Polymyositis Publications (10950)


Polymyositis Publications

Inclusion body myositis (IBM) is characterised by a combination of inflammatory and degenerative changes affecting muscle. While the primary cause of IBM is unknown, genetic factors may influence disease susceptibility. We conducted the largest genetic association study to date in IBM, investigating immune-related genes using the Immunochip. Read More

252 Caucasian IBM cases were recruited from 11 countries through the Myositis Genetics Consortium (MYOGEN), and compared with 1,008 ethnically matched controls. Classical HLA alleles and amino acids were imputed using SNP2HLA.
HLA was confirmed as the most strongly associated region (p=3.58x10(-33) ) in IBM. HLA imputation identified three independent associations with HLA-DRB1*03:01, -DRB1*01:01, and -DRB1*13:01, although the strongest association was with amino acid positions 26 and 11 of the HLA-DRB1 molecule. No association with anti-cN-1A positive status was found independent of HLA-DRB1*03:01. There was no association of HLA genotypes with age of onset of IBM. Three non-HLA regions reached suggestive significance, including chr3(p21.21), an established risk locus for autoimmune disease, where a frameshift mutation in CCR5 is thought to be the causal variant.
This is the largest most comprehensive genetic association study to date in IBM. The data confirm that HLA is the most strongly associated region and identifies novel amino acid associations that may explain the risk in this locus; these amino acid associations differentiate IBM from polymyositis and dermatomyositis, and may determine properties of the peptide-binding groove allowing it to preferentially bind auto-antigenic peptides. A novel suggestive association within the chr3(p21.21) locus suggests a role for CCR5. This article is protected by copyright. All rights reserved.

Intern Med J
Intern Med J 2017 Jan;47(1):112-115
Rheumatology Department, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

In South Australia, between 2000 and 2014, 57 patients with idiopathic inflammatory myositis (IIM) were treated with intravenous immunoglobulin (IVIg). We reviewed disease characteristics to determine predictors of response to therapy and IVIg dosing and duration to identify opportunities to rationalise IVIg use. Patients with dermatomyositis/polymyositis had a response rate of 77% and were more likely than inclusion body myositis to respond to therapy. Read More

Consideration should be given to the use of the lowest possible dose of IVIg and to the undertaking of trials of cessation of IVIg in patients with stable IIM.

Am J Case Rep
Am J Case Rep 2017 Jan 5;18:17-21. Epub 2017 Jan 5.
MRC Centre for Neuromuscular Diseases and Division of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, United Kingdom.

BACKGROUND Miyoshi myopathy (MM) is an autosomal-recessive muscle disorder caused by mutations in the DYSF gene. Clinical features and histopathological changes in dysferlinopathies may mimic inflammatory myopathies and a high degree of clinical suspicion is required to guide the genetic investigation. CASE REPORT We report the case of a 16-year-old male who presented with severe bilateral calf pain and elevated CK levels (15 000 IU/l) who was on prolonged steroid therapy prompted by the clinical suspicion of inflammatory myopathy. Read More

Three years into his illness, he was referred for neuromuscular evaluation presenting with untreatable muscle pain and progressive weakness. The diagnosis of "refractory polymyositis" was revisited. Targeted exome sequencing revealed homozygous pathogenic mutations in the DYSF gene, confirming a diagnosis of Miyoshi myopathy. CONCLUSIONS Our case illustrates that severe muscle pain may be the initial feature of Miyoshi myopathy and should be considered in the differential diagnosis of inflammatory myopathies. Although the described patient reported partial clinical improvement in muscle pain, steroid treatment is not an effective therapy for dysferlinopathy patients and it did not prevent disease progression. In addition, we confirm the utility of next-generation sequencing approaches to myopathies, particularly in complex or unusual cases when muscle biopsy is not available.

Clin. Exp. Med.
Clin Exp Med 2016 Dec 30. Epub 2016 Dec 30.
Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang, 110001, People's Republic of China.

DNase1l3 is an endonuclease to degrade the chromatin of apoptotic or necrotic cells. Serum DNase1l3 may fulfill the function of clearance of chromatin released into the circulation by dying cells, which can trigger autoimmune responses. To date, it remains unclear whether serum DNase1l3 level associates with the pathogenesis of autoimmune diseases. Read More

Sixty-eight patients with dermatomyositis/polymyositis (DM/PM, n = 30), systemic lupus erythematosus (SLE, n = 20) and rheumatoid arthritis (RA, n = 18), as well as 26 healthy blood donors were enrolled in the present study. Serum levels of DNase1l3 were quantified by enzyme-linked immunosorbent assay. DNASE1L3 activity in serum was estimated by the capability of serum to digest nucleosomal DNA. Clinical, biochemical, serological and other markers of disease activity (CRP, ESR, C3, C4, anti-Jo-1 and anti-dsDNA, etc.) were measured by standard laboratory procedure. We found a decrease in DNase1l3 level in the DM/PM and SLE patients, resulting in the reduction in serum activity to digest nucleosome DNA. In contrast, the level and activity of DNase1l3 remained unchanged in the RA patients. The DNase1l3 level was relatively lower in the DM/PM patients with anti-Jo-1 antibody and interstitial lung disease, and in the SLE patients with SLE disease activity index higher than 6, renal involvement and anti-dsDNA antibody. DNase1l3 level negatively correlated with CRP and IgG in the PM/DM patients and correlated with ESR in the SLE patients. We found a significant reduction in serum DNase1l3 level in DM/PM and SLE, which may associate with clinic features and disease activity.

Neurology 2016 Dec 30. Epub 2016 Dec 30.
From the Department of Genome Medicine Development (A.U., A.N., K.H., I.N.), Medical Genome Center, and Department of Neuromuscular Research (A.U., A.N., R.S.T., K.H., I.N.), National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo; Department of Education (A.N.), Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi; Department of Pediatric Neurology (R.S.T.), National Hospital Organization, Utano National Hospital; Department of Neurology (K.H.), Graduate School of Medicine, Kyoto University; Department of Allergy and Rheumatology (M.K.), Nippon Medical School Graduate School of Medicine; and Division of Rheumatology (M.K.), Department of Internal Medicine, and Department of Neurology (Y.W., S.S., N.S.), Keio University School of Medicine, Tokyo, Japan.

To evaluate the diagnostic value of myxovirus resistance A (MxA) expression in the cytoplasm of myofibers in the diagnosis of dermatomyositis (DM).
We assessed the sensitivity and specificity of the sarcoplasmic expression of MxA in muscles with DM by immunohistochemistry in consecutive cases of DM (n = 34) and other idiopathic inflammatory myopathies (n = 120: 8 with polymyositis, 16 with anti-tRNA-synthetase antibody-associated myositis, 46 with immune-mediated necrotizing myopathy, and 50 with inclusion body myositis) and compared them with conventional pathologic hallmarks of DM, including perifascicular atrophy (PFA) and membrane attack complex (MAC) deposition on endomysial capillaries.
The sensitivity and specificity of sarcoplasmic MxA expression were 71% and 98%, respectively. Read More

While the specificity was almost comparable to that of PFA and capillary MAC deposition, the sensitivity was higher, with PFA showing 47% sensitivity and 98% specificity and capillary MAC deposition showing 35% sensitivity and 93% specificity. Of note, in patients with DM with typical skin rash but no PFA, 44% of the samples showed sarcoplasmic MxA expression, which was higher than the 17% sensitivity of capillary MAC deposition in the population.
Sarcoplasmic MxA expression detected by immunohistochemistry is a more sensitive marker of DM than the conventional hallmarks, indicating its practical utility in the diagnosis of DM. It may well be included in the routine immunohistochemistry panel for myositis.
This study provides Class II evidence that immunohistochemistry-detected sarcoplasmic MxA expression accurately identifies patients with dermatomyositis.

Biomol Ther (Seoul)
Biomol Ther (Seoul) 2017 Jan;25(1):80-90
Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, S1P₁₋₅. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Read More

Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn's disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications.

J. Autoimmun.
J Autoimmun 2016 Dec 22. Epub 2016 Dec 22.
Department of Medicine, Unit of Rheumatology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. Electronic address:

The type I interferon (IFN) system has recently been suggested to play important and essential roles in the pathogenesis of myositis. However, a clarification of how type I IFNs could function as triggering factor(s) in the pathogenesis of myositis has yet failed. Through activation of the type I IFN system, the host defense peptide LL-37 carries numerous immunomodulatory properties and is implicated in the pathogenesis of several other autoimmune diseases, including systemic lupus erythematosus (SLE). Read More

The expression of LL-37 can be regulated by various endogenous factors including the active form of vitamin D (25(OH)D3). The aim of this study was to explore a potential role of LL-37 in relation to the type I IFN system in patients with polymyositis (PM) and dermatomyositis (DM) and to compare these with SLE patients and healthy controls. We investigated muscle (3 PM, 5 DM) and symptomatic (5 DM) and non-symptomatic (3 PM, 3 DM) skin biopsies from patients with short disease duration and muscle biopsies (3 PM, 1 DM) from patients with long disease duration. Six SLE patients with symptomatic and non-symptomatic skin and five muscle and six skin biopsies from healthy individuals served as controls. Tissue specimens were immunohistochemically stained for LL-37, neutrophils (CD66b), plasmacytoid dendritic cells (BDCA-2), myxovirus resistance protein A (MxA), and macrophages (CD68, CD163). In addition, LL-37 and CD66b double staining was also performed. Serum levels of 25(OH)D3 were investigated in PM and DM patients with short disease duration (3 PM, 5 DM) and in 40 healthy controls. We found that the expression of LL-37, BDCA-2 (the major producer of type I IFNs), MxA (an interferon-inducible protein), and macrophages were higher in muscle tissue of PM and DM patients compared to healthy controls. The LL-37 expression was mainly derived from neutrophils. Neutrophils were increased in both symptomatic and non-symptomatic skin of myositis and SLE patients and BDCA-2 was increased in symptomatic DM skin when compared to healthy controls. Moreover, the expression of MxA in symptomatic and non-symptomatic skin of SLE patients was higher when compared to both myositis patients and healthy controls. There was no difference in the expression of LL-37 in skin of myositis and SLE patients compared to healthy controls. All PM and DM patients with a short disease duration had low 25(OH)D3 levels compared to healthy controls. In conclusion, the present study supports our hypothesis that LL-37 may activate type I IFNs, which could initiate and perpetuate an inflammatory process. The prolonged exposure of the immune system to type I IFNs may eventually break tolerance and lead to autoimmune myositis.

Respir Investig
Respir Investig 2017 Jan 30;55(1):24-32. Epub 2016 Sep 30.
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi 77, Kurume, Fukuoka 830-0011, Japan. Electronic address:

We attempted to clarify whether the presence of anti-aminoacyl-transfer RNA synthetase antibody (anti-ARS Ab) or anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is associated with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD).
We retrospectively investigated 22 patients with PM/DM-ILD (10 positive for anti-ARS Ab and nine positive for anti-MDA5 Ab) for whom antibody analysis of conserved serum was possible. We assessed mortality in the first three months as the therapeutic response in the acute phase and compared changes in clinical data for up to one year considered as the chronic phase. Read More

We classified the clinical changes over the year into three groups: Improvement (increased % vital capacity [%VC] or diffusing capacity of the lung for carbon monoxide [%DLCO]≥10 or 15%), deterioration (decreased %VC or %DLCO≥10 or 15%), and no change (remainder of the changes). The extent of abnormality demonstrated by high-resolution computed tomography (HRCT) was scored.
Positivity for anti-MDA5 Ab, but not for anti-ARS Ab, was associated with mortality in the first 3 months. Evaluation of the therapeutic response in the first year showed that positivity for the anti-ARS Ab, but not for the anti-MDA5 Ab, was associated with an improvement in %DLCO and a decline in the serum KL-6 levels. Positivity for the anti-ARS Ab or negativity for anti-MDA5 Ab was associated with a greater decrease in bronchial dilatation as seen by HRCT.
Anti-ARS and anti-MDA5 Abs are associated with the therapeutic response of PM/DM-ILD.

Clin. Exp. Rheumatol.
Clin Exp Rheumatol 2016 Nov-Dec;34(6):1098-1100. Epub 2016 Oct 27.
Department of Rheumatology, Department of Internal Medicine, Azienda Ospedaliera ASMN, IRCSS, Reggio Emilia, Italy.

Dermatomyositis (DM) and polymyositis (PM) commonly cause weakness of the thigh muscles. However, it is debated whether DM and PM affect similar thigh muscles. Muscle oedema on fat-suppressed MRI sequences is thought to represent active inflammation. Read More

In this study, we aimed to assess which thigh muscle groups are preferentially inflamed in DM and PM, respectively, using short-tau inversion-recovery MRI sequences.
We analysed 71 patients from 2 Rheumatology centres, 31 with DM and 40 with PM diagnosed according to the Bohan and Peter criteria. MRI oedema (1=present, 0=absent) was assessed bilaterally on fat-suppressed sequences in 17 pelvic floor and thigh muscles. An MRI oedema score (range 0-17) was calculated by adding the separate scores bilaterally and dividing them by two. Inter-rater variability was assessed by intraclass correlation coefficient. Fisher's exact test was used to compare binomial data.
Age and gender ratio were similar in patients with DM and PM. Disease duration (months, mean±SD) was shorter (20±31) in DM than in PM (53±69) (p=0.02). The intraclass correlation coefficient between the radiologists involved was 0.78. Muscle oedema was more common in DM than in PM except in the posterior thigh muscles. In particular, 68% of patients with DM had involvement of at least one anterior thigh muscle versus 38% of patients with PM (p=0.02).
Compared with PM, DM affects more thigh muscles, except those of the posterior compartment, which are equally involved in both disorders. These findings may be useful to target physiotherapy at the more frequently affected muscles.