Antibody-positive Myositis Research Articles

Clinical features of anti-SAE1 antibody-positive myositis and interstitial lung disease: a multicenter, retrospective study in Taiwan

Clinical features of anti-SAE1 antibody-positive myositis and interstitial lung disease: a multicenter, retrospective study in Taiwan

Cardiomyopathy with anti-mitochondrial M2 antibody-positive myositis.

Cardiomyopathy with anti-mitochondrial M2 antibody-positive myositis.

Pathologic Features of Anti-Ku Myositis.

Characteristics of myositis with anti-Ku antibodies are poorly understood. The purpose of this study was to elucidate the pathologic features of myositis associated with anti-Ku antibodies, compared with immune-mediated necrotizing myopathy (IMNM) with anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, in muscle biopsy-oriented registration cohorts in Japan and Germany. We performed a retrospective pathology review of patients with anti-Ku myositis samples diagnosed in the Japanese and German cohorts. We evaluated histologic features and performed HLA phenotyping. Fifty biopsied muscle samples in the Japanese cohort and 10 in the German cohort were obtained. After exclusion of myositis-specific autoantibodies or other autoimmune connective tissue diseases, 26 samples (43%) of anti-Ku antibody-positive myositis were analyzed. All the samples shared some common features with IMNM, whereas they showed expression of MHC class II and clusters of perivascular inflammatory cells more frequently than the anti-SRP/HMGCR IMNM samples (71% vs 7%/16%; p < 0.005/<0.005; 64% vs 0%/0%; p < 0.005/<0.005). Anti-Ku myositis biopsies could be divided into 2 subgroups based on the extent of necrosis and regeneration. The group with more abundant necrosis and regeneration showed a higher frequency of MHC class II expression and perivascular inflammatory cell clusters. HLA phenotyping in the 44 available patients showed possible associations of HLA-DRB1*03:01, HLA-DRB1*11:01, and HLA-DQB1*03:01 (p = 0.0045, 0.019, and 0.027; odds ratio [OR] 50.2, 4.6, and 2.8; 95% CI 2.6-2942.1, 1.1-14.5, and 1.0-7.0) in the group with less conspicuous necrosis and regeneration. On the contrary, in the group of more abundant necrosis and regeneration, the allele frequencies of HLA-A*24:02, HLA-B*52:01, HLA-C*12:02, and HLA-DRB1*15:02 were lower than those of healthy controls (p = 0.0036, 0.027, 0.016, and 0.026; OR = 0.27, 0, 0, and 0; 95% CI 0.1-0.7, 0-0.8, 0-0.8, and 0-0.8). However, these HLA associations did not remain significant after statistical correction for multiple testing. While anti-Ku myositis shows necrotizing myopathy features, they can be distinguished from anti-SRP/HMGCR IMNM by their MHC class II expression and clusters of perivascular inflammatory cells. The HLA analyses suggest that anti-Ku myositis may have different subsets associated with myopathologic subgroups.

Inpatient Rehabilitation of a Patient with Anti-signal Recognition Antibody-positive Myositis with Persistently High Creatinine Kinase Levels at a Kaifukuki Rehabilitation Ward

Inpatient Rehabilitation of a Patient with Anti-signal Recognition Antibody-positive Myositis with Persistently High Creatinine Kinase Levels at a Kaifukuki Rehabilitation Ward

VP334 Clinicopathological features of anti-mitochondrial M2 antibody-positive myositis based on a cohort of 201 patients from Japan

VP334 Clinicopathological features of anti-mitochondrial M2 antibody-positive myositis based on a cohort of 201 patients from Japan

Magnetic resonance imaging findings of the lower limb muscles in anti-mitochondrial M2 antibody-positive myositis

Anti-mitochondrial M2 antibody (AMA-M2)-positive myositis is an idiopathic inflammatory myopathy (IIM). Of all patients with myositis, 2.5–19.5% have AMA-M2 antibodies. However, the detailed distribution of muscles affected in AMA-positive myositis is unknown. Therefore, we examined lower muscle magnetic resonance imaging (MRI) findings of patients with AMA-positive myositis. Among the 63 patients with IIM at our institute, 5 (7.9%) were positive for AMA-M2 antibodies. However, one was also positive for anti-Jo1 antibodies; therefore, four patients were finally participated in this study. All patients had high-intensity MRI signals in the proximal muscles, including the gluteus maximus and iliopsoas muscles, and in the thigh muscles, including the vastus lateralis, vastus medialis, adductor magnus, and semimembranosus muscles. Lower leg muscles were relatively spared. Fascial edema was observed in all patients and was also present in the lower leg muscles. Subcutaneous edema was observed, particularly in the proximal portion of the lower limbs. In AMA-positive myositis, proximal muscles, including the gluteus maximus, vastus lateralis, adductor magnus, and the semimembranosus, were markedly affected, while the lower leg muscles were relatively preserved. Additionally, fascial edema was evident even in lower leg muscles. Therefore, muscle MRI can be a useful diagnostic aid for AMA-positive myositis.

Differences in muscle magnetic resonance imaging findings between anti-signal recognition particle antibody-positive myopathy and anti-aminoacyl-tRNA synthetase antibody-positive myositis.

To compare the findings of muscle magnetic resonance imaging (MRI) between anti-signal recognition particle antibody-positive myopathy (anti-SRP myopathy) and anti-aminoacyl-tRNA synthetase antibody-positive myositis (anti-ARS myositis). Of the patients newly diagnosed with polymyositis (PM)/dermatomyositis (DM) and immune-mediated necrotising myopathy (IMNM) admitted to our Department between April 2012 and December 2021, those who met the eligibility criteria of positive for anti-SRP or anti-ARS antibodies and thigh MRI at the time of diagnosis were included. We compared the lesion sites and MRI findings of the thigh muscles that were classified into oedema, fascial oedema, fatty replacement, and muscle atrophy between the three groups of anti-SRP myopathy, anti-Jo-1 antibody-positive myositis, and non-Jo-1 antibody-positive myositis. Of the 98 PM/DM and IMNM patients, five anti-SRP myopathy patients and 11 anti-Jo-1-positive and 22 non-Jo-1 antibody-positive patients with myositis were included. The SRP group showed significantly higher blood levels of myogenic enzymes such as serum creatinine kinase (CK) than the other groups (p=0.01). In thigh MRI findings, despite oedema in most cases in anti-SRP and anti-ARS groups, fascial oedema was identified only in the ARS group, frequently in Jo-1 positive patients in particular. Moreover, gluteus maximus muscle lesions occurred more frequently in the SRP group than in the ARS group (p=0.008). A comparison of thigh MRI between anti-SRP myopathy and anti-ARS myositis showed different findings and lesion sites reflecting the different pathophysiology that may contribute to their diagnosis.

VP.45 Clinical features of anti-mitochondrial M2 antibody-positive myositis: Case series of 17 patients

To clarify the prevalence, clinical features, treatment outcome, and severity determinants of anti-mitochondrial M2 antibody-positive myositis (AMA-M2-positive myositis). Clinical data for AMA-M2-positive myositis patients who were treated at Hokkaido University Hospital and other participating facilities from 2012 to 2021 were retrospectively evaluated. Of a total 182 patients with inflammatory myositis, 17 patients (13 females and 4 males) were AMA-M2-positive (mean age, 57.4 years; SD, 9.4 years). The median duration before diagnosis was 24 months (interquartile range [IQR]: 12-85), indicating a trend of delayed diagnosis of this disease. Weakness mainly involving paravertebral muscles, weight loss, respiratory failure, and cardiac complications were typical symptoms, but the course and severity of each symptom varied from case to case. Twelve patients (71%) had vital capacity percentage (%VC) of less than 80% and 4 patients needed ventilator support. The average body mass index (BMI) at diagnosis was 19.6 (SD, 4.1). Thirteen patients (76%) had cardiac complications and 6 patients showed lower left ventricular ejection fraction (LVEF) less than 50%. A strong correlation was found between %VC and mRS scores (R=0.68, p=0.002), indicating a trend for the degree of respiratory dysfunction to be linked to a decline in ADL. The correlation between %VC and BMI was also strong (R=0.68, p=0.002), indicating that weight loss can be an indicator of potential progression of respiratory failure. Fourteen patients received immunotherapy and CK level improved within a few months. %VC and mRS scores also improved significantly. We found significant correlations of %VC with BMI and mRS scores in AMA-M2-positive myositis patients. Immunotherapy improved the CK level, respiratory dysfunction, and ADL. We propose that CK level, %VC and BMI should be monitored as disease indicators in treatment of AMA-M2-positive myositis.

The effect of immunosuppressive therapy on cardiac involvements in anti-mitochondrial antibody-positive myositis.

Anti-mitochondrial antibody (AMA)-positive myositis is frequently associated with various cardiac involvements, such as arrhythmia and left ventricular (LV) dysfunction. However, the efficacy of immunosuppressive therapy in these complications remains unknown. This study aimed to investigate the cardiac response to immunosuppressive therapy in patients with AMA-positive myositis. The clinical data of 15 AMA-positive myositis patients with cardiac involvement were retrospectively collected at our centre. To evaluate the effects of immunosuppressive therapy, echocardiographic and laboratory data of patients who received glucocorticoid therapy with additional immunosuppressants (n=6) and those who did not (n=6) were compared. Also, the characteristics of patients with or without >5% LV ejection fraction (LVEF) decline during the follow-up period (n=5 vs. n=7) were compared. Thirteen patients (87%) had arrhythmias, and eight patients (53%) had LV wall motion abnormalities. Although arrhythmias decreased after treatment, reduced LVEF and LV wall motion abnormalities persisted. Further investigation revealed an increased LV end-systolic dimension and reduced LVEF in patients without additional immunosuppressive therapy, while those in patients with additional immunosuppressive therapy were maintained. Six of seven patients (86%) without LVEF decline received additional immunosuppressive therapy, whereas no patients with LVEF decline had additional immunosuppressive therapy. Cardiac involvement in AMA-positive myositis may worsen even with glucocorticoid monotherapy, and there might be some associations between the change of LV function and additional immunosuppressive therapy.

Clinical features of anti-mitochondrial M2 antibody-positive myositis: case series of 17 patients

ObjectiveIn 2012, a large number of myositis cases with anti-mitochondrial M2 (AMA-M2) antibody, which had well been known as the serological hallmark for primary biliary cholangitis (PBC), were reported in Japan. Recently, some case series from Japan, France, America, China and India have shown that approximately 2.5% to 19.5% of patients with myositis have AMA-M2 antibody. The objective of this study was to clarify the prevalence, clinical features, treatment outcome, and severity determinants of AMA-M2 positive myositis. MethodsThis study was a multicenter observational study. We enrolled patients who were diagnosed with myositis during a ten-year period between 2012 and 2021. ResultsOf the total of 185 patients with inflammatory myopathy, 17 patients were positive for AMA-M2 antibody. The typical symptoms were weakness mainly involving paravertebral muscles, weight loss, respiratory failure, and cardiac complications. Thirteen of the 17 patients had cardiac complications. A strong correlation was found between respiratory failure and modified Rankin Scale (mRS) score. A strong correlation was also found between respiratory failure and body weight, indicating that weight loss can be an indicator of potential progression of respiratory failure. Six of the 17 patients were complicated by malignancy. ConclusionsThis study showed significant correlations between % vital capacity (VC), body mass index (BMI), and mRS score in patients with AMA-M2-positive myositis. Immunotherapy often improved CK level and respiratory dysfunction. We therefore propose that %VC and BMI should be monitored as disease indicators in treatment of AMA-M2-positive myositis.

Clinical Heterogeneity of Patients With Antinuclear Matrix Protein 2 Antibody-Positive Myositis: A Retrospective Cohort Study in China.

Heterogeneity exists among patients with myositis who have antinuclear matrix protein 2 (anti-NXP2) antibodies, although they usually present with severe muscle weakness. This study aimed to investigate the differences in phenotypes and prognoses among adult patients with myositis who have anti-NXP2 antibodies. Adult patients with myositis who have anti-NXP2 antibodies were enrolled from January 2010 to December 2019. Their clinical features and laboratory data were recorded retrospectively. We followed up on their survival status until June 30, 2020. A hierarchical cluster analysis, Kaplan-Meier curves, and classification and regression trees were used to analyze the data. A total of 70 adult patients with myositis who have anti-NXP2 antibodies were enrolled. All patients experienced muscle weakness. A total of 11 patients did not present with rashes during disease progression, and 43 patients developed dysphagia. In total, 21 patients had interstitial lung disease (ILD), whereas no patients had rapidly progressive ILD. Hierarchical cluster analysis identified 2 clusters. Patients in cluster 1 were younger at disease onset, had a higher incidence of subcutaneous calcification, and had a lower incidence of V sign and shawl sign. Patients in cluster 2 had a higher frequency of ILD, accompanied by lower levels of lymphocytes and higher levels of serum ferritin. Moreover, patients in cluster 2 had worse prognoses. Patients with myositis who have anti-NXP2 antibodies may present with different phenotypes that are characterized by unique features and prognoses.

Anti-mitochondrial M2 antibody-positive myositis mimicking amyotrophic lateral sclerosis (2018)

Anti-mitochondrial M2 antibody-positive myositis mimicking amyotrophic lateral sclerosis (2018)

78. Atypical presentation of anti-signal recognition particle antibody positive myositis with profound extra-muscular features

78. Atypical presentation of anti-signal recognition particle antibody positive myositis with profound extra-muscular features

A case of non-ischemic heart failure associated with anti-mitochondrial antibody-positive myositis

A case of non-ischemic heart failure associated with anti-mitochondrial antibody-positive myositis

Anti-Mi-2 antibody positive myositis: Clinical and histopathological features in three patients

Background: Anti-Mi-2 antibody have been detected dominantly in patients with dermatomyositis and characterized by typical cutaneous lesions, mild muscle weakness, and well-response to corticosteroid treatment.

Clinical features of anti-mitochondrial antibody positive myositis

Clinical features of anti-mitochondrial antibody positive myositis

Cardiac Involvements in Anti-Mitochondrial Antibody-Positive Myositis (P07.046)

Cardiac Involvements in Anti-Mitochondrial Antibody-Positive Myositis (P07.046)

Characterization and peripheral blood biomarker assessment of anti–Jo‐1 antibody–positive interstitial lung disease

Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti-Jo-1 antibodies. A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti-Jo-1 antibody-positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti-Jo-1 antibody-positive ILD. Among the 90 anti-Jo-1 antibody-positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti-Jo-1 antibody-positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti-signal recognition particle antibody-positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. In this large cohort of anti-Jo-1 antibody-positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti-Jo-1 antibody-positive ILD and serum levels of CRP as well as the interferon-gamma-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.