Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies.

Muscle cell death in polymyositis is induced by CD8+ cytotoxic T lymphocytes. We hypothesized that the injured muscle fibers release pro-inflammatory molecules, which would further accelerate CD8+ cytotoxic T lymphocytes-induced muscle injury, and inhibition of the cell death of muscle fibers could be a novel therapeutic strategy to suppress both muscle injury and inflammation in polymyositis. Here, we show that the pattern of cell death of muscle fibers in polymyositis is FAS ligand-dependent necroptosis, while that of satellite cells and myoblasts is perforin 1/granzyme B-dependent apoptosis, using human muscle biopsy specimens of polymyositis patients and models of polymyositis in vitro and in vivo. Inhibition of necroptosis suppresses not only CD8+ cytotoxic T lymphocytes-induced cell death of myotubes but also the release of inflammatory molecules including HMGB1. Treatment with a necroptosis inhibitor or anti-HMGB1 antibodies ameliorates myositis-induced muscle weakness as well as muscle cell death and inflammation in the muscles. Thus, targeting necroptosis in muscle cells is a promising strategy for treating polymyositis providing an alternative to current therapies directed at leukocytes.

Fatal disseminated Anncaliia algerae myositis mimicking polymyositis in an immunocompromised patient.

We report the first New Zealand case of Anncaliia algerae myositis in a 55-year-old man with a history of psoriatic arthritis, treated with long-term immunosuppressive therapy. He resided in the city of Rotorua, which is famous for geothermal hot springs. A vastus lateralis muscle biopsy was performed to investigate the cause of an unexplained myositis. Light microscopy demonstrated a necrotizing myositis with scattered clusters of ovoid spores within the myocyte cytoplasm resembling microsporidia. DNA analysis by PCR and electron microscopy confirmed microsporidial myositis with features characteristic of A. algerae. Immunosuppressive drugs were stopped and the patient was treated with cholestyramine wash and albendazole. The patient deteriorated with involvement of bulbar and respiratory muscles requiring intensive care and ventilation. He died 3 weeks after diagnosis. Post-mortem examination of skeletal muscle from tongue and intercostal muscles also revealed numerous organisms confirming disseminated disease.

Chest pain in a mid-aged woman, not simply myopericarditis: a case report of anti-Ku positive polymyositis.

BACKGROUND: Anti-Ku is a rare antibody which can be positive in some rheumatic diseases and it might be related to cardiac involvement. Polymyositis is an inflammatory myopathy, and its cardiac involvement seldom presents as myopericarditis and anti-Ku positive. CASE PRESENTATION: In this case, we report a mid-aged woman with chest pain, upper limbs weakness and fever unrelated with infection. The diagnosis of this case was unquestionably myopericarditis supported by ECG, cardiac MRI and negative findings in coronary arteries. Diagnosis of polymyositis was further clarified by the evidence of persistently increased CK, degeneration of proximal muscle in MRI, muscular dystrophy with lymphocytes infiltration in muscle biopsy. In the analysis of autoantibodies, we surprisingly discovered positive anti-Ku. Glucocorticoid and mycophenolate mofetil were then prescribed for polymyositis. Patient follow-up indicated remission of both myopericarditis and polymyositis. We finally clarified this rare case as a positive anti-Ku polymyositis with myopericarditis as cardiac involvement. CONCLUSION: This report presents a rare case with anti-Ku positive polymyositis and the cardiac involvement of polymyositis was manifested as myopericarditis. Therefore, positive anti-Ku might explain the myopericarditis as cardiac involvement in polymyositis. More cases and longer duration of follow-up is required for the comprehensive understanding of the disease.

Pathology Features of Immune and Inflammatory Myopathies, Including a Polymyositis Pattern, Relate Strongly to Serum Autoantibodies.

We asked whether myopathology features of immune or inflammatory myopathies (IIM), without reference to clinical or laboratory attributes, correlate with serum autoantibodies. Retrospective study included 148 muscle biopsies with: B-cell inflammatory foci (BIM), myovasculopathy, perimysial pathology (IMPP), myofiber necrosis without perimysial or vessel damage or inflammation (MNec), inflammation and myofiber vacuoles or mitochondrial pathology (IM-VAMP), granulomas, chronic graft-versus-host disease, or none of these criteria. 18 IIM-related serum autoantibodies were tested. Strong associations between myopathology and autoantibodies included: BIM with PM/Scl-100 (63%; odds ratio [OR] = 72); myovasculopathies with TIF1-γ or NXP2 (70%; OR = 72); IMPP with Jo-1 (33%; OR = 28); MNec with SRP54 (23%; OR = 37); IM-VAMP with NT5C1a (95%; OR = 83). Hydroxymethylglutaryl-CoA reductase (HMGCR) antibodies related to presence of myofiber necrosis across all groups (82%; OR = 9), but not to one IIM pathology group. Our results validate characterizations of IIM by myopathology features, showing strong associations with some serum autoantibodies, another objective IIM-related marker. BIM with PM/Scl-100 antibodies can be described pathologically as polymyositis. Tif1-γ and NXP2 antibodies are both common in myovasculopathies. HMGCR antibodies associate with myofiber necrosis, but not one IIM pathology subtype. Relative association strengths of IIM-related autoantibodies to IIM myopathology features versus clinical characteristics require further study.

Texture analysis of muscle MRI: machine learning-based classifications in idiopathic inflammatory myopathies.

To develop a machine learning (ML) model that predicts disease groups or autoantibodies in patients with idiopathic inflammatory myopathies (IIMs) using muscle MRI radiomics features. Twenty-two patients with dermatomyositis (DM), 14 with amyopathic dermatomyositis (ADM), 19 with polymyositis (PM) and 19 with non-IIM were enrolled. Using 2D manual segmentation, 93 original features as well as 93 local binary pattern (LBP) features were extracted from MRI (short-tau inversion recovery [STIR] imaging) of proximal limb muscles. To construct and compare ML models that predict disease groups using each set of features, dimensional reductions were performed using a reproducibility analysis by inter-reader and intra-reader correlation coefficients, collinearity analysis, and the sequential feature selection (SFS) algorithm. Models were created using the linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), support vector machine (SVM), k-nearest neighbors (k-NN), random forest (RF) and multi-layer perceptron (MLP) classifiers, and validated using tenfold cross-validation repeated 100 times. We also investigated whether it was possible to construct models predicting autoantibody status. Our ML-based MRI radiomics models showed the potential to distinguish between PM, DM, and ADM. Models using LBP features provided better results, with macro-average AUC values of 0.767 and 0.714, accuracy of 61.2 and 61.4%, and macro-average recall of 61.9 and 59.8%, in the LDA and k-NN classifiers, respectively. In contrast, the accuracies of radiomics models distinguishing between non-IIM and IIM disease groups were low. A subgroup analysis showed that classification models for anti-Jo-1 and anti-ARS antibodies provided AUC values of 0.646-0.853 and 0.692-0.792, with accuracy of 71.5-81.0 and 65.8-78.3%, respectively. ML-based TA of muscle MRI may be used to predict disease groups or the autoantibody status in patients with IIM and is useful in non-invasive assessments of disease mechanisms.

Multiple neurological manifestations in a patient with systemic lupus erythematosus and anti-NXP2-positive myositis: A case report.

RATIONALE: Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory disease that frequently affects various organs. Neuropsychiatric manifestations in SLE patients, known as neuropsychiatric SLE, are clinically common. However, the principal manifestation of cranial neuropathy in patients with SLE and comorbidities is relatively rare. PATIENT CONCERNS: In this report, we describe a 51-year-old Chinese woman who was admitted with a chief complaint of chronic-onset facial paresthesia, dysphagia, and choking cough when drinking water, accompanied by slurred speech, salivation, and limb weakness. The blood autoantibody test results showed that many SLE-associated antibodies were positive. Meanwhile, anti-nuclear matrix protein 2 (NXP2) antibody was strongly positive in the idiopathic inflammatory myopathy (IIM) spectrum test from the serum. Muscle biopsy indicated inflammatory infiltration of the muscle fiber stroma. DIAGNOSES: Taking into account the clinical manifestations and laboratory tests of the present case, the diagnosis of SLE and probable IIM was established. INTERVENTIONS: Corticosteroids and additional gamma globulin were administered and the clinical symptoms were relieved during the treatment process. OUTCOMES: Unfortunately, the patient experienced sudden cardiac and respiratory arrest. Multiple system dysfunctions exacerbated disease progression, but in the present case, we speculated that myocardial damage resulting from SLE could explain why she suddenly died. LESSONS: To our knowledge, multiple neurological manifestations in patients with SLE and anti-NXP2-positive myositis are rare. Note that SLE is still a life-threatening disease that causes multiple system dysfunctions, which requires increasing attention.

Polymyositis: is there anything left? A retrospective diagnostic review from a tertiary myositis centre.

OBJECTIVE: The current classification criteria for idiopathic inflammatory myopathy (IIM) retain PM as a major disease subgroup. However, evolution in the understanding of IIM has suggested that many of these patients could be better described as having an alternative diagnosis. In the present study, we apply the latest understanding of IIM subtyping to retrospectively review PM diagnoses in a large cohort of IIM patients. METHODS: Within a previously reported cohort of 255 patients from a UK tertiary myositis clinic, 37 patients classified as PM according to both the EULAR/ACR IIM criteria and expert opinion were identified. Clinical data and complementary tests were reviewed, and consensus decisions regarding final classification were reached in each case. RESULTS: Nine (9/37, 24.3%) patients remained classified as PM, 3.5% (9/255) of the original cohort; these PM patients were seronegative for myositis antibodies, responsive to immunosuppression, and in 4/7 (57.1%) patients where muscle biopsy was performed had HLA-1 upregulation and endomysial inflammatory infiltrates. Immune-mediated necrotizing myopathy (5/37, 13.5%) and connective tissue disease overlap myositis (7/37, 19%) were the main alternative diagnoses. The remaining patients were diagnosed as: unspecified myopathy (6/37, 16%), dermatomyositis (2/37, 5%), cancer-associated myopathy (3/37, 8.1%), and non-inflammatory myopathy (1/37, 3%, myofibrillar myopathy). Four patients (4/37, 10%) had insufficient data available to confidently reclassify. CONCLUSION: Our study confirms that PM can now be considered a rare IIM subgroup. A thorough examination, complete myositis autoantibody panel, and careful interpretation of the biopsy results is recommended to confirm the correct IIM sub-type.

Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD.

OBJECTIVES: To evaluate the efficacy and safety of ultra-low dose (100 mg) rituximab (RTX) administration in anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with polymyositis/dermatomyositis (PM/DM) associated interstitial lung disease. METHODS: This retrospective study included anti-MDA5 antibody positive ILD subjects in the First Affiliated Hospital of Guangzhou Medical University from November 2017 to March 2019. Independent predictors for 180-day mortality were measured by Cox regression analysis. Patients were divided into 3 groups: Group 1 (non-cyclophosphamide (CTX)/RTX) (n = 10), Group 2 (CTX only) (n = 19) and Group 3 (RTX with/without CTX) (n = 11). The 180-day mortality was compared among 3 groups with Kaplan-Meier analysis. Post-RTX serological parameters as well as adverse events were evaluated. RESULTS: Forty patients were included with the mean age of 51.3 years. Elevated IL-10 level and CD4+/8+ ratio were considered as risk factors of 180-day mortality. Kaplan-Meier analysis showed a trend toward decrease, albeit non-significant, in 180-day mortality in Group 3 (P = 0.26). The administration of 100 mg RTX brought down B cell within 7 days that lasted for 180 days. There were 7 and 6 infection events observed within 2 months of CTX/RTX treatment in Group 2 and 3, with 5 and 2 fatal cases respectively. Cytomegalovirus infection accounted for half infection events in Group 3. CONCLUSION: We found a pronounced and prolonged B cell depletion following 100 mg RTX infusion and RTX add-on may be effective in anti-MDA5 positive ILD patients. However, infection, especially opportunistic infection, should be concerned during the treatment.

Apoptosis in idiopathic inflammatory myopathies with partial invasion; a role for CD8+ cytotoxic T cells?

Polymyositis and inclusion body myositis are idiopathic inflammatory myopathies, with a pathology characterized by partial invasion of non-necrotic muscle fibres by CD8+ cytotoxic T-cells, leading to fibre degeneration. Although the main effector pathway of CD8+ T-cells is to induce apoptosis of target cells, it has remained unclear if apoptosis occurs in these diseases, and if so, if it is mediated by CD8+ T-cells. In consecutive biopsy sections from 10 patients with partial invasion, muscle fibres and inflammatory cells were assessed by immunohistochemistry and apoptotic nuclei by the TUNEL assay. Analysis of muscle fibre morphology, staining pattern and quantification were performed on digital images, and they were compared with biopsies from 10 dermatomyositis patients and 10 controls without muscle disease. Apoptotic myonuclei were found in muscle with partial invasion, but not in the invaded fibres. Fibres with TUNEL positive nuclei were surrounded by CD8+ T-cells, granzyme B+ cells and macrophages, but lacked FAS receptor expression. In contrast, apoptotic myonuclei were rare in dermatomyositis and absent in controls. The findings confirm that apoptosis occurs in idiopathic inflammatory myopathies and support that it is mediated by CD8+ cytotoxic T- cells, acting in parallel to the process of partial invasion.

High- density lipoprotein function is abnormal in idiopathic inflammatory myopathies.

OBJECTIVE: Damage to the vascular endothelium is strongly implicated in the pathogenesis of idiopathic inflammatory myopathies (IIM). Normally, high-density lipoprotein (HDL) protects the vascular endothelium from damage from oxidized phospholipids, which accumulate under conditions of oxidative stress. The current work evaluated the antioxidant function of HDL in IIM patients. METHODS: HDL's antioxidant function was measured in IIM patients using a cell-free assay, which assesses the ability of isolated patient HDL to inhibit oxidation of low-density lipoproteins and is reported as the HDL inflammatory index (HII). Cholesterol profiles were measured for all patients, and subgroup analysis included assessment of oxidized fatty acids in HDL and plasma MPO activity. A subgroup of IIM patients was compared with healthy controls. RESULTS: The antioxidant function of HDL was significantly worse in patients with IIM (n = 95) compared with healthy controls (n = 41) [mean (S.d.) HII 1.12 (0.61) vs 0.82 (0.13), P < 0.0001]. Higher HII associated with higher plasma MPO activity [mean (S.d.) 13.2 (9.1) vs 9.1 (4.6), P = 0.0006] and higher oxidized fatty acids in HDL. Higher 5-hydroxyeicosatetraenoic acid in HDL correlated with worse diffusion capacity in patients with interstitial lung disease (r = -0.58, P = 0.02), and HDL's antioxidant function was most impaired in patients with autoantibodies against melanoma differentiation-associated protein 5 (MDA5) or anti-synthetase antibodies. In multivariate analysis including 182 IIM patients, higher HII was associated with higher disease activity and DM diagnosis. CONCLUSION: The antioxidant function of HDL is abnormal in IIM patients and may warrant further investigation for its role in propagating microvascular inflammation and damage in this patient population.

Comparison of cytokine profiles between anti-ARS antibody-positive interstitial lung diseases and those with anti-MDA-5 antibodies.

INTRODUCTION/OBJECTIVES: Interstitial lung disease (ILD) is a significant cause of mortality among patients with dermatomyositis (DM) or polymyositis (PM). There are two subtypes of PM and DM often complicated with ILD: those with anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies and those with anti-MDA-5-associated amyopathic DM (ADM). Our aim is to clarify the inflammatory and immunological differences between the disorders. METHODS: We retrospectively collected consecutive patients with anti-ARS-ILD and those with anti-MDA-5 antibody-positive ADM-ILD. The serum concentration of 38 cytokines was measured using a cytokine panel. The relative risks for anti-MDA-5 antibody-positive ADM-ILD were examined with univariate and multivariate logistic regression models. Spearman's rank correlation coefficient was calculated between cytokine levels and clinical parameters in the disease. Levels of cytokines were compared between anti-ARS-ILD and anti-MDA-5-positive ADM-ILD patients (alive or dead) using Dunnett's test. RESULTS: Twenty-three patients with anti-ARS-ILD and the same number of patients with anti-MDA-5-positive ADM-ILD were enrolled. The anti-MDA-5 group had poor survival (p = 0.025). Univariate logistic regression models showed that eotaxin, IL-10, IP-10, and MCP-1 were associated with the diagnosis of anti-MDA-5-positive ADM-ILD. Multivariate logistic regression models revealed that IP-10 was the most significantly associated (p = 0.001). Relationship analyses showed that IL-10 had significant positive correlations with CK (r = 0.5267, p = 0.009) and ferritin (r = 0.4528, p = 0.045). A comparison of the cytokine levels found that IP-10 was elevated in both patients who were alive and patients who had died with ADM-ILD compared with the levels in those with ARS-ILD (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Anti-MDA-5-positive ADM-ILD had poorer survival than anti-ARS-ILD. IP-10 seems to be most deeply involved in the pathophysiology of anti-MDA-5-associated ADM-ILD.Key Points• To clarify differences in the inflammatory and immunological features of anti-MDA-5-positive ADM-ILD and anti-ARS-ILD, we performed an observational study to measure serum cytokine concentrations before treatment using a multiplex immunoassay system.• Multivariate logistic regression models revealed that IP-10 was associated with the most significant relative risk for ADM-ILD with anti-MDA-5 antibodies.• Levels of IP-10 were elevated considerably in anti-MDA-5-positive survivors and nonsurvivors compared with the levels in anti-ARS patients.• These results suggest that IP-10 is the most deeply involved in the pathophysiology of anti-MDA-5-positive ADM-ILD.

A new in vitro model of polymyositis reveals CD8+ T cell invasion into muscle cells and its cytotoxic role.

OBJECTIVES: The hallmark histopathology of PM is the presence of CD8+ T cells in the non-necrotic muscle cells. The aim of this study was to clarify the pathological significance of CD8+ T cells in muscle cells. METHODS: C2C12 cells were transduced retrovirally with the genes encoding MHC class I (H2Kb) and SIINFEKL peptide derived from ovalbumin (OVA), and then differentiated to myotubes (H2KbOVA-myotubes). H2KbOVA-myotubes were co-cultured with OT-I CD8+ T cells derived from OVA-specific class I restricted T cell receptor transgenic mice as an in vitro model of PM to examine whether the CD8+ T cells invade into the myotubes and if the myotubes with the invasion are more prone to die than those without. Muscle biopsy samples from patients with PM were examined for the presence of CD8+ T cells in muscle cells. The clinical profiles were compared between the patients with and without CD8+ T cells in muscle cells. RESULTS: Analysis of the in vitro model of PM with confocal microscopy demonstrated the invasion of OT-I CD8+ T cells into H2KbOVA-myotubes. Transmission electron microscopic analysis revealed an electron-lucent area between the invaded CD8+ T cell and the cytoplasm of H2KbOVA-myotubes. The myotubes invaded with OT-I CD8+ T cells died earlier than the uninvaded myotubes. The level of serum creatinine kinase was higher in patients with CD8+ T cells in muscle cells than those without these cells. CONCLUSION: CD8+ T cells invade into muscle cells and contribute to muscle injury in PM. Our in vitro model of PM is useful to examine the mechanisms underlying muscle injury induced by CD8+ T cells.

Identification of a novel autoantigen eukaryotic initiation factor 3 associated with polymyositis.

OBJECTIVES: To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. METHODS: Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren's syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. RESULTS: IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. CONCLUSION: We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

Biologic therapy in the idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases resulting from inflammation of muscle and manifesting as weakness, though a range of extra-muscular manifestations are observed. These are often correlated closely with disease subtype and the presence of myositis-specific/myositis-associated antibodies. IIM are notoriously difficult to treat and often refractory to glucocorticoid therapy and synthetic immunosuppressants. Both the innate and adaptive immune systems are implicated in the pathogenesis of IIM. A growing understanding of the key cytokines as well as the cell-mediated and antibody effectors of disease has identified multiple potential targets for biologic therapy. The most widely used of these is B-cell depletion via rituximab though the tumour necrosis factor inhibitors and other biologic therapies used in diseases such as rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis have also been trialled. This review summarises the literature thus far on biologic therapy in IIM, highlighting both the significant trials that influence current treatment regimens and also the continuing need for further research to inform more effective therapies.

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.

An Anti-PM/Scl-75 Antibody-positive Japanese Woman Who Developed Inflammatory Myopathy.

A 69-year-old Japanese woman presented with mild muscle weakness of the neck and symmetrical proximal parts of the upper and lower limbs. Laboratory tests, needle electromyography, and a muscle biopsy revealed inflammatory myopathy with an apparent clinical classification of polymyositis and positive findings for anti-PM/Scl-75 antibody. This antibody is rare among Japanese populations, and most Japanese patients with the antibody are not classified with the inflammatory myopathy seen in polymyositis. The muscle biopsy also showed marked necrotic and regenerative fibers. We need to collectively investigate patients with the potential to develop this disease, and to identify any unique characteristics for Asian populations, including Japanese.

Autophagy markers LC3 and p62 accumulate in immune-mediated necrotizing myopathy.

INTRODUCTION: The molecular mechanism of immune-mediated necrotizing myopathy (IMNM) remains unknown. Autophagy impairment, described in autoimmune diseases, is a key process in myofiber protein degradation flux and muscle integrity and has not been studied in IMNM. METHODS: Muscle biopsies from patients with IMNM (n = 40), dermatomyositis (DM; 24), polymyositis (PM; 8), polymyositis with mitochondrial pathology (4), sporadic inclusion body myositis (8), and controls (6) were compared by immunohistochemistry. RESULTS: The proportions of myofibers containing autophagy markers LC3b and p62 were higher in IMNM than in DM or PM and correlated with creatine kinase levels. In IMNM, compartmentalized LC3b puncta were located in regenerating and degenerating myofibers surrounded by major histocompatibility complex type II+ inflammatory cells. Several IMNM myofibers accumulated ubiquitin and misfolded protein. DISCUSSION: The detection of LC3b+ or p62+ myofibers could be used in differentiating IMNM from PM. The identification of autophagy-modifying molecules potentially could improve patients' outcomes. Muscle Nerve, 2019.

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.