Association between clinical phenotypes of dermatomyositis and polymyositis with myositis-specific antibodies and overlap systemic autoimmune diseases.

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.

Interleukin-35 in idiopathic inflammatory myopathies.

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.

Reduced miR-146a Promotes REG3A Expression and Macrophage Migration in Polymyositis and Dermatomyositis.

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.

Interleukin-35: A Serological Biomarker for Patients with Polymyositis/Dermatomyositis.

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.

Clinical significance of myositis-specific autoantibody profiles in Japanese patients with polymyositis/dermatomyositis.

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.

Serum KL-6 is associated with the severity of interstitial lung disease in Chinese patients with polymyositis and dermatomyositis.

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.

Serum-soluble TRAIL: a potential biomarker for disease activity in myositis patients.

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.

Effect of CTLA4-Ig (abatacept) treatment on T cells and B cells in peripheral blood of patients with polymyositis and dermatomyositis.

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.

MicroRNA-381 reduces inflammation and infiltration of macrophages in polymyositis via downregulating HMGB1.

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.

Giant Cell Polymyositis and Myocarditis in a Patient With Thymoma and Myasthenia Gravis: A Postviral Autoimmune Process?

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 effect of cigarette smoking on the clinical and serological phenotypes of polymyositis and dermatomyositis.

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.

Hyaluronic acid in dermatomyositis and polymyositis: relationship with disease and cutaneous lesions

Abstract: 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.

Baseline peripheral blood neutrophil-to-lymphocyte ratio could predict survival in patients with adult polymyositis and dermatomyositis: A retrospective observational study.

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.

Analysis of anti-melanoma differentiation-associated gene 5 antibody in Hong Kong Chinese patients with idiopathic inflammatory myopathies: diagnostic utility and clinical correlations.

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.

Clinical Heterogeneity of Interstitial Lung Disease in Polymyositis and Dermatomyositis Patients With or Without Specific Autoantibodies.

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.

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

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

Patients with pure dermatomyositis/polymyositis and anti-PM/Scl autoantibody resembling anti-synthetase syndrome / Pacientes com dermatomiosite/polimiosite pura e autoanticorpo anti-pm/scl sememlhante à síndrome anti-sintetase

OBJECTIVE: The anti-PM/Scl autoantibody has been described in patients with scleromyositis. However, there are scant studies evaluating its prevalence and reactivity in dermatomyositis and polymyositis. METHOD: A cross-sectional, single center study evaluating the anti-PM/Scl autoantibody in 85 dermatomyositis and 32 polymyositis patients, without overlapping syndrome, was conducted between 2000 and 2016. Clinical data and complementary examinations were reviewed from electronic medical records with pre-parameterized information. RESULTS: The mean age of dermatomyositis and polymyositis patients was 41.1 and 42.8 years, respectively. The presence of anti-PM/Scl was observed in 5 (5.9%) dermatomyositis and 2 (6.3%) polymyositis patients. Two of these patients also had the anti-Ku antibody. The relevant clinical manifestations of these 7 patients were constitutional symptoms (100% of cases), muscular (100%), pulmonary (85.7%) and joint (71.4%) involvement, "mechanic hands" (85.7%), Raynaud phenomenon (85.7%) and plantar hyperkeratosis (85.7%). The 7 patients had relapses of disease activity, but at conclusion of the present study, 5 had complete clinical response and 2 complete remission of the disease. CONCLUSION: There is a low frequency of the anti-PM/Scl autoantibody in dermatomyositis and polymyositis patients. In addition, patients with this autoantibody exhibit a similar pattern of manifestations to that of antisynthetase syndrome.

OBJETIVO: O autoanticorpo anti-PM/Scl foi descrito em pacientes com escleromiosite. No entanto, há escassos estudos avaliando sua prevalência e reatividade em dermatomiosite (DM) e polimiosite (PM). MÉTODOS: Estudo transversal, num único centro, que avaliou o autoanticorpo anti-PM/Scl em 85 DM e 32 PM, sem síndrome de sobreposição, no período entre 2000 e 2016. Os dados clínicos e os exames complementares foram revisados a partir de registros médicos eletrônicos com informações pré-parametrizadas. RESULTADOS: A média de idade dos pacientes com DM e PM foi, respectivamente, de 41,1 e 42,8 anos. A presença de anti-PM/Scl foi observada em 5 (5,9%) DM e 2 (6,3%) pacientes com PM. Dois desses pacientes também possuíam o anticorpo anti-Ku. As manifestações clínicas relevantes desses 7 pacientes foram sintomas constitucionais (100% dos casos), envolvimento muscular (100%), pulmonar (85,7%) e articular (71,4%), "mãos mecânicas" (85,7%), fenômeno de Raynaud (85,7 %) e hiperqueratose plantar (85,7%). Os 7 pacientes apresentaram recidivas da atividade da doença, mas, no final do presente estudo, 5 apresentaram resposta clínica completa e 2 remissões completas da doença. CONCLUSÃO: Há uma baixa freqüência do autoanticorpo anti-PM/Scl em pacientes com DM e PM. Além disso, os pacientes com este autoanticorpo apresentam um padrão semelhante de manifestações para a síndrome da antisintetase.

Overlapping features of polymyositis and inclusion body myositis in HIV-infected patients.

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.

Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease.

BACKGROUND: Macrophage activation is involved in the pathogenesis of polymyositis (PM)/dermatomyositis (DM). CD163, a scavenger receptor expressed on the surface of activated macrophages, mediates anti-inflammatory functions. This study aimed to evaluate the clinical significance of soluble CD163 (sCD163) in PM/DM-related interstitial lung disease (ILD). METHODS: The main subjects were 48 patients with PM/DM-related ILD. As controls, 10 patients with PM/DM without ILD and 20 healthy volunteers were enrolled. In patients with PM/DM-related ILD, the baseline characteristics and clinical course were obtained through a review of patient medical records. Serum sCD163 levels at ILD diagnosis were quantified by enzyme-linked immunosorbent assay, which were compared with the other baseline clinical factors and evaluated for potential as a prognostic biomarker. In addition, immunohistochemistry analysis using anti-human CD163 antibody was performed on the lung sections of two patients with DM-related ILD (a survivor and non-survivor, respectively) and one patient with early-stage lung cancer as a normal control. RESULTS: The median value of serum sCD163 in patients with PM/DM-related ILD was 818 ng/mL, which was higher than that of PM/DM patients without ILD and healthy volunteers (716 ng/mL and 340 ng/mL, respectively). Significant but mild correlations with serum sCD163 levels were observed for serum C-reactive protein levels (r = 0.322) and % predicted forced vital capacity (r = -0.301) in patients with PM/DM-related ILD. A Cox proportional hazard model demonstrated that patients with PM/DM-related ILD and higher sCD163 levels had worse prognosis (age-adjusted and gender-adjusted hazard ratio per 100 ng/mL increase 1.27, 95% confidence interval 1.11-1.45, P <0.001). In immunohistochemistry analysis, compared with normal lung, alveolar infiltration of CD163-positive macrophages was evident in the lungs of patients with DM-related ILD. Especially, the finding was more severe in the non-survivor's lung. CONCLUSIONS: Serum sCD163 might be a potential biomarker for predicting the severity and prognosis of PM/DM-related ILD. Our results suggest the importance of macrophage activation in the disease.