the vascular areas could be observed, and CD20+B lymphocytes mainly distributed in the area around the blood vessels, nevertheless rarely seen between muscle fibers. Conclusion Exper-imental autoimmune myositis models of mice have been successfully induced by immunizing with MYBPC2 in China for the first time, and similar clinical and pathological features of human polymyositis could be observed. This new model can be used for studying the pathogenesis of autoimmune myositis.
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Objective To study the relationship between anti-transcription intermediary factor 1 family proteins (TIF1) autoantibodies profiles and cancer-associated dermatomyositis (CAM) and to define the diagnostic value of different subtypes of anti-TIF1 aotuantibodies for CAM.Methods The sera from 156 patients with dermatomyositis (DM),55 with polymyositis (PM),70 with systemic lupus erythematosus (SLE),60 with rheumatoid arthritis (RA),46 with primary Sj(o)gren syndrome (pSS),14 with systemic sclerosis (SSc),49 with kinds of malignancies and 40 healthy subjects were examined by immunoprecipitation assays followed by western blotting.Statistical analysis were performed using ANOVA,t test Mann-Wittney U and x2 test or Fisher exact test,nonparametric method was used to evaluate the sensitivity and specificity through calculating the area under the receiver operating characteristic curve (ROC).Results In summary,32 of 156 sera from patients with DM (20.5％) were positive for at least one anti-TIF1 autoantibodies.There are four subtypes of anti-TIF1 autoantibodies profiles existed in patients with DM,including 4 patients with only positive anti-TIF1-α (12.5％),20 with only positive anti-TIF1-γ (62.5％),7 with both positive anti-TIF1-α and anti-TIF1-γ (21.9％) and 1 with both positive anti-TIF1-β and anti-TIF1-γ (3.1％).However,only positive anti-TIF1-α (7.3％) was observed in 4 patients with PM.No patients with other CTDs as well as malignancy and healthy subjects were positive for these autoantibodies.The sensitivity and specificity of presence of anti-TIF1-α antibodies for the diagnosis of CAM were 42.9％ and 96.5％,respectively and those of anti-TIF1-β antibodies were 0 and 99.3％,respectively and those of anti-TIF-1-γ antibodies were 64.3％ and 86.6％,respectively.Application of areas of ROC to identify the best performance of test of anti-TIF1 antibodies profiles were 0.70,0.50,0.76,0.74 and 0.71,respectively.Conclusion Joint detection of antiTIF1 autoantibodies profiles can improve the diagnostic capbility for CAM.
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Objective To explore the correlations between elevated cfDNA with lupus nephritis and indentify the influencing factors of cfDNA in systemic lupus erythematosus (SLE).Methods Fifty four patients with SLE [37 patients with lupus nephritis (LN) and 43 age-and sex-matched healthy controls] were included in the study.In 37 LN patients,26 patients were at active stage,and 11 patients were in remission.cfDNA concentration was measured with Picogreen Kit and low-density granulocytes (LDGs) was tested by flowcytometer.Correlation and regression analysis were performed to discover whether cfDNA is related to LN and identify the influencing factor of cffDNA.Results The cfDNA in SLE group was (237±40) ng/ml,which was significantly higher than that in healthy control group (188±41 ng/ml,P＜0.01).cfDNA in LN group was significantly higher than that in patients without LN (NLN) (247±47 ng/ml vs 214±31 ng/ml,P=0.028).cfDNA in patients with active LN was significantly higher than that in patient with inactive LN (RLN) (254±50 ng/ml vs 216±29 ng/ml,P=0.035).In SLE group,cfDNA was positively correlated with quantitative 24-hour urinary protein (r=0.350,P=0.013) and reversely correlated with albumin (r=-0.500,P＜0.01) and endogenous creatinine clearance rate (Ccr) (r=-0.354,P=0.044).Percentage of LDGs in peripheral blood mononuclear ceils (PBMCs) of the SLE group was (8.3± 12.9)％,significantly was higher than that in healthy controls [(1.2±0.7)％,P=0.004].The cfDNA was positively correlated with LDGs (r=0.636,P=0.002) and neutrophils (r=0.599,P＜0.01).Conclusion NETs excessively released by neutrophils as well as LDGs may be one of the main reasons for elevated cfDNA level in SLE.cfDNA level is associated with LN activity,suggesting that there is a intrinsic link between NETs-related biomarkers and active LN and that more specific biomarkers of NETs may become a clinical biomarker for active LN.
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Objective To investigate the correlation between serum levels of B cell activating factor (BAFF) and disease activity in the patients with dermatomyositis (DM).Methods Serum BAFF levels of 61 patients with DM and 25 matched healthy controls were measured by ELISA.The results of the two groups were compared using unpaired Mann-Whitney U test and the relevance was analyzed using Spearman correlation analysis.Results Serum levels of BAFF in DM patients were significantly higher compared to healthy controls [(274 7±264 6) pg/ml 与 (832±170) pg/ml,Z=-5.492,P＜0.01].A cross-sectional assessment revealed that serum BAFF levels were positively correlated with global disease activity (r=0.501,P＜0.001),muscle disease activity (r=0.303,P＜0.05),and cutaneous disease activity (r=0.467,P＜0.01).High serum BAFF levels were associated with increased incidence of interstitial lung disease (x2=17.238,P＜0.01).The longitudinal study showed modest correlations between serum BAFF levels and global disease activity (r=0.658,P＜0.01),muscle disease activity (r=0.307,P＜0.05),as well as cutaneous disease activity (r=0.565,P＜0.01).Conclusion Serum levels of BAFF correlate with disease activity in DM patients.The results of this study suggest that BAFF is a serological biomarker for DM disease activity.
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Objective To determine the sera levels of anti-nuclear matrix protein (NXP)-2 autoantibodies and their clinical associations in patients with idiopathic inflammatory myopathies (IIM).Methods Sera from 198 Chinese patients with IIM including 15 juvenile dermatomyositis (JDM),133 dermatomyositis (DM) and 50 polymyositis (PM),other connective tissue diseases (CTDs) including 70 systemic lupus erythematosus,60 rheumatoid arthritis,15 systemic sclerosis,46 primary Sj(o)gren syndrome,10 mixed connective tissue disease and 60 healthy controls were measured by enzyme linked immunosorbent assay.The anti-NXP-2 antibodies were detected.The positive sera were further examined by immunoprecipitation assays.Statistical analyses were performed using student's t test or Mann-Wittney U test and x2 test.Results The positive rate of sera anti-NXP-2 autoantibodies in patients with IIM was 5.1％ (10/198),20.0％ (3/15) in patients with JDM,3.7％ (5/133) in patients with dermatomyositis,and 4.0％(2/50) in patients with polym-yositis.There was statistical significant difference in anti-NXP-2-positive rates between JDM,DM and PM (P＜0.05).However,the autoantibody did not present in patients with other CTDs as well as healthy controls.The anti-NXP-2-positive patients had significantly younger age [(33±20) vs (45±17) years old (t=-2.09,P＜0.05)] and higher incidence of calcinosis [30.0％(3/10) vs 2.6％(15/188)] compared with the anti-NXP-2-negativepatients (x2=0.7,P＜0.01).There were no statistical difference between the two groups in gender,disease duration,arthritis,rash,dysphagia,myasthenia,conccurrence with interstitial lung disease and cancer.In follow-up assessment,among the three JDM patients with anti-NXP-2 autoantibodies,one of them who died 10 months later had increased serum level of anti-NXP-2 autoantibody,extensive subcutaneous calcinosis,severe myasthenia and rapid progress.Conclusion This is the first report of the serum levels of anti-NXP-2 antibodies in Chinese patients with IIM and other CTDs.We find that anti-NXP-2 antibodies only exist in patients with IIM and are associated with early and calcinosis.
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Objective To investigate the value of MR DWI in the detection of early acute sacroiliitis in patients with spondyloarthritis(SpA).Methods The data of sacroiliac joint MRI were retrospectively analyzed in fifty-nine patients with inflammatory low back pain and negative plain radiographs and/or CT.T1WI,T2WI,short tau inversion recovery (STIR) and DWI images were obtained in all cases.Contrast-enhanced T1WI with fat suppression (FST1WI) images were obtained in 28 patients and follow-up MRI examinations were performed during treatment in 7 cases.Acute inflammatory lesion was defined as hyperintense signal located in subchondral or periarticular regions on STIR images and or on enhanced FST1WI.Cases were divided into acute inflammation group and non-inflammation group.Comparison was performed among STIR,enhanced FST1WI and DWI in the detection of acute inflammation by using Chi-square test.Mean ADC value was obtained from normal and inflammatory areas in acute inflammation group and from subchondral bone marrow in non-inflammation group,and t test was used for comparison of ADC values.Results Acute inflammation existed in 38 cases (72 sacroiliac joints) and acute inflammatory lesions displayed as high signal on DWI in 35 cases (67 sacroiliac joints).STIR,enhanced FST1WI and DWI showed no significant difference in the detection of acute sacroilliitis (37/38,38/38,36/38,respectively;x2=0.16,P=0.923).ADC values measured from acute inflammatory areas were significantly higher than values measured from normal area in acute inflammation group [(1.087± 0.207)× 10-3 and (0.537±0.091) × 10-3mm2/s],and values measured from subchondral bone marrow in non-inflammation group [(0.487±0.112) × 10-3mm2/s],there were significant difference (t values were 14.971 and 12.289,P＜0.01).ADC values were similar between normal area in acute inflammation group and subchondral bone marrow in non inflammation group (t=1.874,P=0.066).ADC values were (1.018±0.266) × 10-3 and (0.706±0.164) ×10-3mm2/s before and after the treatment (t=5.312,P＜0.01).Conclusions DWI is a sensitive method to display acute inflammatory lesions in sacroiliac joints.ADC values can be effectively used to quantify inflammatory lesions in acute sacroilliitis as well as in the evaluation of efficacy of treatment.
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Objective To investigate the availability of N-terminal pro-brain natriuretic peptide (NT proBNP) in the detection of early ventricular diastolic dysfunction by polymyositis/dermatomyositis (PM/DM).Methods A total of 46 PM/DM patients without symptoms of heart involvement were prospectively studied by standard echocardiography and the longitudinal mitral annular velocities was measured by tissue Doppler echocardiography (TDI).Plasma NT-proBNP was measured in all patients.Multivariate Logistics regression analysis was applied to investigate the risk factors for early cardiac complications.The availability of NTproBNP was evaluated by receiver operating characteristic (ROC) analysis.Results There were 22 patients complicated with early diastolic dysfunction (E/Em ≥ 8) by TDI.The multi-factors Logistic regression analysis showed that the age of onset (OR=1.117,95％CI 1.005-1.243,P=0.040) and plasma NT-proBNP (OR=1.022,95％CI 1.001-1.042,P=0.036) were risk factors for early left ventricular diastolic dysfunction.The level of NT-proBNP was positively correlated with E/Em value(r=0.687,P=0.000).ROC showed NT-proBNP could reliably detectearly ventricular diastolic dysfunction [area under the curve 0.858 (95％ CI 0.735-0.981,P＜0.01)].If PM/DM patients with normal TDI(E/Em＜8) were used as controls,and 120 pg/ml was used as the cut-off concentration,the sensitivity and specificity of NT-proBNP for the early ventricular diastolic dysfunction was 81.8％ and 91.7％ respectively.Conclusion Age at onset and plasma NT-proBNP are risk factors for early left ventricular diastolic dysfunction.The level of NT-proBNP is positively correlated with E/Em value.The plasma NT-proBNP concentration higher than 120 pg/ml maybe a marker for early left ventricular diastolic dysfunction.
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Objective To express the recombinant mouse histidyl-tRNA synthetase (HARS) and maltose binding protein (MBP) gene in Escherichia coli and obtain the purified protein which possesses antigen specificity.Methods Total RNA was extracted from the myocytes of C57BL/6 mouse and reversely transcripted to cDNA.The gene of N-terminal origin of 591 base pairs was amplified,then cloned into pMALc-5e vector.The recombinant plasmid was transformed into Rosetta-gami B,then IPTG was used to induce the expression of HARS-MBP.Fusion protein was purified by affinity chromatograph.The molecular weight (MW) of HARS-MBP was roughly determined by SDS-PAGE.The antigen specificity was identified by Western blotting using anti-Jo-1 serum from patients,commercial anti-HARS and anti-MBP antibodies.Results The recombinant HARS-MBP protein gene was efficiently expressed in Escherichia coli,and the MW was consistent with predicted MW of 66 000.The fusion protein was specifically combined with its antibody.Conclusion The HARS-MBP fusion protein could be efficiently and steadily synthesized in Escherichia coli,which shows satisfactory antigen specificity and provides the key requirement for making a deep study of HARS in the pathogenesis of idiopathic inflammatory myopathy(IIM) and animal modeling of IIM.