Idiopathic Inflammatory Myopathy Disease Research Articles

Fibroblast activation protein inhibitor positron emission tomography imaging in muscles of patients with idiopathic inflammatory myopathy.

Mesenchymal stromal cells in muscles participate in regeneration following muscle injury. This study explored the potential of [18F]fibroblast activation protein inhibitor (FAPI)-42 positron emission tomography (PET) targeting mesenchymal stromal cells to evaluate disease activity of idiopathic inflammatory myopathy (IIM). Patients with IIM (n = 26) were prospectively included and underwent [18F]FAPI-42 PET/CT and whole-body MRI between January 2023 and July 2023. Patients with malignancies were retrospectively included in the control group and only underwent [18F]FAPI-42 PET/CT (n = 28). [18F]FAPI-42 PET/CT images were evaluated using for avid-FAPI uptake and the target-to-background ratio (TBR). Whole-body MRI was evaluated for oedema, fatty infiltration, and atrophy in 42 muscles in the IIM group. The global FAPI- and MRI-derived parameters were calculated for each. . Clinical assessment of disease activity and muscle strength were collected. Patients with IIM had significantly higher global FAPI-avid muscle ratios (0.68 [interquartile range (IQR): 0.45, 0.79] vs 0.06 [IQR: 0, 0.11], p< 0.001) and global muscle TBR (2.26 [IQR: 1.71, 2.75] vs 1.23 [IQR: 1.02, 1.52], p< 0.001) compared with controls. In the IIM group, the median TBR was higher in muscles with oedema than in those without (2.44 [IQR: 1.46, 3.27] vs 1.31 [IQR: 0.95, 1.99], p< 0.001). Global FAPI-avid muscle ratios significantly correlated with global oedema score (r = 0.833), muscle strength (r=-0.649), serum creatine kinase (r = 0.456), and disease activity index (r = 0.495-0.621). Increased [18F]FAPI-42 uptake was associated with muscle oedema in IIM. FAPI-derived parameters correlated with IIM disease activity. [18F]FAPI-42 is a promising PET tracer for evaluating IIM disease activity.

Anti-synthetase syndrome is associated with a higher risk of hospitalization among patients with idiopathic inflammatory myopathy and COVID-19.

Data with fine granularity about COVID-19-related outcomes and risk factors were still limited in the idiopathic inflammatory myopathies (IIMs) population. This study aimed to investigate clinical factors associated with hospitalized and severe COVID-19 in patients with IIMs, particularly those gauged by myositis-specific antibodies. This retrospective cohort study was conducted in the Renji IIM cohort in Shanghai, China, under an upsurge of SARS-CoV-2 omicron variant infections from December 2022 to January 2023. Clinical data were collected and analyzed by multivariable logistic regression to determine risk factors. High-dimensional flow cytometry analysis was performed to outline the immunological features. Among 463 infected patients in the eligible cohort (n=613), 65 (14.0%) were hospitalized, 19 (4.1%) suffered severe COVID-19, and 10 (2.2%) died. Older age (OR=1.59/decade, 95% CI 1.18 to 2.16, p=0.003), requiring family oxygen supplement (2.62, 1.11 to 6.19, 0.028), patients with anti-synthetase syndrome (ASyS) (2.88, 1.12 to 7.34, 0.027, vs. other dermatomyositis), higher IIM disease activity, and prednisone intake >10mg/day (5.59, 2.70 to 11.57, <0.001) were associated with a higher risk of hospitalization. Conversely, 3-dose inactivated vaccination reduced the risk of hospitalization (0.10, 0.02 to 0.40, 0.001, vs. incomplete vaccination). Janus kinase inhibitor (JAKi) pre-exposure significantly reduced the risk of severe COVID-19 in hospitalized patients (0.16, 0.04 to 0.74, 0.019, vs. csDMARDs). ASyS patients with severe COVID-19 had significantly reduced peripheral CD4+ T cells, lower CD4/CD8 ratio, and fewer naive B cells but more class-switched memory B cells compared with controls. ASyS and family oxygen supplement were first identified as risk factors for COVID-19-related hospitalization in patients with IIMs. JAKi pre-exposure might protect IIM patients against severe COVID-19 complications.

The role of neutrophil extracellular traps and proinflammatory damage-associated molecular patterns in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are a group of systemic autoimmune diseases characterized by immune-mediated muscle injury. Abnormal neutrophil extracellular traps (NETs) can be used as a biomarker of IIM disease activity, but the mechanism of NET involvement in IIMs needs to be elucidated. Important components of NETs, including high-mobility group box 1, DNA, histones, extracellular matrix, serum amyloid A, and S100A8/A9, act as damage-associated molecular patterns (DAMPs) to promote inflammation in IIMs. NETs can act on different cells to release large amounts of cytokines and activate the inflammasome, which can subsequently aggravate the inflammatory response. Based on the idea that NETs may be proinflammatory DAMPs of IIMs, we describe the role of NETs, DAMPs, and their interaction in the pathogenesis of IIMs and discuss the possible targeted treatment strategies in IIMs.

An Unusual Presentation of Anti Pm/Scl Antibody-positive Idiopathic Inflammatory Myositis

ABSTRACT Idiopathic inflammatory myopathies are the heterogeneous group of diseases that affect multiple systems apart from the skeletal muscles, preferentially affecting the proximal skeletal muscle. We present a rare case with quadriparesis, purely involvement of proximal muscles without any extra muscular symptoms with positive Anti Pm/Scl antibodies. Our patients was 52 year old male who presented to be symptomatic with generalized swelling all over the body followed by progressive pure proximal group of muscles motor weakness of all four limbs without sensory involvement. He also developed oropharyngeal weakness, in the form of nasal regurgitation of food and significant weight loss. C reactive protein was 22 mg/L, erthryocyte sedimentation rate was 30 mm after 1 h, and liver enzymes were also increased (aminotransferase was 236 U/L and alanine aminotransferase was 145 U/L). His lactate dehydrogenase was 1175 U/L whereas creatinine kinase was 3290 U/L. His ANA profile was positive for Anti Pm/ Scl antibodies. MRI of both thighs was suggestive of diffuse inflammatory changes in both lower limbs and pelvic girdle and PET CT was suggestive of increased uptake in proximal limb muscles. He was managed with pulse Inj Methylprednisolone and intravenous Immunoglobulin. This followed by oral prednisolone for a few months than slow tapering. In Conclusion that Anti Pm/Scl antibody positive idiopathic inflammatory myositis can also present atypically without any other systemic manifestation and weakness in lower limb more than upper limbs. Idiopathic inflammatory myopathies disease is one of the treatable diseases that repones to immunomodulation therapy.

Defining the clinical utility of PET or PET-CT in idiopathic inflammatory myopathies: A systematic literature review

ObjectivesPositron emission tomography (PET), often combined with computed tomography (CT), is a well-established tool for diagnosing malignancy and inflammatory disease. The idiopathic inflammatory myopathies (IIM) are chronic, multi-system diseases characterised by skeletal muscle inflammation, the potential for extramuscular manifestations such as interstitial lung disease (ILD) and an increased risk of malignancy. We performed a systematic literature review to evaluate the utility of PET or PET-CT in evaluation of IIM. MethodsA search of Medline and EMBASE from 1990 to 2022 using keywords related to IIM and PET was performed. English language studies of adults with IIM who had PET or PET-CT were included. ResultsOur search identified 1173 potentially relevant abstracts, 19 of which were included. The majority of studies used [18F] fluorodeoxyglucose (FDG) PET or PET-CT scans, while the remainder used [18F] florbetapir and [11C] Pittsburgh compound B ([11C] PIB). The sensitivity and specificity of 18F-FDG-PET or 18F-FDG-PET-CT for diagnosing malignancy compared with standard detection methods was 66.7–94% and 80–97.8%, respectively. The sensitivity of 18F-FDG PET-CT for ILD was 93–100% when high-resolution CT was used as the reference standard. 18F-PET and 18F-FDG-PET-CT appear to accurately detect muscle inflammation, although correlations with clinical measures of IIM disease activity were variable. [18F] florbetapir PET-CT and [11C] PIB PET were able to differentiate sporadic inclusion body myositis (IBM) from non-IBM IIM. ConclusionPET-CT holds promise as a single tool that can simultaneously evaluate multiple aspects of IIM. These include screening for associated malignancy, achieving an early diagnosis of ILD and evaluating muscle inflammation.

Abnormal paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies.

Patients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein that protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients. A total of 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analysed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes. The arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM-associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes. The arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favourable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.

Low-Density Granulocytes and Neutrophil Extracellular Traps as Biomarkers of Disease Activity in Adult Inflammatory Myopathies.

Biomarkers for disease activity and damage accrual in idiopathic inflammatory myopathies (IIMs) are currently lacking. The purpose of this cross-sectional study is to analyze the relationship among low-density granulocytes (LDGs), neutrophil extracellular traps (NETs), and clinical and immunological features of patients with IIM. We assessed disease activity, damage accrual, amount of LDGs, NETs, expression of LL-37, and serum cytokines in 65 adult patients with IIM. Differences between groups and correlations were assessed by Kruskal-Wallis, Mann-Whitney U, and Spearman ρ tests. The association between LDGs, NETs, disease activity, calcinosis, and cutaneous ulcers was assessed by logistic regression. To address the capacity of LDGs and NETs to diagnose disease activity, we used receiving operating characteristic curves. Low-density granulocytes were higher in patients with active disease, ulcers, calcinosis, and anti-MDA5 antibodies, which correlated with serum levels of IL-17A and IL-18. Neutrophil extracellular traps were higher in patients with calcinosis, elevated titers of antinuclear antibodies, and positive anti-PM/Scl75 tests. The combination of a high proportion of both total LDGs and NETs was associated with the presence of calcinosis and cutaneous ulcers. LL-37 was higher in NETs originating from LDGs. Normal-density neutrophils were elevated in patients with active dermatomyositis. Low-density granulocytes and NETs containing LL-37 are increased in patients with IIM and active disease, and correlate with proinflammatory cytokines. Both total and CD10+ LDGs are potential biomarkers for disease activity and, in combination with NETs, have the potential to detect patients who are at risk for cutaneous ulcers and calcinosis.

Distribution and trajectory of direct and indirect costs of idiopathic inflammatory myopathies

ObjectivesTo estimate the annual direct and indirect costs associated with Idiopathic Inflammatory Myopathies (IIM) over time, including the pre-diagnostic period. MethodsA cohort of incident adult IIM patients (n = 673) was identified from the Swedish National Patient Register from 2010 to 2016 and matched with general population comparators (n = 3343). Follow-up started at IIM diagnosis and corresponding date in the general population. International Classification of Diseases codes (ICD-10) were used for IIM case definition. Costs were calculated using national register data. ResultsThe costs related to IIM started to increase 2 years before diagnosis. In the year following diagnosis, the mean annual IIM cost was €21 639 compared to €4816 in the general population. Five years after diagnosis, the mean annual cost in the IIM cohort was €12 796. Outpatient visits, hospitalizations and productivity loss were the components driving the increment in overall annual disease-related expenditures. Indirect costs accounted for a significant portion of IIM long-term societal costs. The highest costs were found in individuals of working age with cancer-associated IIM. ConclusionsThe mean annual costs in IIM were 3 to 5 times higher than in the general population in the 5-year period following diagnosis. These costs started to increase long before diagnosis, were at their peak in the year post-diagnosis and remained elevated thereafter. Indirect costs contributed to a substantial portion of this increment. Early in the IIM disease course, clinicians and allied health professionals should aim to improve function, reduce damage and address barriers to return-to-work to mitigate these costs.

Defining cardiac involvement in idiopathic inflammatory myopathies: a systematic review.

Recent advances in cardiac MRI (CMR) and other diagnostic techniques have made it easier to identify subclinical cardiac inflammation and dysfunction in the idiopathic inflammatory myopathies (IIM). Herein, we systematically review the literature regarding cardiac involvement in IIM. We searched Medline and EMBASE from 1990 to 2020 using keywords related to IIM and cardiac disease. We included English language studies in adults with any immune-mediated, inflammatory muscle pathology. We identified 10 425 potentially relevant abstracts, of which 29 were included. Most frequently these included patients with PM or DM without symptomatic myocarditis. Five categories of cardiac investigation were used in these patients: cardiac enzyme testing, ECG, transthoracic echocardiography, CMR and nuclear medicine testing. Patients with clinical myocarditis had universally abnormal cardiac troponin levels and ECG. Elevated cardiac troponin T was more common than cardiac troponin I and may correlate with disease activity, whereas cardiac troponin I was more specific for cardiac involvement. Non-specific ECG changes were common. The major finding on transthoracic echocardiography was abnormal ejection fraction. Gross systolic dysfunction was unusual, but subclinical systolic dysfunction was reported in several studies. Abnormal diastolic function was common and may be associated with disease duration. Late gadolinium enhancement (reflecting regional necrosis or scarring) and abnormal myocardial mapping parameters (reflecting myocardial inflammation, fibrosis and oedema) were frequently identified on CMR, suggesting significant subclinical myocardial pathology (despite typically normal ejection fraction). Abnormal cardiac investigations are commonly found in asymptomatic IIM patients, which has potential prognostic and treatment implications.

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.

The aetiopathogenic significance, clinical relevance and therapeutic implications of vasculopathy in idiopathic inflammatory myopathy.

It is 120 years since 'angiomyositis' was included alongside 'polymyositis' and 'dermatomyositis' in an attempt to propose a taxonomy that reflected the major clinical characteristics of idiopathic inflammatory myopathy (IIM). Endothelial injury, perivascular inflammation and capillary loss are important histological findings in affected tissues in IIM. Overt vascular clinical features including RP and abnormal nailfold capillaroscopy (NC) are also common in IIM. Despite the presence of endothelial injury, perivascular inflammation and capillary loss in affected tissues in IIM, and the presence of clinical features such as RP and NC abnormalities, the pathogenic and therapeutic implications of vasculopathy in IIM have been somewhat overlooked. RP and NC abnormalities are not always present, providing a valuable opportunity to explore aetiopathogenic factors driving vasculopathy within autoimmune rheumatic disease. The present review examines the aetiopathogenic, prognostic and therapeutic significance of vasculopathy in IIM. We describe the prevalence and clinical relevance of vasculopathy in IIM, and consider how vasculopathy may be better utilized to support improved IIM diagnosis and disease classification. Areas of unmet research need are highlighted where relevant.

Community-Acquired Pneumonia and Hospital-Acquired Pneumonia in Adult Patients with Idiopathic Inflammatory Myopathy: Outcome and Antibiotic Therapy.

IntroductionCommunity-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) are common complications in idiopathic inflammatory myopathy (IIM) patients, and are frequently associated with unfavorable outcome as well as prolonged antibiotic therapy. In this study, we intended to clarify whether clinical pulmonary infection score (CPIS) and multiple serum biomarkers are valuable in predicting unfavorable outcomes and prolonged antibiotic therapy in adult IIM patients complicated with CAP or HAP.MethodsData of IIM patients with CAP or HAP who were admitted to three tertiary centers from December 2010 to November 2019 were retrospectively collected. Cox proportional hazards regression analysis and logistic regression analysis were adopted to identify risk factors for unfavorable outcomes and prolonged antibiotic therapy in these patients. The predictive values of potential predictors were assessed using receiver operating characteristic analysis.ResultsThe mortality rate was 60.6% in 109 IIM patients complicated with CAP or HAP. Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT) score, CPIS and timely adjustment to antibiotics based on drug susceptibility test (DST-based antibiotic) were significantly associated with long-term outcome in these patients. With an optimal cutoff value of 6.5 and area under the curve (AUC) of 0.813, CPIS was a more satisfying predictor compared with MYOACT score. The peak C-reactive protein (CRP) level, DST-based antibiotics, and complication of interstitial lung disease (ILD) were also significantly correlated with prolonged antibiotic therapy.ConclusionsIIM patients complicated with CAP or HAP frequently suffer from unfavorable outcomes. Compared with IIM disease activity, CPIS worked as a better predictor of outcome in these patients. Also, the peak CRP level during hospitalization might be valuable in predicting prolonged antibiotic therapy. The existence of ILD might impede early discontinuation of antibiotics. Timely adjustment to antibiotics based on drug susceptibility testing would decrease the mortality rate and reduce the incidence of prolonged antibiotic therapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-020-00268-7.

Patient insights on living with idiopathic inflammatory myopathy and the limitations of disease activity measurement methods \u2013 a qualitative study

BackgroundThe idiopathic inflammatory myopathies (IIMs) are chronic autoimmune conditions, typically resulting in proximal muscle weakness and impacting upon quality of life. Accurate measurement of IIM disease activity is imperative for appropriate medical management and carrying out valid clinical trials. The International Myositis Assessment and Clinical Studies Group (IMACS) “Disease Activity Core Set Measures” are the current gold-standard of IIM disease activity assessment. Anecdotally, patients with an IIM report that the IMACS Core Set Measures and other available methods do not necessarily capture their perceived disease activity. Investigating the patient experiences of living with an IIM and their views on the accuracy of the IMACS Core Set Measures will provide valuable insights for both clinical and research purposes.MethodsEighteen interviews with patients with an IIM were carried out and analysed thematically, using a grounded theory approach. Experiences on living with an IIM and perceptions on the accuracy of disease activity measurement methods were explored.ResultsInterview analysis revealed four themes: 1) fatigue, 2) pain, 3) day-to-day symptom variation, 4) limitations of creatine kinase levels and manual muscle testing.ConclusionsThis study has provided valuable insights into patient experiences of living with an IIM. Aspects of IIM disease activity perceived not to be wholly measured by the IMACS Core Set Measures have also been identified. These findings have implications for future IIM clinical care and research, in particular providing justification for research into pain, fatigue and symptom variation.

Evaluation of a New Skeletal Troponin I Assay in Patients with Idiopathic Inflammatory Myopathies.

The current biomarkers for diagnosis and monitoring of injured and diseased skeletal muscles, such as creatine kinase (CK), have limited tissue specificity and incapability to differentiate between pathological and physiological changes. Thus, new biomarkers with improved diagnostic accuracy are needed. Our aim was to develop and validate a novel assay for skeletal troponin I (skTnI), and to assess its clinical performance in patients with idiopathic inflammatory myopathies (IIM). A two-step fluoroimmunoassay was used to analyze samples from healthy reference individuals (n = 140), patients with trauma (n = 151), and patients with IIM (n = 61). The limit of detection was 1.2 ng/mL, and the upper reference limit (90th percentile) was 5.2 ng/mL. The median skTnI concentrations were <limit of detection (LoD), 2.7 ng/mL, and 8.6 ng/mL in reference, trauma, and IIM cohorts, respectively. Differences in measured skTnI levels were statistically significant between all three study cohorts (Kruskal-Wallis P < 0.001; Mann-Whitney P < 0.001 for all). skTnI and CK had a strong positive correlation (Spearman's r = 0.771, P < 0.001), and the longitudinal changes in skTnI mirrored those observed with CK. With the skTnI assay, patients with IIM were identified from healthy individuals and from patients with traumatic muscular injuries. When compared to CK, skTnI appeared to be more accurate in managing patients with low-grade IIM disease activities. The developed assay serves as a reliable analytical tool for the assessment of diagnostic accuracy of skTnI in the diagnosis and monitoring of myopathies.

Neutrophil dysregulation is pathogenic in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are characterized by muscle inflammation and weakness, myositis-specific autoantibodies (MSAs), and extramuscular organ damage. The role of neutrophil dysregulation and neutrophil extracellular traps (NETs) in IIM is unclear. We assessed whether pathogenic neutrophil subsets (low-density granulocytes [LDGs]) and NETs were elevated in IIM, associated with clinical presentation and MSAs, and their effect on skeletal myoblasts and myotubes. Circulating NETs and LDGs were quantified and correlated with clinical measures. Specific MSAs were tested for their ability to induce NETs. NETs and neutrophil gene expression were measured in IIM biopsies. Whether NETs damage skeletal myoblasts and myotubes was tested. Circulating LDGs and NETs were increased in IIM. IIM LDGs had an enhanced ability to form NETs. LDGs and NETs correlated with IIM disease activity and muscle damage. The serum MSA anti-MDA5 correlated with circulating and tissue NETs and directly enhanced NET formation. An enhanced neutrophil gene signature was present in IIM muscle and associated with muscle injury and tissue IFN gene signatures. IIM NETs decreased the viability of myotubes in a citrullinated histone-dependent manner. Dysregulated neutrophil pathways may play pathogenic roles in IIM through their ability to directly injure muscle cells and other affected tissues.

A novel autoantibody targeting calreticulin is associated with cancer in patients with idiopathic inflammatory myopathies.

ObjectivesTo investigate the prevalence and clinical significance of anti‐calreticulin autoantibodies (anti‐CRT Ab) in a large cohort of idiopathic inflammatory myopathy (IIM) patients.MethodsSera from 469 patients with IIM, 196 patients with other connective tissue diseases, 28 patients with solid tumors and 81 healthy controls were screened for anti‐CRT Ab by enzyme‐linked immunosorbent assay using human recombinant CRT protein. Sera from 35 IIM patients were tested using an immunoprecipitation assay to confirm the presence of anti‐CRT Ab. Subsequently, IIM–cancer patients were identified and divided into new‐onset, remission and recurrent groups based on their cancer status. The relationships between anti‐CRT Ab levels and IIM disease activity were also investigated.ResultsSerum anti‐CRT Ab was detected positive in 81 of the 469 (17.3%) IIM patients. Immunoprecipitated bands were observed at a molecular weight of 60 kDa corresponding to the CRT protein. The IIM patients with anti‐CRT Ab more frequently had cancers compared to the patients without anti‐CRT Ab. Moreover, the prevalence of anti‐CRT Ab differed according to the cancer status. The IIM patients with recurrent cancers had a much higher prevalence of anti‐CRT Ab than those with cancers in remission. Also, serum anti‐CRT Ab levels positively correlated with disease activity at baseline and at follow‐up visits.ConclusionWe report the existence of serum anti‐CRT Ab in IIM patients and demonstrate the possible association of anti‐CRT Ab with malignancy in IIM patients. Serum anti‐CRT Ab could serve as a novel candidate marker of cancer in IIM patients.

Clinical Characteristics of Anti-3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Antibodies in Chinese Patients with Idiopathic Inflammatory Myopathies.

ObjectiveThe objective of this study was to detect the prevalence of anti-3-hydroxyl-3- methylglutaryl coenzyme A reductase (anti-HMGCR) antibodies in Chinese patients with idiopathic inflammatory myopathies (IIMs), and to analyze the clinical features of the antibody-positive IIM patients.MethodsThe presence of anti-HMGCR antibodies was detected in 405 patients with IIMs, 90 healthy controls, and 221 patients with other rheumatic diseases by using an ELISA kit. Clinical data from anti-HMGCR antibody-positive and -negative patients were compared. Long-term follow-up of the anti-HMGCR antibody-positive patients was conducted to evaluate the role of anti-HMGCR antibody in IIM disease prognosis.ResultsOf the 405 IIM patients, 22 (5.4%) were found to carry the anti-HMGCR antibody. These IIM patients were predominantly female (73%), and only 3 anti-HMGCR antibody-positive patients with IIM were exposure to statins. Most patients experienced progressive onset, and presented with muscular weakness. Dysphagia was observed in half of the patients (p < 0.01), and 15% of these patients experienced the complication of interstitial lung disease (ILD) (p > 0.05). Mean creatine kinase (CK) levels were higher in antibody-positive patients than in antibody-negative patients (p < 0.05). Muscle biopsies were available from 12 anti-HMGCR antibody-positive patients, eight who experienced myofiber necrosis and showed very little or no evidence of inflammatory cell infiltrates in their muscle biopsies. Of these eleven patients who were followed-up 2.5- to 29-month, 73% experienced improvement after treatment. A cross-sectional study showed that anti-HMGCR antibody levels were significantly associated with CK levels (r = 0.486, p = 0.026) as well as with Myositis Disease Activity Assessment (MYOACT) scores (r = -0.67, p = 0.003) during the initial visit. However, changes in serum anti-HMGCR antibody levels did not correlate with changes in CK levels, Manual Muscle Testing 8 (MMT-8) scores or MYOACT scores in long-term follow-up.ConclusionThe major clinical features of anti-HMGCR antibody-positive Chinese IIM patients were muscle weakness and dysphagia, which were seen in patients with and without statin exposure. This subtype of patients were responsive to immunosuppressive treatment and received good prognoses after treatment, but serum levels of the anti-HMGCR antibody do not correlate with disease activity.

Recent advances in the immunogenetics of idiopathic inflammatory myopathy

This review summarizes the previous and current literature on the immunogenetics of idiopathic inflammatory myopathy (IIM) and updates the research progress that has been made over the past decade. A substantial part of the genetic risk for developing adult- and juvenile-onset IIM lies within the major histocompatibility complex (MHC), and a tight relationship exists between individual human leukocyte antigen alleles and specific serological subtypes, which in turn dictate clinical disease phenotypes. Multiple genetic regions outside of the MHC are increasingly being identified in conferring IIM disease susceptibility. We are still challenged with the task of studying a serologically and clinically heterogeneous disorder that is rarer by orders of magnitude than the likes of rheumatoid arthritis. An ongoing and internationally coordinated IIM genome-wide association study may provide further insights into IIM immunogenetics.

An update on the immunogenetics of idiopathic inflammatory myopathies: major histocompatibility complex and beyond

To update the reader on immunogenetic advances in idiopathic inflammatory myopathy (IIM) over the past 18 months. In Caucasian IIM, despite a shared association with the human leukocyte antigen (HLA) 8.1 ancestral haplotype (HLA-DRB1*03-DQA1*05-DQB1*02), anti-Jo-1 and anti-PM-Scl antibody-positive cases have differing IIM clinical phenotypes. A study of the HLA-DPB1 region has shown that DPB1*0101 is associated with anti-Jo-1 positivity but not with anti-PM-Scl. IIM single nucleotide polymorphism studies have demonstrated associations in the protein tyrosine phosphatase, nonreceptor type 22, tumour necrosis factor alpha and interleukin-1 genes. The GM 13 allotype has been confirmed as a risk factor in Caucasian IIM. In inclusion body myositis, the HLA 8.1 ancestral haplotype may not only influence disease susceptibility but also disease expression. A follow-up study including a meta-analysis of the apolipoprotein E gene in inclusion body myositis suggests that this gene does not confer risk of disease. Although a substantial part of the genetic risk for developing adult and juvenile IIM lies within the major histocompatibility complex, recent research suggests that genetic regions outside of the major histocompatibility complex are also potentially involved in conferring IIM disease susceptibility, although with more modest effect sizes. An ongoing and internationally coordinated IIM genome-wide association scan may provide further insights into IIM immunogenetics.

Have recent immunogenetic investigations increased our understanding of disease mechanisms in the idiopathic inflammatory myopathies?

The idiopathic inflammatory myopathies (IIM) continue to provide a challenge given the variable effectiveness of the available treatments, and immunogenetic studies are ongoing to further elucidate IIM disease mechanisms. This review examines how recent research has improved our understanding of the mechanisms that lead to IIM. HLA-DRB1 studies in a large homogenous cohort of UK Caucasian patients have confirmed that polymyositis (PM) and dermatomyositis (DM) are not genetically identical diseases while other studies have shown that tumor necrosis factor alpha is genetically implicated in disease susceptibility. Some remarkable results from an international collaboration, correlating gene-environment interactions, clearly suggest that ultraviolet light is capable of modulating both clinical and immunologic features of IIMs. Studies on microchimerism are unraveling interesting associations in juvenile DM patients, and bolstering the hypothesis that myositis may be an 'allo-immune' disease. mRNA gene expression profiling is helping to increase our understanding of myositis pathogenesis, whilst animal models have provided new information on the roles of Th1 responses and nitric oxide synthase in muscle disease. New candidate genes have been examined in inclusion body myositis (IBM), and a novel gene transfer experiment has been conducted, which led to significant changes in expression of the IBM phenotype. Improving the understanding of the immunogenetics and immunopathogenesis of the IIMs may in the future provide novel therapeutic targets, and thus improve outcomes in these difficult diseases.