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Objectives: To clarify the clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM)., Methods: We retrospectively examined the clinical features and status of anti-Ro52 Abs in patients with PM/DM admitted to the University of Tsukuba Hospital between January 2019 and February 2023. We compared the anti-Ro52 Ab-positive and anti-Ro52 Ab-negative groups., Results: A total of 40 patients were selected and analysed. Twenty-three cases were PM, and 17 cases were DM (including six clinically amyopathic DM). Twenty-two cases were positive for anti-Ro52 Ab, 14 for anti-ARS Ab, and 6 for anti-MDA5 Ab. Interstitial lung disease was detected in 29 cases, nine of which were rapidly progressive. Glucocorticoid-resistant cardiomyopathy was detected in six cases. Of the 22 anti-Ro52 Ab-positive cases, only 3 were single-positive and the remaining 19 cases simultaneously had other autoantibodies. Comparing the anti-Ro52 Ab-positive and anti-Ro52 Ab-negative groups, the frequencies of anti-ARS Ab positivity (63.6% vs. 0%), interstitial lung disease (95.5% vs. 44.4%), glucocorticoid-resistant cardiomyopathy (27.3% vs. 0%), concomitant use of immunosuppressants (95.5% vs. 55.6%), and levels of C-reactive protein were significantly higher in the anti-Ro52 Ab-positive group (P < .05)., Conclusions: Anti-Ro52 Abs were frequently positive in PM/DM, and may be useful as a severity marker., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: Despite the well-established association between chronic inflammatory conditions and pulmonary embolism(PE), previous investigations of the relationship between Dermatomyositis(DM) and Polymyositis(PM) with PE were scarce and have been subject to significant limitations, including small sample sizes and failure to account for potential confounders., Objectives: To investigate the correlation between DM/PM and PE, as well as assessing the impact of serologic status, myonecrosis, and inflammation markers on this relationship., Methods: In this large, nationwide population-based study, we used the Clalit Health Services medical database and extracted all DM/PM patients who were first diagnosed between 1 January 2002 to 31 December 2018 and compared them with age and gender matched controls in a ratio of 1:5. Serological and laboratory values were obtained for each patient. Rates of PE were compared between groups using multivariate models., Results: The study included 1557 DM patients with 7633 controls, and 528 PM patients with 2560 controls. Compared with matched controls, the rates of PE were significantly higher in the DM/PM group, PM patients(2.8 % vs 0.5 % in controls, OR = 5.73, p < 0.001), DM patients(1.2 % vs 0.3 % in controls, OR = 3.42, p < 0.001). APLA seropositivity was significantly more prevalent in DM/PM patients compared with their matched controls, PM patients(10.8 % vs 2.7 % in controls, p < 0.001), DM patients(7.9 % vs 1.6 % in controls, p < 0.001). APLA seropositivity had a synergistic effect for PE in the DM/PM(OR = 23.18, p < 0.001)., Conclusions: DM and PM are associated with higher rates of PE. Furthermore, patients with DM/PM demonstrate a significantly higher prevalence APLA which act as a potentiator of thrombosis in these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: Growth differentiation factor 15 (GDF15) plays an important role in multiple inflammatory disorders. We aimed to analyze serum GDF15 levels in adult patients with idiopathic inflammatory myopathies (IIMs)., Methods: Serum GDF15 levels were measured in 179 adult patients with IIMs and 76 healthy controls (HCs). The association between GDF15 levels and disease variables was analyzed using Spearman's rank correlation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory ability of GDF15 and the GDF15-to-lymphocyte ratio (GLR). Machine learning methods were applied to build predictive models., Results: GDF15 levels and GLR were significantly elevated in patients with adult IIMs than in HCs. Compared with patients in remission, both GDF15 and GLR were significantly higher in myositis patients in an active phase. GDF15 levels correlated positively with myositis disease activity indices and negatively correlated with lymphocyte and platelet counts. ROC curve analysis revealed that GDF15 levels and GLR outperformed muscle enzymes and distinguished well between patients with active disease and those in remission. Furthermore, even in the normal muscle enzyme group, GDF15 levels and GLR were also well-distinguished between patients with active disease and those in remission. Using machine learning, a logistic regression model of GDF15 combined with creatine kinase and lymphocyte count was constructed and had a reliable predictive value for disease activity., Conclusions: GDF15, particularly GLR, was significantly correlated with disease activity in adult patients with IIMs. They could serve as useful biochemical markers for evaluating disease activity, monitoring disease progression, and guiding treatment in adult patients with IIMs., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Abstract: The aim of this study was to evaluate the association between clinical phenotypes of dermatomyositis (DM) and polymyositis (PM) with myositis-specific antibodies (MSAs), and overlap diagnosis of systemic autoimmune diseases.This cross-sectional study was conducted on 67 patients with DM and 27 patients with PM recruited from a regional hospital in southern Taiwan. Clinical phenotypes of DM and PM were assessed and MSAs were measured using a commercial line blot assay. The association of clinical phenotypes of DM and PM with MSAs and overlap diagnosis of systemic autoimmune diseases was performed using univariate and multiple logistic regression analyses.Clinically, patients with DM and PM and overlap diagnosis of systemic sclerosis were associated with a higher risk of interstitial lung diseases (ILDs) (odds ratio [OR] = 6.73; P = .048), Raynaud phenomenon (OR = 7.30; P = .034), and malignancy (OR = 350.77; P = .013). The risk of malignancy was also associated with older age (OR 1.31; P = .012), and male patients were associated with a higher risk of fever. For MSAs, anti-aminoacyl-tRNA synthetase antibodies were associated with ILD, antinuclear antibody were associated with a lower risk of arthritis, anti-transcription intermediary factor 1-gamma antibodies were associated with milder symptoms of muscle weakness, anti-Ku antibodies were associated with overlap diagnosis of systemic lupus erythematosus, and anti-Ro52 antibodies were associated with the development of Raynaud phenomenon and Sjögren syndrome.MSAs and overlap diagnosis of systemic sclerosis were significantly associated with clinical phenotypes of DM and PM. Physicians should be vigilant for malignancy in older DM and PM patients with overlap diagnosis of systeic sclerosis. The possibility of developing ILD in patients with overlap diagnosis of systemic sclerosis or serum positivity of anti-aminoacyl-tRNA synthetase antibodies should be considered., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Interleukin-35 (IL-35) is a recently described heterodimeric cytokine that belongs to the IL-12 family and consists of p35 (IL-12a) and EBI3 (IL-27b) subunits. The expression of IL-35 in humans is inducible in response to inflammatory stimuli. Increased IL-35 levels were documented in several autoimmune inflammatory diseases, suggesting a possible immunomodulatory role in their pathogenesis., Objectives: The aim of this study was to explore a potential role of IL-35 in the pathogenesis of idiopathic inflammatory myopathies (IIM) by studying the expression of IL-35 subunits in muscle biopsy samples and by evaluating serum levels of IL-35 and their association with disease activity in IIM patients., Methods: The expression of IL-35 subunits was studied in serial sections of 9 muscle biopsy samples [4 polymyositis (PM), 5 dermatomyositis (DM)] and in 7 non-inflammatory control muscle biopsies. Serum levels of IL-35 were measured in 23 PM, 28 DM and 15 cancer associated myositis (CAM) patients as well as in 40 healthy controls. Disease activity was evaluated using the Myositis Disease Activity Assessment Tool (MDAAT) and by serum muscle enzymes., Results: Expression of both IL-35 subunits was evident in the inflammatory infiltrates in IIM muscle biopsies, while no IL-35 expression was observed in control muscle samples. IL-35 serum levels were increased in all IIM patients compared to healthy controls [median 119.5 (range 32.1-1074.5) vs 36.2 (range 1.5-86.5) pg/ml, P < 0.001]. There were no differences in IL-35 serum levels between myositis subgroups (DM, PM or CAM). Serum IL-35 levels correlated significantly with physician's assessment of global (r = 0.29, p = 0.021), muscle (r = 0.30, p = 0.017) and extramuscular (r = 0.30, p = 0.016) disease activity as well as creatine kinase (r = 0.26, p = 0.044) and lactate dehydrogenase (r = 0.40, p = 0.003) levels. There was a significant correlation with pulmonary activity in patients with interstitial lung disease (r = 0.39, p = 0.037). Serum IL-35 correlated negatively with duration of treatment (r = -34, p = 0.009)., Conclusions: IL-35 is overexpressed in inflammatory infiltrates in muscle tissue and serum in IIM patients and there is correlation with several disease activity parameters. These data suggest potential role of locally produced IL-35 in the pathogenesis of inflammatory myopathies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Growing evidence from studies elsewhere have illustrated that microRNAs (miRNAs) play important roles in polymyositis and dermatomyositis (PM/DM). However, little has been reported on their relationship with regenerating islet-derived protein 3-alpha (REG3A) as well as their associative roles in macrophage migration. Therefore, this study sought to establish the association between miR-146a and REG3A as well as investigate their functional roles in macrophage migration and PM/DM pathogenesis. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from PM/DM patients and healthy controls through density centrifugation. Macrophages were obtained from monocytes purified from PBMCs via differentiation before their transfection with miRNA or plasmids to investigate cell migration with transwell assay. An experimental autoimmune myositis murine model was used to investigate PM/DM. Real-time PCR and Western blot analysis were conducted to determine the expression levels of miR-146a, interferon gamma (IFN-γ), interleukin (IL)-17A, and REG3A. Results: The messenger RNA (mRNA) expression level of miR-146a markedly decreased, while the mRNA level of REG3A, IFN-γ, and IL-17A expression increased substantially in PBMCs from PM/DM patients compared with the healthy controls. The levels of IFN-γ and IL-17A in serum from PM/DM patients was much higher than the healthy controls. Immunohistochemistry analysis showed that REG3A expression increased in muscle tissues from patients. Consistent with clinical data, the mRNA expression level of miR-146a also decreased, whereas the mRNA and protein level of REG3A, IFN-γ, and IL-17A significantly increased in the muscle tissues of experimental autoimmune myositis mice. Moreover, miR-146a inhibited monocyte-derived macrophage migration, and REG3A promoted macrophage migration. In addition, IL-17A induced REG3A expression, while miR146a inhibited expression of REG3A in monocyte-derived macrophages from the PBMCs of the healthy donors. Notably, inhibition of macrophage migration by miR-146a was via the reduction in REG3A expression. Conclusions: Reduced miR-146a expression in PM/DM leads to increased REG3A expression that increases inflammatory macrophage migration, which may be a possible underlying mechanism of DM/PM pathogenesis., (Copyright © 2020 Jiang, Huang, Liu, Xu, Gong, Chen, Hu, Han and Gao.)

Aim: The study aimed to investigate the changes in peripherallymphocyte and CD4 + T subsets and to observe the regulatory effect of low-dose interleukin-2 (ld-IL2) on these cells in polymyositis or dermatomyositis (PM/DM)., Methods: Lymphocyte subsets (CD3 + T, CD4 + T, CD8 + T, B and natural killer (NK) cells), CD4 + T subsets (Th1, Th2, Th17 and regulatory T (Treg) cells) and multiple cytokines of 71 patients after admission and treatment were measured by flow cytometry, as well as these indicators in 30 healthy controls (HCs). In DM, 35 cases were administrated with ld-IL2 combined with conventional therapy, the remaining 26 patients received conventional therapy only., Results: The numbers of CD3 + T and CD4 + T cells in PM/DM were markedly decreased. Meanwhile, the absolute number and percentage of peripheral Treg cells in PM/DM, as well as Th1 cells in DM, were significantly lower than those in HCs (P < 0.05), but Th2 and Th17 cells had no significant difference. The ratio of Th17/Treg in PM (P = 0.031) and in DM (P = 0.003) were obviously higher than that in HCs. The deficiency of Treg cells was associated with the occurrence of interstitial lung disease (ILD) in myositis patients. Meanwhile, reduced production of IL-2 was also observed in PM/DM (P < 0.001). ld-IL2 combination therapy could significantly increase the numbers of CD4 + T subsets in DM, especially Treg cells (expanded 2.5 times)., Conclusions: The decline of peripheral Treg cells and serum IL-2 were found in PM/DM. ld-IL2 combination therapy could significantly increase the number of Treg cells., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Idiopathic inflammatory myopathies are a heterogeneous group of potentially treatable myopathies. They are classified, on the basis of clinical and histopathological features, into four subtypes: dermatomyositis, polymyositis, necrotizing autoimmune myositis and inclusion-body myositis. Myositis-associated antibodies and myositis-specific autoantibodies are frequently found in patients with idiopathic inflammatory myopathies, and are useful in the diagnosis and classification. Anti-histidyl transfer RNA synthetase antibody is the most widely prevalent and is highly specific for polymyositis. Signal recognition particle antibody is also a specific autoantibody for polymyositis, but it is infrequent and rarely found in patients having other myositis-specific autoantibodies. We present a man with polymyositis who had both antibodies in serum, which is considered an extremely rare clinical situation. Here we analyze the clinical course and findings, and examine the effect of the coexistence and possible interaction on prognosis., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Interleukin (IL)-35 is confirmed as an important modulator in immune response. The aim of the study was to explore the role of IL-35 in the development of polymyositis/dermatomyositis (PM/DM). Ninety-five patients with PM/DM and 30 healthy controls (HCs) were recruited. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Paque Plus density gradient centrifugation. Protein IL-35, IL-17, and tumor necrosis factor (TNF)-α levels were measured using enzyme-linked immunosorbent assay method. The IL-35 serum levels in PM/DM patients were significantly higher than those in HCs and were correlated with PM/DM-related features: disease activity, muscle damage, and interstitial lung disease (ILD). Exogenous IL-35 notably suppressed lipopolysaccharide-induced IL-17 and TNF-α production in PBMCs of patients with PM/DM. Elevated serum IL-35 levels could act as a disease activity biomarker and an indicator of ILD in PM/DM. IL-35 may play an anti-inflammatory role in PM/DM.

Gout disease is an inflammatory arthritis that arises due to the accumulation of monosodium urate crystals (MSU) around the joints and in tissues. Clinical manifestation of metabolic diseases leading to secondary hyperuricemia most predominantly occurs in the form of gouty arthritis. Hyperuricemia and gout may develop during the course of glycogen storage diseases (GSD), particularly in GSD type I, which involves the liver. On the other hand, during the course of GSD type V (GSDV, McArdle's disease), which merely affects the muscle tissue due to the deficiency of the enzyme myophosphorylase, hyperuricemia and/or gout is rarely an expected symptom. These patients may mistakenly be diagnosed as having idiopathic hyperuricemia and associated gout, leading to the underlying secondary causes be overlooked and thus, diagnostic delays may occur. In this case report, we present a premenopausal female patient who experienced flare-ups of chronic arthritis while on disease-modifying antirheumatic drugs and intraarticular steroids due to a diagnosis of undifferentiated arthritis. The patient was initially suspected of having gouty arthritis because elevated concentrations of uric acid were incidentally detected, but then, a diagnosis of asymptomatic GSDV was made owing to elevated concentrations of muscle enzymes during colchicine use. Our aims were to remind rheumatologists of the phenomenon of "myogenic hyperuricemia" and to discuss the potential causes of hyperuricemia that develop during GSD along with the available literature.

Objective: This cross-sectional study was designed to assess the clinical significance of the serum KL-6 in the diagnosis of interstitial lung disease (ILD) in patients with idiopathic inflammatory myopathy (IIM)., Methods: We measured serum KL-6 levels in 184 patients with IIM using a chemiluminescent enzyme immunoassay and compared KL-6 levels between patients with and without ILD, according to other clinical features., Results: IIM patients with ILD had significantly higher serum KL-6 levels than those without ILD (776.5 [372.3-1378.8] vs. 297.5 [204.75-599.3] U/ml, P < 0.001). At a cut-off of 461.5 U/ml identified by ROC curve, serum KL-6 yielded a sensitivity of 70.2% and specificity of 73.9% for ILD in IIM patients. IIM patients with an elevated serum KL-6 were more likely to have clinical symptoms of mechanic's hands (P = 0.002), anti-Jo-1 antibody positivity (P = 0.021), dysphagia (P = 0.039), hoarseness (P < 0.001), and polyarthritis/polyarthralgia (P < 0.001). Significant inverse correlations were found between serum KL-6 levels and pulmonary function tests (P < 0.01), including forced vital capacity (FVC, %Pred), total lung capacity (TLC, %Pred), and diffusing capacity for carbon monoxide (DLCO, %Pred)., Conclusions: Serum KL-6 offers high sensitivity and specificity for the diagnosis of IIM-associated ILD and is inversely correlated with pulmonary function deterioration. Serum KL-6 may represent a promising biomarker for monitoring ILD severity in IIM patients.

Objectives: To assess serum interleukin (IL)-17A levels in patients with dermatomyositis (DM) and polymyositis (PM) and correlate them with the demographic, clinical, laboratory and therapeutic data of these diseases., Methods: This was a cross-sectional, single-centre study that included defined DM and PM patients who were age-, gender- and ethnicity-matched to healthy individuals. Serum IL-17A analysis, as well as analysis for other cytokines (IL-6, TNFα and IFNγ), was performed by multiplex immunoassay. The disease status parameters were based on the International Myositis Assessment and Clinical Studies Group (IMACS) set scores., Results: Eighty DM, 32 PM patients and 104 healthy individuals were enrolled. Mean age of patients with DM and PM was 46.0 and 47.7, respectively, with a predominance of women and white ethnicity in both groups. Overall, clinical, laboratory, therapeutic, and current disease status were similar among patients with DM and PM. Median serum IL-17A level was higher in patients with PM and DM than the control group (0.73 vs. 0.49 vs. 0.35 pg/mL, respectively; p<0.050) and higher in PM when compared to DM (p<0.001). In DM, serum IL-17A levels were associated with cumulative cutaneous lesions, IMACS parameters, and serum IL-6 and IFNγ levels. In PM, serum IL-17A levels correlated with patients' current age, IMACS parameters and serum TNFα and IFNγ levels., Conclusions: Serum IL-17A levels are not only increased, but also associated with disease activity in patients with DM and PM. Our data strongly suggest that IL-17A may be a biomarker of disease activity for these systemic autoimmune myopathies.

Myositis-specific autoantibodies, such as anti-melanoma differentiation associated gene 5 (MDA5) and anti-anti-amino acyl-tRNA synthetases (ARS) antibodies, are associated with interstitial lung diseases (ILD), which determine the prognosis of polymyositis/dermatomyositis (PM/DM) patients. However, there is a paucity of data on the clinical correlation between anti-Sjögren syndrome-related antigen A (anti-SSA)/Ro52 antibodies in PM/DM. We investigated the prevalence of myositis-specific autoantibodies including anti-SSA/Ro52 antibody and assessed the clinical significance of these antibodies in patients with PM/DM.We retrospectively reviewed demographic data and clinical outcomes in patients with PM/DM. The study population comprised 24 patients with PM and 60 patients with DM. The presence of anti-myositis-specific antibodies (MDA5, ARS, Jo-1, SSA/Ro52) was determined by immunosorbent assay (ELISA).Anti-MDA5 antibody was detected in 18 patients with DM (n = 60). Anti-ARS/anti-SSA/Ro52 antibodies were detected in 31 and 39 patients with PM/DM (n = 84). Rapidly progressive ILD patients were mainly found in the anti-MDA5 antibody-positive DM group. During the follow-up period, 9 patients died. Kaplan-Meier analysis demonstrated that survival rates seem to be lower in DM patients with anti-MDA5 antibodies compared with those without anti-MDA5 antibodies. Furthermore, dual positivity for anti-SSA/Ro52 and anti-MDA5 antibodies was significantly higher in nonsurviving DM patients compared with survivors.Although the presence of anti-ARS or anti-MDA5 antibodies is a prognostic marker in patients with PM/DM, combined presence of anti-SSA/Ro52 and anti-MDA5 antibodies represent another marker for clinical outcome in DM patients. Our results suggest that anti-SSA/Ro52 antibody positivity in DM patients with anti-MDA5 antibody reveals a subgroup of DM patients with poor prognosis.

Objectives: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and pathogenesis of autoimmune diseases, including polymyositis (PM) and dermatomyositis (DM). In this study, we examined the level and origin of serum-soluble TRAIL (sTRAIL) in patients with PM and DM and analyzed its association with disease activity and clinical features., Method: 11 PM patients, 33 DM patients, and 20 healthy controls were enrolled in this study. Clinical features were recorded when admitted, and disease activity was evaluated by myositis disease activity assessment visual analogue scale (MYOACT). TRAIL expression in muscle tissues was detected by immunohistochemistry. Serum sTRAIL levels were measured by enzyme-linked immunosorbent assay. The expression of membrane TRAIL (mTRAIL) and its receptors, including DR4 and DR5, on circulating T cells was analyzed by flow cytometry., Results: TRAIL was expressed in infiltrated inflammatory cells in muscle tissues from patients. The serum sTRAIL level was markedly increased in patients and was positively correlated with the disease activity. Serum sTRAIL was decreased after therapy in patients and was specifically higher in patients with dysphagia, but lower in patients with autoantibody Jo-1 positive. The frequency of mTRAIL and its receptors on circulating T cells from patients were significantly elevated than that from healthy controls., Conclusions: The serum sTRAIL could be a biomarker for evaluating the disease activity of PM and DM, and targeting the generation of TRAIL in T cells might be a potential approach in the treatment of PM and DM.

Introduction: Short tau inversion recovery (STIR) sequences in whole-body MRI are usually used for detecting muscle edema (ME) in inflammatory myopathies. We evaluated b-value 800 diffusion-weighted imaging (b800 DWI)., Methods: Two radiologists independently and a consensus reader retrospectively reexamined 60 patients with inflammatory myopathies and 15 controls. For each participant, 78 muscles were analyzed with 3 sets of imaging acquisitions: T1-weighted (T1) turbo spin echo and STIR; T1 and DWI; and T1, STIR and DWI. Mean edema per patient was compared between sequences. Agreement was evaluated., Results: Diffusion-weighted imaging detected more ME compared with STIR (P < 0.001). Agreement between readers was better with both sequences (k = 0.94) than with b800 DWI (k = 0.89) or STIR (k = 0.84) alone., Discussion: Diffusion-weighted imaging is a valuable add-on for the study of inflammatory myopathies. Muscle Nerve 59:555-555, 2019., (© 2019 Wiley Periodicals, Inc.)

Objectives: To identify factors associated with deterioration of pulmonary function with disproportional decline in diffusing capacity for carbon monoxide (DLCO) relative to forced vital capacity (FVC) in patients with dermatomyositis (DM) and polymyositis (PM)., Methods: This retrospective cohort study included patients with DM and PM, in whom serial pulmonary function tests were available. Changes in FVC and DLCO over time were estimated using a linear mixed-effects model., Results: A total of 103 patients were included. During follow-up, 31 (30.1%) and 37 (35.9%) had a disproportionally better (ΔDLCO/ΔFVC>mean slope + 95% CI) or a disproportionally worse (ΔDLCO/ΔFVC

C1q is an important component of the classical complement pathway. This study aimed to investigate C1q concentrations in the sera of PM/DM patients. C1q concentrations were measured in the sera of 87 PM/DM patients and 100 healthy subjects. In addition, the association between C1q concentration and laboratory indexes such as CK, AST, ALT, LDH, hsCRP, and ESR were also evaluated. Our data indicated no significant difference in the serum C1q concentration between PM/DM patients and healthy subjects. However, serum C1q concentrations were observed to be significantly higher in PM/DM patients in patients group with elevated ESR than in those with normal ESR (207.55±37.54 mg/L and 180.69±38.90 mg/L, respectively; P =0.008). Furthermore, there was a positive correlation between serum C1q concentration and ESR ( P =0.002), but no association was observed with CK, AST, ALT, LDH, and hsCRP levels. This study demonstrated C1q levels were elevated in PM/DM patients with higher ESR and revealed significant positive correlation. However, the exact role of the classical complement pathway in PM/DM needs further elucidation., (© 2019 by the Association of Clinical Scientists, Inc.)

Objective: This study aims to detect serum levels of monocyte chemoattractant protein-1 (MPC-1) and transforming growth factor-β1 (TGF-β1) in polymyositis/dermatomyositis (PM/DM) patients complicated with interstitial lung disease (ILD), to reveal the significance of the changes in these levels in the pathogenesis of PM/DM complicated with ILD., Methods: Serum MCP-1 and TGF-β1 levels in PM/DM patients complicated with ILD, patients with pulmonary infections and normal controls (n = 30, each) were detected using enzyme-linked immunosorbent assay (ELISA), and the correlation between PM/DM complicated with ILD and serum MCP-1 and TGF-β1 levels was analyzed., Results: Serum MCP-1 and TGF-β1 levels were both higher in PM/DM patients complicated with ILD compared with patients with pulmonary infections and normal controls., Conclusion: Serum MCP-1 and TGF-β1 levels increased in PM/DM patients, and were closely correlated to the complication of ILD. This finding can be used for distinguishing between pulmonary infections and ILD, providing a new diagnostic method for the early prediction of DM/PM complicated with ILD.

Background: Serum YKL-40 has been proved to be a promising biomarker for estimating the disease activity of several autoimmune diseases. However, its utility in polymyositis or dermatomyositis has not been established. The aim of this study was to investigate the utility of YKL-40 in patients with polymyositis/dermatomyositis., Method: Patients with definite polymyositis/dermatomyositis who visited the Second People's Hospital of Wuxi between April 2016 and March 2017 were prospectively enrolled. Eighty-seven healthy individuals were set as a control. Serum YKL-40 of all participants was determined using ELISA. The associations between YKL-40 and clinical characteristics of polymyositis/dermatomyositis were analysed using the Student's t-test, Mann-Whitney test and receiver operating characteristic curve analysis., Results: A total of 99 patients with polymyositis/dermatomyositis were enrolled. The patients with polymyositis/dermatomyositis had significantly higher serum YKL-40 concentration. Patients with interstitial lung disease had significantly higher YKL-40 concentration than those without. Serum YKL-40 was positively correlated with myositis disease activity assessment visual analogue scale, C-reactive protein, erythrocyte sedimentation rate and ferritin. The area under receiver operating characteristic curve of YKL-40 for identifying interstitial lung disease was 0.82., Conclusions: Serum YKL-40 is a useful biomarker for estimating disease activity or severity of polymyositis/dermatomyositis.

Myocardial injury with systemic sclerosis (SSc) causes pericarditis and arrhythmia, and polymyositis-induced muscle inflammation causes myocarditis. We report a rare case of overlap syndrome (SSc and polymyositis) who presented with sudden chest pain secondary to myocardial fibrosis. Although the etiology of chest symptoms in collagen disease was difficult to identify, cardiac magnetic resonance imaging (MRI) revealed not myocarditis but myocardial fibrosis in our case. Synthetic judgement of serum brain natriuretic peptide/ troponin T levels and cardiac MRI is useful in the search for the cause of chest symptoms even in patients with collagen diseases.

We aimed to evaluate in vivo effects of abatacept on phenotypes of T and B cells in the circulation of myositis patients in a sub-study of the ARTEMIS trial. Twelve patients with paired frozen PBMCs before and after 6-month abatacept treatment were included in this sub-study where mass cytometry (CyTOF) was chosen as a technology to be tested for its utility in a real-life clinical immune monitoring setting. Using CyTOF, the peripheral T cell phenotypes demonstrated considerable variation over time and between individuals precluding the identification of treatment-specific changes. We therefore conclude that studies of patient cohorts displaying wide clinical heterogeneity using mass cytometry must be relatively large in order to be suited for discovery research and immune monitoring. Still, we did find some correlations with functional muscle outcome, namely positive correlations between the ratio of CD4 + T cells and CD8 + T cells (CD4/CD8) in peripheral blood samples both at baseline and after treatment with muscle endurance improvement as assessed by the functional index-2 (FI-2) test. Our data suggest that the CD4/CD8 ratio in circulation at time of active disease may be a predictor of treatment efficacy in myositis patients., (© 2018 The Foundation for the Scandinavian Journal of Immunology.)

Objective: Cigarette smoking is associated with immune-mediated disorders. We explored the contribution of smoking to polymyositis (PM) and dermatomyositis (DM) phenotypes and attempted to determine whether cigarette smoking effects differ by race and genotype., Methods: Associations of tobacco smoking with disease features, autoantibodies, HLA types, and race were evaluated using multiple logistic regressions in 465 patients., Results: Caucasian ever-smokers (n = 140) were more likely to have PM (adjusted OR = 2.24, 95% CI: 1.41\x963.57), anti-synthetase (adjusted OR = 1.93, 95% CI: 1.12\x963.34) and anti-Jo-1 autoantibodies (adjusted OR = 1.94, 95% CI: 1.08\x963.46) and less likely to have anti-p155/140 autoantibodies (adjusted OR = 0.36, 95% CI: 0.14\x960.92). In Caucasians, ever-smokers had a greater interstitial lung disease (ILD) frequency than never-smokers, while in African-Americans this relationship was inverted, but neither trend reached statistical significance. Pack-years of cigarette smoking showed significant positive associations with PM (adjusted OR = 1.02, 95% CI: 1.002\x961.04) and ILD (adjusted OR = 1.02, 95% CI: 1.001\x961.03) and was inversely associated with anti-p155/140 autoantibodies (adjusted OR = 0.93, 95% CI: 0.87\x960.99) in Caucasians. Caucasian heavy smokers (=20 pack-years) were more likely to have PM (adjusted OR = 2.52, 95% CI: 1.25\x965.09), ILD (adjusted OR = 2.48, 95% CI: 1.23\x965.00) and anti-Jo-1 autoantibodies (adjusted OR = 2.65, 95% CI: 1.16\x966.08) than never-smokers. In Caucasians, compared to never-smokers without HLA-DRB1*03:01 allele, ever-smokers with HLA-DRB1*03:01 allele had the highest odds of PM, ILD, ASA, and anti-Jo-1 autoantibodies. Risks for those with only one of these two factors were intermediate. An inverse pattern was observed regarding anti-p155/140 autoantibodies., Conclusion: Tobacco smoking was associated with clinical and autoantibody phenotypes in Caucasians. Our findings also suggest possible interactions among HLA-DRB1*03:01 and smoking on the risk of PM and ILD, as well as, anti-synthetase, anti-Jo-1, and anti-p155/140 autoantibodies in Caucasians., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The downregulation of microRNA (miR)-381 has been detected in various diseases. The present study aimed to investigate the effects, and underlying mechanisms of miR-381 on inflammation and macrophage infiltration in polymyositis (PM). A mouse model of experimental autoimmune myositis (EAM) was generated in this study. Hematoxylin and eosin staining was conducted to detect the inflammation of muscle tissues. In addition, ELISA and immunohistochemistry were performed to determine the expression levels of associated factors, and reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression levels of related mRNAs and proteins. A luciferase activity assay was used to confirm the binding of miR-381 and high mobility group box 1 (HMGB1) 3' untranslated region. Transwell assays were also performed to assess the migratory ability of macrophages. The results demonstrated that serum creatine kinase (s-CK), HMGB1 and cluster of differentiation (CD)163 expression in patients with PM were increased compared within healthy controls. Conversely, the expression levels of miR-381 were downregulated in patients with PM. Furthermore, high HMGB1 expression was associated with poor survival rate in patients with PM. In the mouse studies, muscle inflammation and CD163 expression were decreased in the anti-IL-17 and anti-HMGB1 groups, compared with in the EAM model group. The expression levels of s-CK, HMGB1, IL-17 and intercellular adhesion molecule (ICAM)-1 were also downregulated in response to anti-IL-17 and anti-HMGB1. These findings indicated that HMGB1 was closely associated with inflammatory responses. In addition, the present study indicated that transfection of macrophages with miR-381 mimics reduced the migration of inflammatory macrophages, and the expression levels of HMGB1, IL-17 and ICAM-1. Conversely, miR-381 inhibition exerted the opposite effects. The effects of miR-381 inhibitors were reversed by HMGB1 small interfering RNA. In conclusion, miR-381 may reduce inflammation and the infiltration of macrophages; these effects were closely associated with the downregulation of HMGB1.

Background: Polymyositis (PM) and dermatomyositis (DM) are two distinct subgroups of idiopathic inflammatory myopathies, a chronic inflammatory disorder clinically characterized by muscle weakness and inflammatory cell infiltrates in muscle tissue. In PM, a major component of inflammatory cell infiltrates is CD8+ T cells, whereas in DM, CD4+ T cells, plasmacytoid dendritic cells, and B cells predominate. In this study, with the aim to differentiate involvement of CD4+ and CD8+ T-cell subpopulations in myositis subgroups, we investigated transcriptomic profiles of T cells from peripheral blood of patients with myositis., Methods: Total RNA was extracted from CD4+ T cells (PM = 8 and DM = 7) and CD8+ T cells (PM = 4 and DM = 5) that were isolated from peripheral blood mononuclear cells via positive selection using microbeads. Sequencing libraries were generated using the Illumina TruSeq Stranded Total RNA Kit and sequenced on an Illumina HiSeq 2500 platform, yielding about 50 million paired-end reads per sample. Differential gene expression analyses were conducted using DESeq2., Results: In CD4+ T cells, only two genes, ANKRD55 and S100B, were expressed significantly higher in patients with PM than in patients with DM (false discovery rate [FDR] < 0.05, model adjusted for age, sex, HLA-DRB1*03 status, and RNA integrity number [RIN]). On the contrary, in CD8+ T cells, 176 genes were differentially expressed in patients with PM compared with patients with DM. Of these, 44 genes were expressed significantly higher in CD8+ T cells from patients with PM, and 132 genes were expressed significantly higher in CD8+ T cells from patients with DM (FDR < 0.05, model adjusted for age, sex, and RIN). Gene Ontology analysis showed that genes differentially expressed in CD8+ T cells are involved in lymphocyte migration and regulation of T-cell differentiation., Conclusions: Our data strongly suggest that CD8+ T cells represent a major divergence between PM and DM patients compared with CD4+ T cells. These alterations in the gene expression in T cells from PM and DM patients might advocate for distinct immune mechanisms in these subphenotypes of myositis.

Thymomas are associated with autoantibody formation. The most common are anti-acetylcholine receptor antibodies, which correspond to myasthenia gravis (MG). Other autoantibodies, such as antistriational antibodies, can occur, but their relation to clinical syndromes is frequently uncertain. The etiology of antistriational antibodies is also poorly understood. In this case, a 61-year-old man with a history of thymoma was admitted with respiratory failure. The patient was positive for anti-acetylcholine receptor antibodies and antistriational antibodies. He developed cardiogenic shock and died within 2 days despite aggressive therapy. Laboratory studies revealed elevated cardiac enzymes and marked IgG elevation against Coxsackie A virus serotypes 9 and 24. Subclinical IgG elevations against additional Coxsackie A and Coxsackie B virus serotypes were also noted. Autopsy revealed lymphohistiocytic infiltrates with multinucleated giant cells in the myocardium and skeletal muscles, including the diaphragm. Giant cell polymyositis and myocarditis is a rare, lethal complication in patients with thymoma and MG. The pathogenesis is uncertain. An autoimmune process, possibly elicited by antistriational antibodies, has been suggested. The coexistence of antistriational antibodies and Coxsackie viral serologies has not been reported. This case may suggest that giant cell polymyositis and myocarditis in patients with thymoma and MG is a postviral autoimmune process.

The objective of this study was to investigate the clinical significance of the Wnt/β-catenin signaling pathway in glucocorticoid-induced osteoporosis. A total of 91 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg daily) were prospectively enrolled. We measured serum levels of N-terminal peptide of type I procollagen (P1NP), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), N-telopeptide cross-linked type I collagen (NTX), sclerostin, Dickkopf-1 (Dkk-1), and Wnt3a before starting glucocorticoid therapy and every week for 4 weeks after its initiation. The effects of dexamethasone on expression of mRNA and protein of sclerostin and Dkk-1 by cultured normal human osteoblasts (NHOst) were evaluated by RT-PCR and ELISA, respectively. Serum levels of sclerostin and Dkk-1 increased significantly by 1 week of glucocorticoid therapy and then decreased from the second week onward. Serum Wnt3a tended to decrease and serum P1NP showed a significant decrease. However, TRACP-5b was significantly elevated from the first week of treatment onwards. In vitro study, dexamethasone increased Dkk-1 mRNA expression in cultured NHOst, but sclerostin mRNA was not detected. Dexamethasone also increased Dkk-1 protein production by osteoblasts, whereas sclerostin protein was not detected. Bone formation might be impaired at least in the first week of the initiation of glucocorticoid therapy by increase of the serum Wnt signaling inhibitors; however, their reductions in the subsequent weeks were contradictory to the maintained suppression of the bone formation markers after glucocorticoid therapy for patients with systemic autoimmune diseases.

Background: The prevalence of dermatomyositis (DM) versus DM and polymyositis (PM) combined has been shown to be negatively associated with latitude. This observation has been attributed to increasing exposure to ultraviolet (UV) light towards the equator. In this study, we investigated whether differing genetic background in populations could contribute to this distribution of DM., Methods: Case data derived from the MYOGEN (Myositis Genetics Consortium) Immunochip study (n = 1769) were used to model the association of DM prevalence and DM-specific autoantibodies with latitude. Control data (n = 9911) were used to model the relationship of human leucocyte antigen (HLA) associated with DM autoantibodies and DM or PM single-nucleotide polymorphisms (suggestive significance in the Immunochip project, P < 2.25 × 10 - 5 ) in healthy control subjects with latitude. All variables were analysed against latitude using ordered logistic regression, adjusted for sex., Results: The prevalence of DM, as a proportion of DM and PM combined, and the presence of anti-transcription intermediary factor 1 (anti-TIF1-γ) autoantibodies were both significantly negatively associated with latitude (OR 0.96, 95% CI 0.95-0.98, P < 0.001; and OR 0.95, 95% CI 0.92-0.99, P = 0.004, respectively). HLA alleles significantly associated with anti-Mi-2 and anti-TIF1-γ autoantibodies also were strongly negatively associated with latitude (OR 0.97, 95% CI 0.96-0.98, P < 0.001 and OR 0.98, 95% CI 0.97-0.99, P < 0.001, respectively). The frequency of five PM- or DM-associated SNPs showed a significant association with latitude (P < 0.05), and the direction of four of these associations was consistent with the latitude associations of the clinical phenotypes., Conclusions: These results lend some support to the hypothesis that genetic background, in addition to UV exposure, may contribute to the distribution of DM.

Background: Polymyositis (PM) and dermatomyositis (DM) are severe chronic autoimmune diseases, characterized by muscle fatigue and low muscle endurance. Conventional treatment includes high doses of glucocorticoids and immunosuppressive drugs; however, few patients recover full muscle function. One explanation of the persistent muscle weakness could be altered lipid metabolism in PM/DM muscle tissue as we previously reported. Using a targeted lipidomic approach we aimed to characterize serum lipid profiles in patients with PM/DM compared to healthy individuals (HI) in a cross-sectional study. Also, in the longitudinal study we compared serum lipid profiles in patients newly diagnosed with PM/DM before and after immunosuppressive treatment., Methods: Lipidomic profiles were analyzed in serum samples from 13 patients with PM/DM, 12 HI and 8 patients newly diagnosed with PM/DM before and after conventional immunosuppressive treatment using liquid chromatography tandem mass spectrometry (LC-MS/MS) and a gas-chromatography flame ionization detector (GC-FID). Functional Index (FI), as a test of muscle performance and serum levels of creatine kinase (s-CK) as a proxy for disease activity were analyzed., Results: The fatty acid (FA) composition of total serum lipids was altered in patients with PM/DM compared to HI; the levels of palmitic (16:0) acid were significantly higher while the levels of arachidonic (20:4, n-6) acid were significantly lower in patients with PM/DM. The profiles of serum phosphatidylcholine and triacylglycerol species were changed in patients with PM/DM compared to HI, suggesting disproportionate levels of saturated and polyunsaturated FAs that might have negative effects on muscle performance. After immunosuppressive treatment the total serum lipid levels of eicosadienoic (20:2, n-6) and eicosapentaenoic (20:5, n-3) acids were increased and serum phospholipid profiles were altered in patients with PM/DM. The correlation between FI or s-CK and levels of several lipid species indicate the important role of lipid changes in muscle performance and inflammation., Conclusions: Serum lipids profiles are significantly altered in patients with PM/DM compared to HI. Moreover, immunosuppressive treatment in patients newly diagnosed with PM/DM significantly affected serum lipid profiles. These findings provide new evidence of the dysregulated lipid metabolism in patients with PM/DM that could possibly contribute to low muscle performance.

Objectives: Autoantibodies recognising cytosolic 5'-nucleotidase 1A (NT5C1A) are found in adult patients with myositis and other autoimmune diseases. They are especially prevalent in adults with inclusion body myositis (IBM), in which they are associated with more severe weakness and higher mortality. This study was undertaken to define the prevalence and clinical features associated with anti-NT5C1A autoantibodies in juvenile myositis., Methods: We screened sera from 380 patients with juvenile myositis, 30 patients with juvenile idiopathic arthritis (JIA) and 92 healthy control children for anti-NT5C1A autoantibodies. Clinical characteristics were compared between patients with myositis with and without anti-NT5C1A autoantibodies., Results: Anti-NT5C1A autoantibodies were present in 102 of 380 (27%) patients with juvenile myositis and in 11 of 92 (12%) healthy control children (P=0.002) and 27% of children with JIA (P=0.05 vs controls). Sera of 83 of 307 (27%) patients with juvenile dermatomyositis and 16 of 46 (35%) patients with juvenile overlap myositis were anti-NT5C1A autoantibody-positive (P<0.01 vs healthy controls for each), but sera of only 3 of 27 (11%) patients with juvenile polymyositis were anti-NT5C1A-positive. Patients with juvenile myositis with and without anti-NT5C1A autoantibodies had similar clinical phenotypes. However, patients with anti-NT5C1A autoantibody-positive myositis had greater pulmonary symptoms at diagnosis (P=0.005), more frequent hospitalisations (P=0.01) and required a larger number of medications (P<0.001)., Conclusion: Anti-NT5C1A autoantibodies are present in more than one-quarter of children with juvenile myositis and JIA compared with only 12% of healthy children, suggesting they are myositis-associated in children. As in adults with IBM, patients with juvenile myositis with anti-NT5C1A autoantibodies have more severe disease., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: To compare the prevalence of the anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) in Hong Kong Chinese patients with dermatomyositis (DM) and polymyositis (PM); in addition, to examine the association of anti-MDA5 Ab and the clinical characteristics of these patients., Methods: Twenty consecutive existing patients with DM being followed up at the Rheumatology Clinic of Kwong Wah Hospital, Hong Kong were recruited. Twenty patients with PM were recruited from the same clinic as the controls. A commercial line blot immunoassay was used to detect the anti-MDA5 Ab in all the participants. The frequencies of anti-MDA-5 Ab in the two groups were compared. The clinical characteristics of the patients with and without the antibody were analyzed., Results: Anti-MDA5 Ab was found in 30% of patients with DM but not in patients with PM. All patients with the antibody exhibited the clinically amyopathic DM (CADM) phenotype. These patients were predominantly male, younger and with shorter disease duration. Anti-MDA5 Ab was significantly associated with rapidly progressive interstitial lung disease (RP-ILD) and digital ulcers. No statistically significant association was found between other disease or treatment variables and the antibody., Conclusion: Anti-MDA5 Ab is found exclusively in DM patients of the CADM subtype and is associated with RP-ILD and digital ulcers, suggesting that examination of this antibody is clinically useful in Hong Kong Chinese patients with idiopathic inflammatory myopathies. However, further studies are required to assess its prognostic significance, and to explore the difference of its presentations in various populations., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: We aimed to examine the levels of serum H4 and activated protein C (APC) in rheumatoid arthritis (RA) and other autoimmune conditions, and investigate the associations between H4 or APC levels and disease activity indicators in RA., Methods: Serum H4 and APC distribution was examined in samples from patients with RA, systemic lupus erythematosus (SLE), polymyositis (PM), and ankylosing spondylitis (AS), as well as in samples from healthy controls, using commercial ELISA kits. Associations of serum H4 or APC levels with disease variables in patients with RA were evaluated. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminant capacity of APC against RA and non-RA., Results: The patients with RA, PM, and AS showed higher serum levels of H4 and APC than those from the healthy control individuals, while the SLE patients showed higher serum levels of APC only. Moderate positive correlations between H4 levels and absolute neutrophil count (ANC), platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), brinogen (FIB), D-dimer (DD), and complement fraction 3 (C3) were observed. Positive correlations between APC levels and PLT, RF, DD, or DAS28 were additionally found. ROC curve analysis revealed that APC discriminated well between RA and non-RA., Conclusions: H4 and APC concentrations are elevated in patients with chronic in ammatory autoimmune diseases. The observed associations between H4 and APC and disease variables in patients with RA support a role for H4 and APC in the in ammatory process of the disease.

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.

Recent studies have suggested that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR) are emerging markers of disease activity and prognosis in patients with chronic inflammatory diseases, cardiovascular diseases, or malignancies. Therefore, we investigated the clinical significance and prognostic value of the NLR and CAR in adult patients with polymyositis and dermatomyositis. The medical records of 197 patients with newly diagnosed polymyositis/dermatomyositis between August 2003 and November 2016 were retrospectively reviewed. Survival and causes of death were recorded during an average 33-month observational period. Clinical and laboratory findings were compared between survivors and non-survivors. Using receiver operating characteristic curves, the NLR and CAR cut-off values for predicting survival were calculated. Univariate and multivariate analyses using Cox proportional hazard models were performed to identify factors associated with survival. Twenty-six patients (13.2%) died during the study period, and the 5-year survival-rate was estimated to be 82%. The non-survivor group exhibited older age and a higher prevalence of interstitial lung disease (ILD), acute interstitial pneumonia, and acute exacerbation of ILD compared to that in the survivor group. NLR and CAR values were significantly higher in the non-survivors and in patients with polymyositis/dermatomyositis-associated ILD, and the death rates increased across NLR and CAR quartiles. Furthermore, when stratified according to the NLR or CAR optimal cut-off values, patients with a high NLR (>4.775) or high CAR (>0.0735) had a significantly lower survival rate than patients with low NLR or CAR, respectively. In addition, old age (>50 years), the presence of acute interstitial pneumonia, hypoproteinemia (serum protein <5.5 g/dL), and high NLR (but not high CAR) were independent predictors for mortality. The results indicate that a high NLR is independently associated with worse overall survival. Thus, the baseline NLR level may be a simple, cost-effective prognostic marker in patients with polymyositis/dermatomyositis.

Objective: The objective of this study is to elucidate predictors of relapse in patients with polymyositis and dermatomyositis (PM/DM)., Methods: Fifty PM/DM patients who achieved disease stabilization at Okayama University Hospital in 2004-2014 were enrolled retrospectively. Candidate predictors such as demographic factors, clinical symptoms, laboratory data, and treatment status were compared., Results: The mean age of enrolled patients was 58 years; 34 were female. The patient groupings were as follows: 21 with PM, 27 with DM, and two with clinically amyopathic DM. During a mean observation period of 685 d, 5 patients (10%) died and 20 (40%) relapsed. The relapsed patients displayed baseline muscle weakness less frequently (85% versus 100%, p = .03) and anti-SS-A/Ro antibody more frequently (65% versus 27%, p = .007). Anti-SS-A/Ro-positive patients exhibited a higher relapse rate than anti-SS-A/Ro-negative patients (log-rank test, p = .03). Anti-SS-A/Ro-positive patients also exhibited higher anti-Jo-1 antibody positivity and lower levels of serum complement. After adjusting anti-Jo-1 antibody positivity, age, sex, CK <500 IU/L, and lung involvement, anti-SS-A/Ro positivity was still an independent risk factor for higher relapse-rate (odds ratio, 5.5; 95% confidence interval, 1.4-25.1)., Conclusions: Anti-SS-A/Ro antibody positivity may be a useful biomarker for prediction of relapse.

Background: There are scarce studies in the literature about hyaluronic acid in systemic autoimmune myopathies., Objectives: To analyze the serum level of hyaluronic acid in patients with dermatomyositis and polymyositis., Methods: Cross-sectional study, single-center, that evaluated hyaluronic acid in 18 dermatomyositis and 15 polymyositis (Bohan and Peter criteria), newly diagnosed, with clinical and laboratory activity, with no previous drug treatment. The patients were also age-, gender- and ethnicity-matched to 36 healthy individuals. The hyaluronic acid was analyzed by ELISA/EIA kit anti-hyaluronic acid., Results: There was a higher serum level of hyaluronic acid in patients with autoimmune myopathies, in relation to control group (P<0.05). Moreover, the serum level of this glycosaminoglycan was higher in dermatomyositis, when compared to polymyositis. Both groups were comparable with regard to demographic, clinical and laboratory data, except for the presence of skin lesions in the first group., Study Limitations: The presence of hyaluronic acid in cutaneous lesions, particularly of patients with dermatomyositis, was not analyzed neither quantified. In addition, due to disease rarity and the establishment of strict inclusion and exclusion criteria, there was a small sample in the present study., Conclusions: As an example of others systemic autoimmune diseases, it is possible that the hyaluronic acid is involved in the pathogenesis of autoimmune myopathies, and particularly when associated with cutaneous lesions.

Background: The aim of this study was to compare the heterogeneity of interstitial lung disease (ILD) in patients with polymyositis and dermatomyositis (PM/DM) according to serological type., Methods: A total of 182 patients with PM/DM-ILD were observed retrospectively. Antiaminoacyl-tRNA synthetase (ARS) and antimelanoma differentiation-associated gene5 (MDA5) antibodies were screened using immunoblotting approach. The patients with ILD were divided into 3 groups: MDA5 (with anti-MDA5 antibody), ARS (with anti-ARS antibody) and MSN (without anti-MDA5 or anti-ARS antibody) group. Pulmonary features, treatment responses and prognoses were compared among the groups., Results: A higher percentage of rapidly progressive ILD (RP-ILD) occurrences (55.8% versus 25% versus 16.9%, P < 0.001) was observed in the MDA5 group compared to ARS and MSN groups. The MSN group experienced lower dyspnea (48.2% versus 79% versus 71.4%, P = 0.001) and fever (18.1% versus 39.5% versus 37.5%, P = 0.01) frequencies compared to MDA5 and ARS groups. Response to 6-month treatment among 95 patients showed highest deterioration ratio (70%, P = 0.001) of ILD in the MDA5 group. Additionally, the highest frequency of ILD improvement (60%, P = 0.04) was observed in the ARS group. During the observation period, 24 patients died of respiratory failure. The 5-year survival rates were significantly lower in MDA5 group (50.2%) compared to ARS group (97.7%) or the MSN group (91.4%) (P < 0.001)., Conclusions: MDA5-ILD was associated with severe pulmonary manifestations, poor response to treatment and aggravated prognosis. The ARS-ILD group had favorable treatment response and prognosis. MSN-ILD patients had relatively worse treatment response and prognosis compared to the ARS group, even though they expressed milder pulmonary manifestation., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies indicated that both red blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) were useful indices in assessing the disease activity of autoimmune diseases. However, the evidence for the association between RDW, NLR and dermatomyositis (DM) and polymyositis (PM) is limited. The aim of this study is to investigate the association between the disease activity of PM/DM and both RDW and NLR., Methods: Medical records of 114 PM/DM patients and 114 healthy controls were retrospectively reviewed, and their RDW, NLR and myositis disease activity assessment visual analogue scale (MYOACT) on admission were extracted. The correlations between RDW, NLR and MYOACT were analyzed using the Spearman approach and multivariable model., Results: PM/DM patients had significantly higher RDW and NLR. Increased RDW in PM/DM patients was not completely attributed to decreased hemoglobin or therapeutic agents. Both RDW and NLR are independently and positively correlated MYOACT., Conclusion: Both RDW and NLR are useful indices in assessing the disease activity of PM/DM., (© 2017 Wiley Periodicals, Inc.)

Objective: To examine the expression of chemokine receptors in different peripheral blood T-cell subsets in patients with polymyositis (PM) and dermatomyositis (DM)., Methods: We used flow cytometry to measure the frequencies of chemokinereceptors CXCR3 and CCR4 expression in the CD4 + or CD8 + lymphocytes. Enzyme linked immunosorbent assays were also used to measure the concentrations of C-X-C motif chemokine 10 (CXCL10), thymus and activation regulated chemokine (TARC) and macrophage derived chemokine (MDC)., Results: Comparing to 20 healthy controls, %CD4 + CXCR3 + and %CD8 + CXCR3 + T cells significantly decreased in 33DM patients, and %CD8 + CXCR3 + cells decreased in 24PM patients, but %CD4 + CCR4 + and %CD8 + CCR4 + cells did not significantly change in both the PM and DM patients. Accordingly, the Th1/Th2 polarization, analyzed as the balance obtained after dividing %CD4 + CXCR3 + cells by %CD4 + CCR4 + cells, showed a significant reduction in DM. The serum concentration of CXCR3 + ligand, CXCL10, significantly increased and negatively correlated with circulating %CD4 + CXCR3 + cells in DM patients. There was no significant change of TARC and MDC in PM and DM patients. Furthermore, %CD4 + CXCR3 + cells decreased more severely in the patients with interstitial lung disease., Conclusions: The present results indicate that the distributions of circulating CXCR3 + T-cells differ among the PM and DM cases. Our findings suggest a pathogenic difference between PM and DM., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The immunopathologic mechanism underlying dermatomyositis (DM) and polymyositis (PM) remains poorly understood. Many cytokines play a pathogenic role in DM and PM. Interleukin 21 (IL-21) has a pleiotropic effect on inflammation regulation. This study aimed to detect the serum IL-21 level and investigate the expression of IL-21 and IL-21 receptor (IL-21R) in muscle tissues of patients with DM and PM., Methods: Biopsied muscle samples were obtained from 11 patients with DM, 12 with PM, and six controls; mRNA levels of IL-21 and IL-21R were analyzed by real-time quantitative reverse transcription-polymerase chain reaction; and immunohistochemical staining was used to evaluate the protein expression of IL-21 and IL-21R. Serum samples were obtained from 36 patients with DM, 19 with PM, and 20 healthy controls. The serum IL-21 level was detected by enzyme-linked immunosorbent assay., Results: The expression of IL-21 was upregulated in patients with DM and PM. The IL-21 mRNA level was significantly increased in muscle tissues of patients with DM and PM (DM vs. control, P= 0.001; PM vs. control, P= 0.001), whereas IL-21R mRNA level in patients with DM/PM was not statistically different from that of healthy controls. Immunohistochemical staining showed both IL-21 and IL-21R were significantly expressed in the inflammatory cells in muscle tissues of patients with DM and PM. The serum IL-21 level was also significantly higher in patients with DM/PM than in controls (DM vs. control, 49.12 [45.28, 60.07] pg/ml vs. 42.54 [38.69, 48.85] pg/ml, P= 0.001; PM vs. control, 50.77 [44.19, 60.62] pg/ml vs. 42.54 [38.69, 48.85] pg/ml, P= 0.005)., Conclusions: IL-21 expression is upregulated in patients with DM and PM in both muscle tissue and serum. In addition, IL-21R protein is highly expressed in affected muscle tissues of patients with DM and PM. IL-21 may play a pathogenic role through IL-21R in patients with DM and PM.

Peripheral blood T lymphocytopenia has previously been identified in polymyositis/dermatomyositis (PM/DM) patients. Therefore, the present study aimed to examine the potential role of autophagy in peripheral blood T cell survival in PM/DM patients. Transmission electron microscopy was used to detect the formation of autophagosomes of peripheral blood cluster of differentiation (CD)3+ T cells obtained from 24 patients with PM/DM and 21 healthy controls. Protein and mRNA expression levels of autophagy‑related molecules were examined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction, respectively. The number of peripheral blood CD3+ T cells decreased significantly in PM/DM patients. The median percentage of apoptosis of CD3+ T cells in PM/DM patients was significantly increased compared with healthy controls. Furthermore, the number of autophagosomes and the expression of the autophagy markers microtubule‑associated protein 1A/1B‑light chain 3 (LC3) and Beclin‑1 were significantly reduced in the circulating CD3+ T cells of PM/DM patients compared with those of healthy controls. LC3 and Beclin‑1 protein levels correlated negatively with apoptosis rates in circulating CD3+ T cells in patients with PM/DM. CD3+ T cells from PM/DM patients treated with rapamycin increased autophagy and decreased apoptosis compared with untreated cells (P<0.05). In conclusion, these results suggested that autophagy may serve a potential protective role in the peripheral blood T cells of patients with PM/DM.

Objective: Oxidative stress and variations in antioxidant status are implicated in the pathogenesis of inflammatory and autoimmune diseases. Polymyositis and dermatomyositis (PM/DM) are autoimmune diseases with inflammatory cells infiltrating into skeletal muscles, and the antioxidant status is still controversial. The aim of our study was to investigate the correlation between PM/DM and the antioxidant status of serum bilirubin (Tbil, Dbil and Ibil) and uric acid (UA)., Materials and Methods: We measured serum concentrations of bilirubin (Tbil, Dbil and Ibil) and uric acid in 384 individuals, including 110 PM/DM patients and 274 healthy controls., Results: We found that PM/DM patients had significantly lower serum concentrations of bilirubin (Tbil and Ibil) and uric acid than healthy controls, whether male or female. Also, after separately adjusting the covariances of age and gender, Tbil, Dbil, Ibil and UA were all relevant factors for PM/DM. Moreover, there were no significant differences in serum antioxidant molecule levels between PM and DM subgroups., Conclusion: Our study demonstrated the low serum levels of bilirubin and uric acid in patients with PM/DM. This suggested low antioxidant status in PM/DM patients with excessive oxidative stress.

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.

This study aimed at analyzing published data on the association between idiopathic inflammatory myopathy and venous thromboembolism (VTE). We examined studies on VTE risk in patients with polymyositis (PM) and/or dermatomyositis (DM), in the MEDLINE, EMBASE, and Cochrane databases and via manual searches. We performed a meta-analysis on the relative risks (RRs) of VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) in these patients. Five studies, including 8858 patients with PM/DM met the inclusion criteria. Meta-analysis revealed a significant association between PM/DM and VTE risk (RR = 4.364, 95% CI 2.128-8.949, p = 5.8 × 10 -5 ). A significant association was found between PE risk and PM/DM (RR = 3.504, 95% CI 2.856-4.300, p < 1.0 × 10 -8 ). Meta-analysis also indicated a significant association between DVT risk and PM/DM (RR = 7.481, 95% CI 3.355-16.68, p = 8.7 × 10 -7 ). This meta-analysis demonstrated that both types of PM/DM are associated with an elevated risk of VTE, PE, and DVT, suggesting that patients with PM/DM should be carefully monitored for development of these conditions.

Objective: To characterize patients with myositis with HIV infection., Methods: All HIV-positive patients with myositis seen at the Johns Hopkins Myositis Center from 2003 to 2013 were included in this case series. Muscle biopsy features, weakness pattern, serum creatine kinase (CK) level, and anti-nucleotidase 1A (NT5C1A) status of HIV-positive patients with myositis were assessed., Results: Eleven of 1,562 (0.7%) patients with myositis were HIV-positive. Myositis was the presenting feature of HIV infection in 3 patients. Eight of 11 patients had weakness onset at age 45 years or less. The mean time from the onset of weakness to the diagnosis of myositis was 3.6 years (SD 3.2 years). The mean of the highest measured CK levels was 2,796 IU/L (SD 1,592 IU/L). On muscle biopsy, 9 of 10 (90%) had endomysial inflammation, 7 of 10 (70%) had rimmed vacuoles, and none had perifascicular atrophy. Seven of 11 (64%) patients were anti-NT5C1A-positive. Upon presentation, all had proximal and distal weakness. Five of 6 (83%) patients followed 1 year or longer on immunosuppressive therapy had improved proximal muscle strength. However, each eventually developed weakness primarily affecting wrist flexors, finger flexors, knee extensors, or ankle dorsiflexors., Conclusions: HIV-positive patients with myositis may present with some characteristic polymyositis features including young age at onset, very high CK levels, or proximal weakness that improves with treatment. However, all HIV-positive patients with myositis eventually develop features most consistent with inclusion body myositis, including finger and wrist flexor weakness, rimmed vacuoles on biopsy, or anti-NT5C1A autoantibodies., (© 2017 American Academy of Neurology.)

Objectives: We aimed to identify the possible clinical and laboratory predictors of calcinosis in a cohort of patients with a diagnosis of polymyositis (PM) and dermatomyositis (DM)., Methods: We carried out a retrospective analysis of a cohort of myositis patients attending our clinic between January 2013 and May 2014., Results: 74 patients (58 females, 16 males) with PM (30 cases), DM (30 cases), overlap syndrome (13 cases) and inclusion body myositis (1 case) were enrolled. Sixteen patients (21.6%) had calcinosis that occurred a mean of 43.7 months after diagnosis of PDM. At multivariate analysis, patients with calcinosis experienced longer follow-up duration (p=0.006), anti-PM/Scl (p=0.033) and anti-NXP2 (p=0.024) positivity compared to patients without calcinosis. Furthermore, anti-NXP-2 positive C+ showed a diffuse form of calcinosis from the beginning and lower frequency of respiratory tract involvement. No single drug or associations of drugs was found effective in the treatment of calcinosis., Conclusions: A longer follow-up period of time, DM diagnosis and positivity for PM/Scl and NXP-2 could all be considered risk factors which foresee the development of calcinosis. Moreover, the positivity for antibodies to NXP-2 depicts a distinct phenotype of calcinosis with an early onset and quick widespread dissemination.

This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their association with cancer. Sera from 40 patients with polymyositis, dermatomyositis, and controls were tested by protein and RNA immunoprecipitation to detect autoantibodies, and immunoprecipitation-Western blot was used for anti-MJ/NXP-2, anti-MDA5, and anti-TIF1γ/α identification. Medical records were re-evaluated with specific focus on cancer. Anti-MJ/NXP-2 and anti-TIF1γ/α were the most common antibodies in dermatomyositis. In six dermatomyositis cases, we found five solid forms of cancer and one Hodgkin's lymphoma in long-term remission. Among patients with cancer-associated dermatomyositis, three were positive for anti-TIF1γ/α, two for anti-Mi-2, and one for anti-MJ/NXP-2. The strongest positivity of anti-TIF1γ was seen in two active forms of cancer, and this antibody was either negative or positive at low titers in the absence of cancer or in the 7-year remission Hodgkin's lymphoma. Four out of twenty (20 %) patients with polymyositis had solid cancer, but no specific association with autoantibodies was identified; further, none of the four cases of antisynthetase syndrome had a history of cancer. No serum myositis-associated autoantibody was observed in control sera, resulting in positive predictive value 75 %, negative predictive value 78.5 %, sensitivity 50 %, specificity 92 %, and area under the ROC curve 0.7083 for the risk of paraneoplastic DM in anti-TIF1γ/α (+) patients. Myositis-specific autoantibodies can be identified thanks to the use of immunoprecipitation, and their association with cancer is particularly clear for anti-TIF1γ/α in dermatomyositis. This association should be evaluated in a prospective study by immunoprecipitation in clinical practice.