Idiopathic Inflammatory Myopathies Patients Research Articles

Assessment of antibody levels to SARS-CoV-2 in patients with idiopathic inflammatory myopathies receiving treatment with intravenous immunoglobulin

Antibodies to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) have been reported in pooled healthy donor plasma and intravenous immunoglobulin products (IVIG). It is not known whether administration of IVIG increases circulating anti-SARS-CoV-2 antibodies (COVID ab) in IVIG recipients. COVID ab against the receptor binding domain of the spike protein were analyzed using a chemiluminescent microparticle immunoassay in patients with idiopathic inflammatory myopathies (IIM) both receiving and not receiving IVIG (IVIG and non-IVIG group, respectively). No significant differences in COVID ab levels were noted between IVIG and non-IVIG groups (417 [67–1342] AU/mL in IVIG vs 5086 [43–40,442] AU/mL in non-IVIG, p = 0.11). In linear regression models including all post-vaccination patient samples, higher number of vaccine doses was strongly associated with higher COVID ab levels (2.85 [1.21, 4.48] log AU/mL, regression coefficient beta [95% CI], p = 0.001), while use of RTX was associated with lower ab levels (2.73 [− 4.53, − 0.93] log AU/mL, beta[95%CI], p = 0.004). In the IVIG group, higher total monthly doses of IVIG were associated with slightly higher COVID ab levels (0.02 [0.002–0.05] log AU/mL, p = 0.04). While patients on IVIG did not have higher COVID ab levels compared to the non-IVIG group, higher monthly doses of IVIG were associated with higher circulating levels of COVID ab in patients receiving IVIG, particularly in patients concomitantly receiving RTX. Our findings suggest that IIM patients, especially those at increased risk of COVID infection and worse COVID outcomes due to RTX therapy may have protective benefits when on concurrent IVIG treatment.

Long-term safety of COVID vaccination in individuals with idiopathic inflammatory myopathies: results from the COVAD study

Limited evidence on long-term COVID-19 vaccine safety in patients with idiopathic inflammatory myopathies (IIMs) continues to contribute to vaccine hesitancy. We studied delayed-onset vaccine adverse events (AEs) in patients with IIMs, other systemic autoimmune and inflammatory disorders (SAIDs), and healthy controls (HCs), using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. A validated self-reporting e-survey was circulated by the COVAD study group (157 collaborators, 106 countries) from Feb–June 2022. We collected data on demographics, comorbidities, IIM/SAID details, COVID-19 history, and vaccination details. Delayed-onset (> 7 day) AEs were analyzed using regression models. A total of 15165 respondents undertook the survey, of whom 8759 responses from vaccinated individuals [median age 46 (35–58) years, 74.4% females, 45.4% Caucasians] were analyzed. Of these, 1390 (15.9%) had IIMs, 50.6% other SAIDs, and 33.5% HCs. Among IIMs, 16.3% and 10.2% patients reported minor and major AEs, respectively, and 0.72% (n = 10) required hospitalization. Notably patients with IIMs experienced fewer minor AEs than other SAIDs, though rashes were expectedly more than HCs [OR 4.0; 95% CI 2.2–7.0, p < 0.001]. IIM patients with active disease, overlap myositis, autoimmune comorbidities, and ChadOx1 nCOV-19 (Oxford/AstraZeneca) recipients reported AEs more often, while those with inclusion body myositis, and BNT162b2 (Pfizer) recipients reported fewer AEs. Vaccination is reassuringly safe in individuals with IIMs, with AEs, hospitalizations comparable to SAIDs, and largely limited to those with autoimmune multimorbidity and active disease. These observations may inform guidelines to identify high-risk patients warranting close monitoring in the post-vaccination period.

Plasma pentraxin 3 in idiopathic inflammatory myopathies: a possible new biomarker of disease activity.

Pentraxin-3 (PTX3) is a component of humoral innate immunity with essential functions both in promotion and resolution of inflammation. We aimed to study the PTX3 in the plasma and in the muscle of patients with idiopathic inflammatory myopathies (IIM) and whether PTX3 may correlate with disease activity. Plasma PTX3 levels were assessed in 20 patients with IIMs, 10 dermatomyositis (DM), and 10 polymyositis (PM), compared to 10 patients with rheumatoid arthritis (RA) and 10 healthy donors (HDs) aged, sex, and body mass index matched. Disease activity in IIMs was assessed by Myositis Disease Activity Assessment Visual Analog Scale (MYOACT), while disease activity score on 28 joints (DAS28) was used for RA patients. Muscle histopathology and immunohistochemical (IHC) analyses were also performed. Mean plasma PTX3 levels were significantly higher in IIM patients than HDs (518 ± 260 pg/ml vs. 275 ± 114 pg/ml, P = 0.009). Linear regression analysis adjusted for age, sex, and disease duration showed a direct correlation between PTX3 and CPK levels (β: 0.590), MYOACT (β: 0.759), and physician global assessment of disease activity (β: 0.832) in IIMs. No association between PTX3 levels and DAS28 was found in RA. Global PTX3 pixel fraction was higher in IIM than HDs muscle, but a lower PTX3 expression was found in perifascicular areas of DM and in myofibers with sarcolemmal staining for membrane attack complement. PTX3 plasma levels were increased in IIMs and correlated with disease activity suggesting a possible role as biomarker of disease activity. PTX3 showed a different distribution in DM or PM muscle.

Cardiovascular risk in myositis patients compared with the general population.

We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features. Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications. Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients. Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC.

P.038 Idiopathic inflammatory myopathies and malignancy screening: a survey of the current practices amongst Canadian neurologists and rheumatologists

Background: There is a well-established association between idiopathic inflammatory myopathies (IIM) and malignancy. There are no evidence-based guidelines amongst neurologists and rheumatologists on the choice and timing of malignancy investigations. Our aim is to characterize the current gaps and uncertainties amongst neurologists and rheumatologists with malignancy screening in IIM patients. Methods: An online survey consisting of 18 multiple-choice questions related to IIM malignancy screening was distributed to adult neurologists and rheumatologists in Canada. Quantitative and descriptive analysis was performed. Results: The majority of respondents (96%, n=68) performed malignancy screening. There was variability in practice including delegation and choice of screening tests, influence of patient-specific factors, and time and length of repeat testing. Only 18% of respondents were confident in their malignancy screening practices. Between neurologists and rheumatologists, there were differences in the number of IIM patients seen, consideration of patient-specific factors and choice of screening investigations. Further details and data will be presented at the conference. Conclusions: There is a lack of consensus and confidence in the choice and timing of malignancy investigations in IIM, with neurologists and rheumatologists differing in their approaches. Further research is required to better understand the relationship between IIM and malignancy to create expert-led consensus guidelines.

Immunological Pathways in Sarcoidosis and Autoimmune Rheumatic Disorders-Similarities and Differences in an Italian Prospective Real-Life Preliminary Study.

The pathogenesis of sarcoidosis involves T cells and B lymphocytes that produce autoantibodies. We compared the expression of different T and B cell subsets in sarcoidosis and three B-mediated rheumatic diseases that can affect the lungs in an attempt to identify similarities and differences that distinguish these diseases. The study included patients referred to Siena University Hospital's respiratory disease and rheumatology units. Patients were enrolled prospectively and consecutively. Healthy volunteers were also included. Multicolor flow cytometry was performed on phenotype T and B cell subsets. Multivariate analysis was carried out to reduce the dimensionality of the data. Fifteen patients had a diagnosis of sarcoidosis, fourteen idiopathic inflammatory myopathies (IIM), five granulomatosis with polyangiitis (GPA), ten microscopic polyangiitis (MPA), and seven were controls. Thirty-five T and B cell subsets were phenotyped, 15 of which were significantly different in sarcoidosis, B-mediated rheumatic disorders, and controls. Principal components analysis distinguished the four groups of patients with a total explained variance of 54.7%. A decision tree was constructed to determine which clustering variables would be most useful for distinguishing sarcoidosis, IIM, MPA, and GPA. The model showed regulatory T helper cells (Th-reg) > 5.70% in 91% of sarcoidosis patients as well as Th-reg ≤ 5.70 and Th17 > 43.27 in 100% of MPA. It also showed Th-reg ≤ 5.70, Th17 ≤ 43.27 and Tfh-reg ≥ 7.81 in 100% of GPA patients, and Th-reg ≤ 5.70, Th17 ≤ 43.27 and Tfh-reg ≤ 7.81 in 100% of IIM patients. The immune cell profile sheds light on similarities and differences between sarcoidosis and B-mediated rheumatic diseases. Sarcoidosis and autoimmune diseases show similar patterns of cellular immune dysregulation, suggesting a common pathogenic pathway that may provide an opportunity for further understanding autoimmunity and exploring biological therapies to treat sarcoidosis.

The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk.

Framingham risk score (FRS), systematic coronary risk evaluation (SCORE), the 10-year atherosclerotic cardiovascular disease risk algorithm (ASCVD), and their modified risk scores are the most common cardiovascular risk scores. The aim of this case-control study was to evaluate the performance of cardiovascular risk scores in detecting carotid subclinical atherosclerosis (SCA) in patients with idiopathic inflammatory myopathies (IIMs). A total of 123 IIMs patients (71.5% female, mean age 50 ± 14 years) and 123 age- and gender-matched healthy controls were included in this study. Carotid SCA was more prevalent in IIMs patients compared with controls (77.2 vs 50.4%, P < 0.001). Moreover, patients with carotid SCA+ had older age, and all risk scores were significantly higher in IIMs patients with SCA+ compared to subjects with SCA- (all P < 0.001). According to FRS, SCORE, and ASCVD risk scores, 77.9, 96.8, and 66.7% patients with SCA+ were classified as low risk category, respectively. The modified scores also demonstrated a modest improvement in sensitivity. Notably, by adopting the optimal cutoff values, these risk scores had good discrimination on patients with SCA+, with area under curves of 0.802-0.893. In conclusion, all cardiovascular risk scores had a poor performance in identifying IIMs patients at high cardiovascular risk.

CCL18 as a Biomarker of Interstitial Lung Disease (ILD) and Progressive Fibrosing ILD in Patients with Idiopathic Inflammatory Myopathies.

To assess CCL18 and OX40L as biomarkers of interstitial lung disease (ILD) and/or progressive fibrosing (PF-) ILD in idiopathic inflammatory myopathies (IIMs). Patients with IIMs seen in our center from July 2020 to March 2021 were consecutively enrolled. ILD was detected by high-resolution CT. CCL18 and OX40L serum levels were measured by validated ELISA assays in 93 patients and 35 controls. At the 2-year follow-up, PF-ILD was evaluated according to the INBUILD criteria. ILD was diagnosed in 50 (53.7%) patients. CCL18 serum levels were higher in IIMs patients vs. controls (232.9 [IQR 134.7-399.07] vs. 48.4 [29.9-147.5], p < 0.0001), with no difference for OX40L. IIMs-ILD patients exhibited higher levels of CCL18 than those without ILD (306.8 [190.8-520.5] vs. 162 [75.4-255.8], p < 0.0001). High CCL18 serum levels were independently associated with IIMs-ILD diagnosis. At follow-up, 22/50 (44%) patients developed a PF-ILD. Patients who developed PF-ILD had higher CCL18 serum levels than non-progressors (511 [307-958.7] vs. 207.1 [149.3-381.7], p < 0.0001). Multivariate logistic regression analysis revealed CCL18 as the only independent predictor of PF-ILD (OR 1.006 [1.002-1.011], p = 0.005). Although in a relatively small sample, our data suggest that CCL18 is a useful biomarker in IIMs-ILD, particularly in the early identification of patients at risk of developing PF-ILD.

The Efficacy and Safety of Rituximab in Patients with Idiopathic Inflammatory Myopathy-Associated Interstitial Lung Disease: Case Series.

Idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD) is often rapidly progressive with a poor prognosis; however, no standard therapeutic regimen has been identified. This study aimed to investigate the efficacy and safety of rituximab in IIM-ILD patients. Five patients who had been administered rituximab for IIM-ILD at least once between August 2016 and November 2021 were included. Lung function decline was compared one year before and after rituximab. Disease progression, defined as a greater than 10% relative decline in forced vital capacity (FVC) compared to the baseline, was also compared before and after treatment. Adverse events were recorded for safety analysis. Five IIM-ILD patients received eight cycles. FVC-predicted values significantly decreased from 6 months before rituximab administration to those at the baseline (54.1% predicted (pre-6 months) vs. 48.5% predicted (baseline), p = 0.043); however, the FVC decline stabilized after rituximab. The rate of disease progression before rituximab showed a tendency to decrease after rituximab (75% (before) vs. 12.5% (6 months after, p = 0.059) vs. 14.3% (12 months after, p = 0.102)). Three adverse events developed, but none resulted in death. Rituximab can stabilize lung function decline with tolerable safety in Korean IIM patients with refractory ILD.

Plasma proteomic profiling reveals KRT19 could be a potential biomarker in patients with anti-MDA5+ dermatomyositis.

To investigate the immune response-related protein profiling in plasma of patients with idiopathic inflammatory myopathies (IIMs), especially in anti-MDA5+ dermatomyositis (DM). A total of 166 IIM patients and 107 healthy controls (HCs) were enrolled in our study. Ninety-two plasma immune response-related proteins were detected by Olink proteomics in 36 IIM patients and 25 HCs. The expression of plasma KRT19 was validated in another 130 IIM patients, 82 HCs, and 55 other rheumatic diseases. A total of 46 differentially expressed proteins were detected, including 12 upregulated proteins and 34 downregulated proteins in IIM patients compared with HCs. Pathway analysis revealed lactoferrin danger signal response pathway, TLR4 signaling and tolerance, infection, and IL-10 signaling pathway were activated. The immune response-related protein profiling significantly altered in anti-MDA5+ DM patients, with LAMP3, HSD11B1, and KRT19 significantly increased, while SH2D1A, ITGA11, TRIM21, CD28, ITGB6, and HEXIM1 tremendously decreased. In addition, KRT19 was significantly increased in IIM patients, especially in anti-MDA5+ DM patients with the diagnostic value of a significant area under the ROC curve of 0.881. Immune response-related proteins are significantly altered in patients with anti-MDA5+ DM patients. KRT19 could be a potential biomarker for anti-MDA5+ DM patients. Key Points • What is already known on this topic? Anti-MDA5+ DM is a distinctive subtype of IIM. Plasma immune response-related proteins panel needs to be investigated. • What this study adds? Plasma protein profiling of immune response-related proteins significantly altered in patients with idiopathic inflammatory myopathies (IIM), especially in anti-MDA5+ DM patients. • How this study might affect research, practice, or policy? KRT19 could be a potential biomarker in patients with anti-MDA5+ dermatomyositis.

Type 1 interferon signature in peripheral blood mononuclear cells and monocytes of idiopathic inflammatory myopathy patients with different myositis-specific autoantibodies.

Myositis-specific autoantibodies (MSAs) are clinically used to diagnose and define idiopathic inflammatory myopathy (IIM) subsets. However, the underlying pathogenic mechanisms of patients with different MSAs remain unclear. A total of 158 Chinese patients with IIM and 167 gender- and age-matched healthy controls (HCs) were enrolled. Transcriptome sequencing (RNA-Seq) was performed with peripheral blood mononuclear cells (PBMCs), followed by the identification of differentially expressed genes (DEGs) and analysis of gene set enrichment analysis, immune cell infiltration, and WGCNA. Monocyte subsets and related cytokines/chemokines were quantified. The expressions of interferon (IFN)-related genes were validated using qRT-PCR and Western blot in both PBMCs and monocytes. We also performed correlation analysis and ROC analysis to explore the potential clinical significance of the IFN-related genes. There were 1,364 genes altered in patients with IIM, including 952 upregulated and 412 downregulated genes. The type I interferon (IFN-I) pathway was remarkably activated in patients with IIM. Compared with patients with other MSAs, IFN-I signatures were significantly activated in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. In total, 1,288 hub genes associated with IIM onset were identified using WGCNA, including 29 key DEGs associated with IFN signaling. The patients had more CD14brightCD16- classical, CD14brightCD16+ intermediate, and fewer CD14dimCD16+ non-classical monocyte subsets. Plasma cytokines like IL-6 and TNF and chemokines including CCL3 and MCPs increased. The validation of IFN-I-related gene expressions was consistent with the findings from RNA-Seq. The IFN-related genes were correlated with laboratory parameters and helpful for IIM diagnosis. Gene expressions were remarkably altered in the PBMCs of IIM patients. Anti-MDA5+ IIM patients had a more pronounced activated IFN signature than others. Monocytes exhibited a proinflammatory feature and contributed to the IFN signature of IIM patients.

Double Negative B cells are decreased in patients with Idiopathic Inflammatory Myopathies.

Abstract Background: Idiopathic inflammatory myopathies (IIM) are systemic autoimmune diseases characterized by skeletal muscle inflammation, frequently accompanied by extra muscular features associated with specific autoantibodies. The detailed pathogenesis of IIM remains unclear, but evidence suggests autoreactive B cells may play an essential role in this process. However, little is known about changes in peripheral blood B cell subsets in adult IIM patients. Objective: This study aims to determine the frequency of B cell subsets among patients with IIM and their clinical correlation with disease activity. Methods: Using a multiparametric flow cytometric approach, we determined the frequencies of B cell subsets in a cohort of 36 patients with IIM and correlated their values with clinical and laboratory data. Results: DN B cells (CD27 −IgD −), which represent an atypical B cell subset associated with various autoimmune diseases, showed a significant decrease in frequencies and a correlation with the MMT8 score. Within the DN subset, the DN1 subpopulation (CD21 +CD11c −) showed a significant decrease compared to the control group. There was also a significant decrease in the memory B cell subpopulation (CD27 +CD38 −) and the non-classic memory B cell subpopulation (CD27 −CD38 −CD24 +). A significant increase in naive B cells (CD27 −IgD +) was observed. However, none of the previously described subpopulations correlated with clinical features. Conclusion: This study demonstrated a decrease in frequencies in the double negative B cell subset in adult IIM patients and showed a correlation with clinical features, which suggests that these B cells could be related to disease activity. UNAM-DGAPA-PAPIIT IN212122

The Emerging Role of Mitochondrial Dysfunction in the Pathogenesis of Idiopathic Inflammatory Myopathies.

Increasing evidence points towards mitochondria as crucial players in the initiation and progression of auto-immune and degenerative disorders, to which impaired cell metabolism is but a facet of the subjacent etiopathogenesis. This review aims to introduce the reader to essential concepts of mitochondrial abnormalities in idiopathic inflammatory myopathy (IIM), underscoring inclusion-body myositis and dermatomyositis. Far surpassing the initial simplistic view of being responsible for energy generation, mitochondria have gathered attention regarding their role in inflammatory processes, being able to fuel autoimmunity, as shown by the presence of anti-mitochondrial antibodies (AMAs) in up to 10% of IIM patients. As cellular respiration takes place, mitochondrial metabolites might help to shape the pro-inflammatory milieu in affected muscle, beyond generating reactive oxygen species, which are well-recognized inducers of damage-associated molecular patterns. A series of mitochondrial components might facilitate the sterile activation of pro-inflammatory cells and the production of several cytokines responsible for enhancing auto-immune responses. Marked variation in the mitochondrial genome has also been reported in IIM patients. As such, we summarize key historical and recent advances linking aberrations and instabilities of mitochondrial DNA to impaired muscle function. Besides discussing mitochondrial dysfunction as an essential part of IIM development, we also highlight possible associations between presence of AMAs and a particular phenotype of IIM, with its own characteristic clinical and radiological pattern. Finally, we present promising treatment approaches targeting mitochondria, while briefly discussing experimental models for gaining deeper insight into the disease process, and ultimately leading to novel drug development.

Idiopathic Inflammatory Myopathies and Malignancy Screening: A Survey of the Current Practices Amongst Canadian Neurologists and Rheumatologists (P9-8.006)

<h3>Objective:</h3> To better understand and characterize the current gaps and uncertainties amongst neurologists and rheumatologists in Canada with regards to malignancy screening in patients with idiopathic inflammatory myopathies (IIM). <h3>Background:</h3> There is a well-established association between IIM and underlying malignancy. Amongst IIM patients, the need for malignancy screening is generally accepted, however there are no evidence-based guidelines amongst neurologists and rheumatologists to guide clinicians on the choice and timing of investigations. <h3>Design/Methods:</h3> An online survey was created using Microsoft Office Forms consisting of 18 multiple-choice questions related to IIM malignancy screening practice. The survey contained questions pertaining to respondent characteristics, malignancy screening practices and concerns surrounding these practices. The survey was distributed to adult neurologists and rheumatologists in Canada through several local and country-wide neurology and rheumatology organizations. Quantitative and descriptive analysis of the data was performed using Excel and statistical software programs. <h3>Results:</h3> There were 68 respondents. Majority of respondents (96%) performed malignancy screening, however there was variability in many aspects of practice including delegation and choice of screening tests, influence of patient-specific factors, and time and length of repeat testing. Only 18% of respondents were confident in their malignancy screening practices. The most significant perceived knowledge gap was lack of consensus or guidelines on choice and frequency of malignancy screening. Between neurologists and rheumatologists, there were differences in the number of IIM patients seen, consideration of patient-specific factors and choice of screening investigations. <h3>Conclusions:</h3> Variability and knowledge gaps exist amongst neurologists and rheumatologists with regards to malignancy screening in IIM patients, especially timing and need for repeat screening. There is a lack of consensus and confidence in the choice and timing of these investigations, with neurologists and rheumatologists differing in their approach to malignancy screening. Further research is required to better understand the relationship between IIM and malignancy to create expert-led consensus guidelines. <b>Disclosure:</b> Dr. Jekielek has nothing to disclose. Dr. Nisenbaum has nothing to disclose. Dr. Vinik has nothing to disclose. Dr. Kassardjian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Kassardjian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Kassardjian has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.

The diagnostic value of sST2 for myocardial fibrosis in idiopathic inflammatory myopathies in subclinical stage of cardiac involvement.

Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P < 0.01), respectively. sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.

Diagnostic Yield of Computed Tomography for Cancer Detection in a Tertiary Referral Population of Idiopathic Inflammatory Myositis Patients.

To inform guidance for cancer detection in patients with idiopathic inflammatory myopathy (IIM), we evaluated the diagnostic yield of computed tomography (CT) imaging for cancer screening/surveillance within distinct IIM subtypes and myositis-specific autoantibody strata. We conducted a single-center, retrospective cohort study in IIM patients. Overall diagnostic yield (number of cancers diagnosed/number of tests performed), percentage of false positives (number of biopsies performed not leading to cancer diagnosis/number of tests performed), and test characteristics were determined on CT of the chest and abdomen/pelvis. Within the first 3 years since IIM symptom onset, a total of 9 of 1,011 (0.9%) chest CT scans and 12 of 657 (1.8%) abdomen/pelvis CT scans detected cancer. Diagnostic yields for both CT of the chest and CT of the abdomen/pelvis were highest in dermatomyositis, specifically anti-transcription intermediary factor 1γ (2.9% and 2.4% for CT of the chest and abdomen/pelvis, respectively). The highest percentage of false positives was in patients with antisynthetase syndrome (ASyS) (4.4%) and immune-mediated necrotizing myopathy (4.4%) on CT of the chest, and ASyS (3.8%) on CT of the abdomen/pelvis. Patients ages <40 years old at IIM onset had both low diagnostic yields (0% and 0.5%) and high false-positive rates (1.9% and 4.4%) for CT of the chest and abdomen/pelvis, respectively. In a tertiary referral cohort of IIM patients, CT imaging has a wide range of diagnostic yield and frequency of false positives for contemporaneous cancer. These findings suggest that cancer detection strategies targeted according to IIM subtype, autoantibody positivity, and age may maximize cancer detection while minimizing the harms and costs of over-screening.

Elevated serum soluble CD27 levels are associated with both disease activity and humoral immune activity in patients with rheumatoid arthritis.

To investigate the serum level of soluble CD27 (sCD27) and its potential clinical significance in rheumatoid arthritis (RA). Serum sCD27 levels in RA patients, idiopathic inflammatory myopathy (IIM) patients, systemic lupus erythematosus (SLE) patients and healthy controls (HCs) were detected by enzyme-linked immunosorbent assay. The medical information and laboratory data of the patients were collected. Serum sCD27 levels in RA patients with different clinical features were analysed, as was the correlation between the clinical data and serum sCD27 levels. Independent samples t test, the Mann-Whitney U-test or Wilcoxon signed-rank test, and Spearman correlation were used for statistical analysis. Levels of sCD27 were elevated in RA patients (3898 [2525, 5834] pg/mL) compared with IIM patients (2467 [1939, 3324] pg/mL) or HCs (1659 ± 648 pg/mL) (p 0.001). In addition, serum sCD27 levels correlated with age, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A, immunoglobulin G, complement 4 and disease activity score in 28 joints in RA patients. Levels of sCD27 were higher in RF-positive RA patients (6054 ± 5842 pg/mL) than in RF-negative patients (3902 ± 2098 pg/mL), and a similar finding was also observed in anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (5810 ± 5671 pg/mL) and anti-CCP-negative (4183 ± 2187 pg/mL) RA patients. Serum ESR, RF, IgA, IgG levels and DAS28-CRP were elevated in RA patients with higher sCD27 levels than in those with lower sCD27 levels (p<0.01). Serum sCD27 might be a promising biomarker that reflects both disease activity and humoral immunity activity in RA.

Comparison of pulmonary and small airways function between idiopathic inflammatory myopathies patients with and without interstitial lung disease.

To evaluate pulmonary and small airway function in patients with idiopathic inflammatory myopathies (IIM) and make comparisons between patients with and without interstitial lung disease (ILD). Newly diagnosed IIM patients with and without ILD determined by high resolution computed tomography were included in the study. Pulmonary and small airway function was assessed by spirometry, diffusing capacity for carbon monoxide (DLCO), body plethysmography, single and multiple breath nitrogen washout, impulse oscillometry and measurement of respiratory resistance by the interrupter technique (Rint) using the Q-box system. We used discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography to evaluate for small airway dysfunction. Study cohort comprised of 26 IIM patients, 13 with and 13 without ILD. IIM-ILD patients presented more frequently with dyspnoea, fever, arthralgias and positive anti-synthetase antibodies, compared to IIM patients without ILD. Classic spirometric parameters and most lung physiology parameters assessing small airway function did not differ between the two groups. Predicted total lung capacity and residual volume (TLCN2WO, RVN2WO) measured by multiple breath nitrogen washout and the TLCN2WO/TLCpleth ratio were significantly lower in IIM-ILD patients compared to those without ILD (mean: 111.1% vs. 153.4%, p=0.034, median: 171% vs. 210%, p=0.039 and median: 1.28 vs. 1.45, p=0.039, respectively). Rint tended to be higher among IIM-ILD patients (mean:100.5% vs. 76.6%, p=0.053). Discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography in IIM-ILD patients indicate an early small airways dysfunction in these patients.

The diagnostic value of urinary N-terminal fragment of titin for skeletal muscle damage in idiopathic inflammatory myopathy.

N-terminal fragment of titin (N-titin) is a marker of sarcomere damage in striated muscles, however, its value in patients with IIM is unclear. This study aimed to investigate the diagnostic value of N-titin for skeletal muscle damage in patients with IIM. Urine samples from 62 patients with IIM, 59 patients with other CTD diseases, and 29 healthy controls were collected to detect N-titin by ELISA assays. Clinical features and laboratory data were all included in logistic regression analysis to obtain the independent predictive factor for skeletal muscle damage. Urinary N-titin level of the IIM group [168.3 (19.0, 1279.0) pmol/mg cr] was significantly higher than that in CTD controls [2.80 (1.53, 3.60)] and healthy controls [1.83 (1.09, 2.95)] (P<0.001). IIM patients with skeletal muscle injury had a significantly higher level of urinary N-titin [1001.0, (181.8, 1977.0)] than those without [9.3, (5.8, 23.9)] (P<0.001). the N-titin level was strongly correlated with CK (r = 0.907, P<0.001) and muscle disease activity assessment scores by Spearman correlation analysis. After adjusting for the anti-MDA5 antibody and cardiac troponin T, N-titin was shown to independently predict skeletal muscle damage in patients with IIM (odds ratio=1.035, 95% CI: 1.002, 1.069, P=0.039). The cut-off value of urinary N-titin to diagnose skeletal muscle damage was 89.9 pmol/mg Cr, with a sensitivity of 87.8% and a specificity of 100% (AUC=0.971, 95% CI: 0.938, 1.000, P<0.001). Urinary N-titin is a non-invasive and independent predictive factor for determining skeletal muscle damage in patients with IIM.

Incidence, features and outcome of disease relapse after COVID-19 vaccination in patients with idiopathic inflammatory myopathies.

Vaccination against coronavirus disease (COVID-19) is relatively safe in patients with idiopathic inflammatory myopathies (IIM), however, myositis flares following vaccination have been poorly studied. We aimed to evaluate the frequency, features and outcomes of disease relapses in patients with IIM following COVID-19 vaccination. A cohort of 176 IIM patients were interviewed after the 3rd wave of the COVID-19 pandemic and followed prospectively. Relapses were determined using the disease state criteria and the outcome of the flares with myositis response criteria, calculating the total improvement score (TIS). A total of 146 (82.9%) patients received a vaccination, 17/146 (11.6%) patients had a relapse within 3 months, and 13/146 (8.9%) patients within one month. The relapse rate of unvaccinated patients was 3.3%. Three months after the post-vaccination relapses, 70.6% of the patients (12/17) achieved an improvement of disease activity (average TIS score: 30±15.81; 7 minor, 5 moderate and 0 major improvements). Six months after flares improvement was detected in 15/17(88.2%) of relapsed patients (average TIS score: 43.1±19.53; 3 minimal, 8 moderate and 4 major). Forward stepwise logistic regression analysis revealed that the active state of myositis at the time of injection (p<0.0001; OR:33; CI:9-120) was significantly associated with the occurrence of a relapse. A minority of the vaccinated IIM patients had a confirmed disease flare after COVID-19 vaccination and the majority of the relapses improved after individualized treatment. An active disease state at the time of vaccination probably contributes to the increased risk of a post vaccination myositis flare. This article is protected by copyright. All rights reserved.