Germinal centers are associated with postthymectomy myasthenia gravis in patients with thymoma.

BACKGROUND AND PURPOSE: Germinal centers (GCs) can be observed in the thymic tissues of patients with thymoma-associated myasthenia gravis (MG). Although an association between thymic GCs and MG has been suggested, it is unknown whether the presence of GCs could predict the development of MG after the resection of thymoma, known as postthymectomy MG. METHODS: We conducted a retrospective analysis of previously nonmyasthenic patients who underwent surgical removal of the thymoma. All available thymic tissue slides were rereviewed by a pathologist to assess for GCs. Patients were classified into GC-positive and GC-negative groups based on the presence of GCs. The incidence of postthymectomy MG was compared between the two groups, and the risk factors for postthymectomy MG were assessed. RESULTS: Of the 196 previously nonmyasthenic patients who underwent thymoma resection, 21 were GC-positive, whereas 175 were GC-negative. Postthymectomy MG developed in 11 (5.6%) patients and showed a higher incidence in the GC-positive group than in the GC-negative group (33.3% vs. 2.3%, p < 0.001). No postoperative radiotherapy and the presence of GCs were risk factors for postthymectomy MG in the univariate analysis. In multivariate analysis, invasive thymoma (hazard ratio [HR] = 9.835, 95% confidence interval [CI] = 1.358-105.372), postoperative radiotherapy (HR = 0.160, 95% CI = 0.029-0.893), and presence of GCs (HR = 15.834, 95% CI = 3.742-67.000) were significantly associated with postthymectomy MG. CONCLUSIONS: Thymic GCs may be a significant risk factor for postthymectomy MG. Even in patients with thymoma who do not show clinical symptoms of MG, postthymectomy MG should be considered, especially if thymic GCs are observed.

A Study on Superior Mesoporous Activated Carbons for Ultra Power Density Supercapacitor from Biomass Precursors.

A kenaf-derived activated carbon (KAC) for a high-power density supercapacitor was developed in this study through phosphoric acid activation. The N2/77K isothermal adsorption-desorption curve was used to estimate the textural properties of KAC based on BET and BJH and the pore size distribution based on NLDFT. The electrochemical properties of KAC were analyzed by using the coin-type cell applying 1 M SPBBF4/PC electrolyte, and the specific surface area and total pore volume were 1490-1942 m2/g and 1.18-3.18 cm3/g, respectively. The pore characteristics of KAC varied according to the activation temperature, and most KAC showed a mesoporous structure. As the activation temperature increased, the mesopore volume increased up to 700 °C, then decreased. The mesoporous structure of KAC resulted in a substantial decrease in the Warburg impedance as the ion diffusion resistance decreased. Hence, the specific capacitance of KAC decreased from 82.9 F/g to 59.48 F/g as the charge-discharge rate increased from 1 mA/g to 10 mA/g, with the rate of reduction at approximately 30%. The rate of reduction of KAC's specific capacitance was 50% lower compared with commercial activated carbon; hence, KAC is a more suitable electrode-active material for high power density supercapacitors.

Null variants in DYSF result in earlier symptom onset.

We investigated the clinical, laboratory, and genetic spectra in Korean patients with dysferlinopathy to clarify its genotype-phenotype correlation. We retrospectively reviewed 101 patients from 96 unrelated families with pathogenic variants of DYSF. The most common initial phenotype was Miyoshi myopathy in 50 patients. Median ages at examination and symptom onset were 23 [interquartile range (IQR): 18-30] and 36 years [IQR: 27-48], respectively. We observed 38 variants, including nine novel variants. Four variants (c.2494C > T, c.1284 + 2 T > C, c.663 + 1G > C, and c.2997G > T) in DYSF accounted for 62% of total allele frequencies of pathogenic variants. To analyze the genotype-phenotype correlation, we compared the clinical phenotype between patients with null/null (N/N; n = 55) and null/missense variants (N/M; n = 35). The N/N group had an earlier symptom onset age (median: 20 years [IQR: 17-25]) than the N/M group (median: 29 years [IQR: 23-35], p < .001). Total manual muscle testing scores in lower extremities were lower in the N/N group (median: 80 [IQR: 56-92]) than in the N/M group (median: 89 [IQR: 78-98], p = .013). Our study is the first to report that null variants in DYSF result in an earlier symptom onset than missense variants.

Patch-Type Vibration Visualization (PVV) Sensor System Based on Triboelectric Effect.

Self-powered wireless sensor systems have emerged as an important topic for condition monitoring in nuclear power plants. However, commercial wireless sensor systems still cannot be fully self-sustainable due to the high power consumption caused by excessive signal processing in a mini-electronic computing system. In this sense, it is essential not only to integrate the sensor system with energy-harvesting devices but also to develop simple data processing methods for low power schemes. In this paper, we report a patch-type vibration visualization (PVV) sensor system based on the triboelectric effect and a visualization technique for self-sustainable operation. The PVV sensor system composed of a polyethylene terephthalate (PET)/Al/LCD screen directly converts the triboelectric signal into an informative black pattern on the LCD screen without excessive signal processing, enabling extremely low power operation. In addition, a proposed image processing method reconverts the black patterns to frequency and acceleration values through a remote-control camera. With these simple signal-to-pattern conversion and pattern-to-data reconversion techniques, a vibration visualization sensor network has successfully been demonstrated.

Prevalence, Mortality, and Cause of Death in Charcot-Marie-Tooth Disease in Korea: A Nationwide, Population-Based Study.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous disorders that primarily affect the peripheral nervous system. Epidemiological studies of CMT have not yet been performed in Korea. OBJECTIVES: This study was performed to estimate the prevalence of CMT in Korea and the socioeconomic status, mortality, and causes of death of Korean patients with CMT. METHODS: Data on patients with CMT were obtained from the rare intractable disease registry and the National Health Insurance Service for the years 2005-2018. RESULTS: During the study period, 2,885 CMT patients were enrolled. The prevalence per 100,000 persons in 2018 was 5.2 (6.1 for men and 4.4 for women), peaking at ages 15-39 years, with almost twice as many men (n = 714) as women (n = 402) in this age group. Of the CMT patients, 226 (7.8%) were receiving medical aid, a public assistance program targeting poor individuals, at the time of diagnosis and 253 (8.8%) at last follow-up or death. From 2005 to 2017, 170 patients died, including 118 men and 52 women. The standardized mortality ratio (SMR) was 1.57 (95% CI 1.34-1.83) for all patients and did not differ in men and women. Age-specific SMR was highest in patients aged under 9 years, gradually declining thereafter. Neurologic disease as a cause of death was significantly more frequent in CMT patients than in the general population. CONCLUSIONS: This was the first nationwide epidemiologic study of CMT patients in Korea. This study confirmed the characteristics associated with the prevalence of and mortality from CMT by age and is the first to report the socioeconomic status and causes of death of CMT patients.

Prevalence and Socioeconomic Status of Patients with Genetic Myopathy in Korea: A Nationwide, Population-Based Study.

BACKGROUND: Genetic myopathy is a clinically and genetically heterogeneous group of genetic disorders characterized by progressive degeneration of skeletal muscles. Epidemiological studies of genetic myopathy have not yet been performed in Korea. OBJECTIVES: This study used data from the national health insurance claims database to determine the prevalence and socioeconomic status of patients with genetic myopathy in Korea. METHODS: We analyzed the Health Insurance Review and Assessment database from 2007 to 2011. Patients with genetic myopathy were defined based on diagnostic and procedure codes. We then evaluated the prevalence, types of health insurances, and medical expenses of these patients. RESULTS: During the 11-year study period, 2,988 patients with genetic myopathy were enrolled. Among them, 1,762 were men and 1,226 were women. The prevalence per 100,000 population in 2017 was 3.09 (3.94 for men and 2.24 for women). The prevalence of genetic myopathy among men <35 years old (8.33 per 100,000 population) was approximately twice that among women <35 years old (4.06 per 100,000 population). However, there was no significant difference in the prevalence of genetic myopathy among those ≥35 years old according to sex. The ratio of patients using medical aid among all genetic myopathy patients was approximately 4 times than that among the general population in Korea. The medical expenses per person for genetic myopathy increased from USD 2,027 in 2007 to USD 4,810 in 2017. CONCLUSIONS: Our study was the first nationwide epidemiologic study of the prevalence and socioeconomic status of patients with genetic myopathy in Korea. Our results confirmed a sex divergence in a younger population and those with low socioeconomic status among patients with genetic myopathy.

MiR-200c downregulates HIF-1α and inhibits migration of lung cancer cells.

BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor with a pivotal role in physiological and pathological responses to hypoxia. While HIF-1α is known to be involved in hypoxia-induced upregulation of microRNA (miRNA) expression, HIF-1α is also targeted by miRNAs. In this study, miRNAs targeting HIF-1α were identified and their effects on its expression and downstream target genes under hypoxic conditions were investigated. Cell migration under the same conditions was also assessed. METHODS: microRNAs that target HIF-1α were screened using 3'-untranslated region luciferase (3'-UTR-luciferase) reporter assays. The expression levels of HIF-1α and its downstream target genes after transfection with miRNA were assessed using quantitative RT-PCR and western blot analyses. The effect of the miRNAs on the transcriptional activity of HIF-1α was determined using hypoxia-responsive element luciferase (HRE-luciferase) assays. Cell migration under hypoxia was examined using the wound-healing assay. RESULTS: Several of the 19 screened miRNAs considerably decreased the luciferase activity. Transfection with miR-200c had substantial impact on the expression level and transcription activity of HIF-1α. The mRNA level of HIF-1α downstream genes decreased in response to miR-200c overexpression. MiR-200c inhibited cell migration in normoxia and, to a greater extent, in hypoxia. These effects were partly reversed by HIF-1α expression under hypoxic conditions. CONCLUSION: miR-200c negatively affects hypoxia-induced responses by downregulating HIF-1α, a key regulator of hypoxia. Therefore, overexpression of miR-200c might have therapeutic potential as an anticancer agent that inhibits tumor hypoxia.

Risk factors for osteoporosis in chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients possess multiple risk factors for osteoporosis, but few studies have evaluated bone mineral density (BMD) in CIDP patients. METHODS: We retrospectively compared the BMD of CIDP patients with that of normal controls, and evaluated the clinical factors associated with osteoporosis. RESULTS: Total BMD was lower in CIDP patients than in normal controls (P = 0.017). In a comparison of 16 osteoporotic CIDP patients with 25 non-osteoporotic patients, the cumulative prednisolone dose was lower (P = 0.022) and the duration from disease onset to BMD measurement was shorter (P = 0.014) in osteoporotic patients than in non-osteoporotic patients. Function, as measured by modified Rankin scale score within 3 years of the BMD measurement, was worse in osteoporotic than in non-osteoporotic patients (P = 0.008). DISCUSSION: BMD in CIDP patients was significantly lower than in normal controls. Functional status rather than cumulative steroid dose was associated with osteoporosis. Muscle Nerve 58: 407-412, 2018.

ADSSL1 mutation relevant to autosomal recessive adolescent onset distal myopathy.

OBJECTIVE: Distal myopathy is a heterogeneous group of muscle diseases characterized by predominant distal muscle weakness. A study was done to identify the underlying cause of autosomal recessive adolescent onset distal myopathy. METHODS: Four patients from 2 unrelated Korean families were evaluated. To isolate the genetic cause, exome sequencing was performed. In vitro and in vivo assays using myoblast cells and zebrafish models were performed to examine the ADSSL1 mutation causing myopathy pathogenesis. RESULTS: Patients had an adolescent onset distal myopathy phenotype that included distal dominant weakness, facial muscle weakness, rimmed vacuoles, and mild elevation of serum creatine kinase. Exome sequencing identified completely cosegregating compound heterozygous mutations (p.D304N and p.I350fs) in ADSSL1, which encodes a muscle-specific adenylosuccinate synthase in both families. None of the controls had both mutations, and the mutation sites were located in well-conserved regions. Both the D304N and I350fs mutations in ADSSL1 led to decreased enzymatic activity. The knockdown of the Adssl1 gene significantly inhibited the proliferation of mouse myoblast cells, and the addition of human wild-type ADSSL1 reversed the reduced viability. In an adssl1 knockdown zebrafish model, muscle fibers were severely disrupted, which was evaluated by myosin expression and birefringence. In these conditions, supplementing wild-type ADSSL1 protein reversed the muscle defect. INTERPRETATION: We suggest that mutations in ADSSL1 are the novel genetic cause of the autosomal recessive adolescent onset distal myopathy. This study broadens the genetic and clinical spectrum of distal myopathy and will be useful for exact molecular diagnostics.

Pulmonary persistence of graphene nanoplatelets may disturb physiological and immunological homeostasis.

Accumulated evidence suggests that chronic pulmonary accumulation of harmful particles cause adverse pulmonary and systemic health effects. In our previous study, most of the graphene nanoplatelet (GNP) remained in the lung until 28 days after a single instillation. In this study, we sought to evaluate the local and systemic health effect after a long pulmonary persistence of GNP. As expected, GNP remained in the lung on day 90 after a single intratracheal instillation (1.25, 2.5 and 5 mg kg-1 ). In the lung exposed at the highest dose, the total number of cells and the percentage of lymphocytes significantly increased in the BAL fluid with an increase in both the number of GNP-engulfed macrophages and the percentage of apoptotic cells. A Th1-shifted immune response, the elevated chemokine secretion and the enhanced expression of cytoskeletal-related genes were observed. Additionally, the expression of natriuretic-related genes was noteworthy altered in the lungs. Moreover, the number of white blood cells (WBC) and the percentage of macrophages and neutrophils clearly increased in the blood of mice exposed to a 5-mg kg-1 dose, whereas total protein, BUN and potassium levels significantly decreased. In conclusion, we suggest that the long persistence of GNP in the lung may cause adverse health effects by disturbing immunological- and physiological-homeostasis of our body. Copyright © 2016 John Wiley & Sons, Ltd.

Spinal cord involvement in Behçet's disease.

BACKGROUND: Spinal cord involvement in Behçet's disease is not well studied. OBJECTIVE: To evaluate the clinical, laboratory and magnetic resonance imaging characteristics of spinal cord involvement in Behçet's disease. METHODS: We retrospectively reviewed 10 spinal cord involvements in seven patients with Behçet's disease. RESULTS: The median age of onset for spinal cord involvement was 32 (23-45 years). Two patients showed a secondary progressive course. Cerebrospinal fluid findings revealed mild to moderate pleocytosis and/or elevated protein levels. In eight spinal cord involvements, the lesion was longer than three vertebrae. Serum anti-aquaporin-4 antibody was negative in all four patients tested. CONCLUSIONS: Longitudinally extensive transverse myelitis is a characteristic manifestation of spinal cord involvement in Behçet's disease.

MicroRNA library screening identifies growth-suppressive microRNAs that regulate genes involved in cell cycle progression and apoptosis.

Micro(mi)RNAs play important and varied roles in tumorigenesis; however, the full repertoire of miRNAs that affect cancer cell growth is not known. In this study, an miRNA library was screened to identify those that affect the growth of A549 tumor cells. Among 300 miRNAs, miR-28-5p, -323-5p, -510-5p, -552-3p, and -608 were the most effective in inhibiting cell growth. More specifically, overexpressing miR-28-5p, -323-5p, and -510-5p induced G1 arrest, as determined by flow cytometry, whereas that of miR-608 induced cell death in a caspase-dependent manner. Moreover, several genes involved in apoptosis and cell cycle progression were downregulated upon overexpression of each of the five miRNAs, with the functional targets of miR-552-3p and miR-608 confirmed by microarray, quantitative real-time PCR, and luciferase reporter assay. In miR-608-transfected cells, B cell lymphoma 2-like 1 (BCL2L1), D-type cyclin 1 (CCND1), CCND3, cytochrome b5 reductase 3 (CYB5R3), phosphoinositide 3-kinase regulatory subunit 2 (PIK3R2), specificity protein 1 (SP1), and phosphorylated Akt were all downregulated, while Bcl-2-interacting killer (BIK) was upregulated. Moreover, miR-608 was determined to have a suppressive function on tumor growth in an NCI-H460 xenograft model. These findings provide insights into the roles of five miRNAs in growth inhibition and their potential function as cancer therapeutics.

Predictive factors for myasthenic crisis after videoscopic thymectomy in patients with myasthenia gravis.

INTRODUCTION: Predictive factors for myasthenic crisis after transsternal thymectomy have been reported, but little is known about myasthenic crisis after videoscopic thymectomy (MCAVT). METHODS: We investigated 146 myasthenia gravis patients who underwent videoscopic thymectomy. RESULTS: Patients with MCAVT had a lower forced vital capacity (FVC) (2.1 vs. 3.0 L, P < 0.001) than those without. Low-frequency repetitive nerve stimulation showed decremental responses of the orbicularis oculi (47.1% vs. 18.1%, P = 0.001) and nasalis muscles (54.1% vs. 21.4%, P < 0.001), which were more pronounced in patients with MCAVT than those without. According to multivariate analysis, FVC (OR 0.144, 95% confidence interval [CI], 0.044-0.479, P = 0.002) and decremental response of orbicularis oculi (odds ratio, 1.029; 95% CI, 1.001-1.058, P = 0.044) were independently associated with MCAVT. CONCLUSIONS: FVC and decremental response of orbicularis oculi were associated with MCAVT.

Effect of enzyme replacement therapy in late onset Pompe disease: open pilot study of 48 weeks follow-up.

Late-onset Pompe disease (LOPD) is an autosomal recessive disorder caused by deficiency of the enzyme acid glucosidase alfa (GAA). Recently, enzyme replacement therapy (ERT) using recombinant human GAA (rhGAA) became clinically available, and is expected to modify the clinical course in LOPD of various stages. In this study, we evaluated the efficacy and adverse events of ERT for 48 weeks in Korean LOPD patients. Five Korean LOPD patients were included in the study. At baseline, clinical and laboratory features, including muscular and pulmonary function, were assessed, and rhGAA was infused every 2 weeks. Then, patients were examined at every 12-week interval for evaluation of changes in motor and pulmonary function for 48 weeks along with adverse reactions to ERT. The muscular and pulmonary function of the patients varied depending on the baseline condition of the patient after 48 weeks of ERT. However, the overall function of the patients showed stabilization of the disease rather than the improvement seen in infantile-onset Pompe disease. This is the first clinical study on ERT of Korean LOPD patients. Results of our study showed stabilization of muscular and pulmonary function in LOPD patients for 48 weeks with a favorable prognosis for patients who received early diagnosis and ambulatory patients. One of our patients developed a serious anaphylactic reaction, which necessitated the cessation of further ERT. Therefore, our study shows that early diagnosis and ERT are important in preventing further deterioration of the disease.

The significance of clinical and laboratory features in the diagnosis of glycogen storage disease type v: a case report.

Glycogen storage disease type V (GSD-V) is the most common disorder of muscle glycogenosis with characteristic clinical and laboratory findings. A 32-yr-old woman complained of exercise intolerance and myoglobulinuria since early adolescence. She reported several episodes of second-wind phenomenon. Physical examination did not show any neurological abnormality, including fixed muscle weakness or atrophy. Serum creatine kinase level was 1,161 IU/L at rest. The result of the non-ischemic forearm exercise test was compatible with GSD-V. Mutation analysis identified the compound heterozygous mutations of the PYGM, p.D510fs and p.F710del, which has not yet been reported in Korea. The present case recognizes that detail clinical and laboratory analysis is the first step in the diagnosis of GSD-V.

Clinical Application of Optical Genome Mapping for Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1. Methods: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer's dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM. Results: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM. In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM. Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis. Conclusions: OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.

Transcriptome profiling of skeletal muscles from Korean patients with Bethlem myopathy.

Bethlem myopathy is one of the collagens VI-related muscular dystrophies caused by mutations in the collagen VI genes. The study was designed to analyze the gene expression profiles in the skeletal muscle of patients with Bethlem myopathy. Six skeletal muscle samples from 3 patients with Bethlem myopathy and 3 control subjects were analyzed by RNA-sequencing. 187 transcripts were significantly differentially expressed, with 157 upregulated and 30 downregulated transcripts in the Bethlem group. Particularly, 1 (microRNA-133b) was considerably upregulated, and 4 long intergenic non-protein coding RNAs, LINC01854, MBNL1-AS1, LINC02609, and LOC728975, were significantly downregulated. We categorized differentially expressed gene using Gene Ontology and showed that Bethlem myopathy is strongly associated with the organization of extracellular matrix (ECM). Kyoto Encyclopedia of Genes and Genomes pathway enrichment reflected themes with significant enrichment of the ECM-receptor interaction (hsa04512), complement and coagulation cascades (hsa04610), and focal adhesion (hsa04510). We confirmed that Bethlem myopathy is strongly associated with the organization of ECM and the wound healing process. Our results demonstrate transcriptome profiling of Bethlem myopathy, and provide new insights into the path mechanism of Bethlem myopathy associated with non-protein coding RNAs.

Anti-titin antibodies are associated with myocarditis in patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) can affect cardiac muscles with variable presentations. Myocarditis is a rare but potentially serious cardiac manifestation of MG. Although thymomas and anti-titin antibodies have been suggested as risk factors for myocarditis in patients with MG, their independent influence on myocarditis has rarely been assessed. METHODS: A retrospective chart review was conducted on 247 patients diagnosed with MG who were tested for anti-titin antibodies. Myocarditis was diagnosed on the basis of the European Society of Cardiology 2013 Task Force criteria for clinically suspected myocarditis. Patients were classified into myocarditis-positive and myocarditis-negative groups. Multivariate analysis was performed to analyze the risk factors for myocarditis. RESULTS: Of the 247 patients, 25 (10.1%) were myocarditis-positive and 222 (89.9%) were myocarditis-negative. Anti-titin antibody positivity was higher in the myocarditis-positive group than in the myocarditis-negative group (68.0% vs. 28.4%, p < 0.001). A history of MG crisis was more frequent in the myocarditis-positive group than in the myocarditis-negative group (64.0% vs. 10.4%, p < 0.001). The presence of anti-titin antibodies (odds ratio [OR] 7.906; confidence interval [CI] 2.460-25.401) and MG crisis (OR 24.807; CI 7.476-82.311) was significantly associated with myocarditis. The Cox regression model showed that the anti-titin antibody levels (hazard ratio [HR] 3.639; 95% CI 1.557-8.505) and MG crisis (HR 6.137; 95% CI 2.639-14.272) were significant risk factors for the development of myocarditis. CONCLUSION: The presence of anti-titin antibody was associated with myocarditis in patients with MG, whereas thymoma was not. Although rare, early suspicion of myocarditis could be required, especially in patients with MG having anti-titin antibodies.

Clinical significance of anti-NT5c1A autoantibody in Korean patients with inflammatory myopathies.

To explore the clinical significance of anti-cytosolic 5'-nucleoditase 1A (NT5c1A) antibody seropositivity in inflammatory myopathies, we measured anti-NT5c1A antibodies and analyzed their clinical features. Anti-NT5c1A antibodies were measured in the sera of 103 patients with inflammatory myopathies using an enzyme-linked immunosorbent assay. Positivity for anti-NT5c1A antibody was found in 13 (12.6%) of 103 patients with inflammatory myopathy. Anti-NT5c1A antibody was most frequently identified in patients with inclusion body myositis (IBM) (8/20, 40%), followed by dermatomyositis (2/13, 15.4%), immune-mediated necrotizing myopathy (2/28, 7.1%), and polymyositis (1/42, 2.4%). In eight patients with the anti-NT5c1A antibody-seropositive IBM, the median age at symptom onset was 54 years (interquartile range [IQR]: 48-57 years), and the median disease duration was 34 months (IQR: 24-50 months]. Knee extension weakness was greater than or equal to hip flexion weakness in eight (100%) patients, and finger flexion strength was less than shoulder abduction in three (38%) patients. Dysphagia symptoms were found in three (38%) patients. The median serum CK level was 581 IU/l (IQR: 434-868 IU/L]. Clinically significant differences were not found between anti-NT5c1A antibody-seropositive and seronegative IBM groups with respect to gender, age at symptom onset, age at diagnosis, disease duration, serum CK values, presence of other autoantibodies, dysphagia, and the pattern of muscle impairment. Although anti-NT5c1A antibody is known to be associated with IBM, seropositivity has also been noted in non-IBM inflammatory myopathies, and is insufficient to have clinical significance by itself. These findings have important implications for interpreting anti-NT5c1A antibody test results as the first study in Korea.

Transcriptome analysis of skeletal muscle in dermatomyositis, polymyositis, and dysferlinopathy, using a bioinformatics approach.

Background: Polymyositis (PM) and dermatomyositis (DM) are two distinct subgroups of idiopathic inflammatory myopathies. Dysferlinopathy, caused by a dysferlin gene mutation, usually presents in late adolescence with muscle weakness, degenerative muscle changes are often accompanied by inflammatory infiltrates, often resulting in a misdiagnosis as polymyositis. Objective: To identify differential biological pathways and hub genes related to polymyositis, dermatomyositis and dysferlinopathy using bioinformatics analysis for understanding the pathomechanisms and providing guidance for therapy development. Methods: We analyzed intramuscular ribonucleic acid (RNA) sequencing data from seven dermatomyositis, eight polymyositis, eight dysferlinopathy and five control subjects. Differentially expressed genes (DEGs) were identified by using DESeq2. Enrichment analyses were performed to understand the functions and enriched pathways of DEGs. A protein-protein interaction (PPI) network was constructed, and clarified the gene cluster using the molecular complex detection tool (MCODE) analysis to identify hub genes. Results: A total of 1,048, 179 and 3,807 DEGs were detected in DM, PM and dysferlinopathy, respectively. Enrichment analyses revealed that upregulated DEGs were involved in type 1 interferon (IFN1) signaling pathway in DM, antigen processing and presentation of peptide antigen in PM, and cellular response to stimuli in dysferlinopathy. The PPI network and MCODE cluster identified 23 genes related to type 1 interferon signaling pathway in DM, 4 genes (PDIA3, HLA-C, B2M, and TAP1) related to MHC class 1 formation and quality control in PM, and 7 genes (HSPA9, RPTOR, MTOR, LAMTOR1, LAMTOR5, ATP6V0D1, and ATP6V0B) related to cellular response to stress in dysferliniopathy. Conclusion: Overexpression of genes related to the IFN1 signaling pathway and major histocompatibility complex (MHC) class I formation was identified in DM and PM, respectively. In dysferlinopathy, overexpression of HSPA9 and the mTORC1 signaling pathway genes was detected.