Juvenile dermatomyositis with Anti-SAE antibodies in a Moroccan child associated with pseudo-angioedema: a case report.

BACKGROUND: Juvenile Dermatomyositis (JDM) is the leading cause of non-infectious inflammatory myopathy in children. It is a heterogeneous group of autoimmune diseases characterized by a variable combination of muscular, dermatological, and visceral involvement. Myositis-specific autoantibodies help define homogeneous subgroups with common clinical characteristics and prognoses. Anti-SAE (small ubiquitin-like modifier 1 (SUMO-1) activating enzyme) antibodies are among the most recently discovered specific autoantibodies. The presence of these antibodies is very rare, making it challenging to define clinical features and prognosis in the juvenile form. We report the first case of an African patient with juvenile dermatomyositis and positive anti-SAE antibodies. CASE REPORT: A 5-year-3-month-old Moroccan boy presented to the pediatric emergency department with dysphagia that had been evolving for two days, preceded two months earlier by facial erythema associated with fatigue, lower limb pain, difficulty walking, and progressive inflammatory polyarthralgia. On admission, the child had a heliotrope rash with predominant pseudo-angioedema on the lips, periungual telangiectasia, and Gottron's papules over the bilateral interphalangeal and metatarsophalangeal joints. The patient had a more pronounced proximal muscle weakness in the lower limbs. He had no urticaria, fever, arthritis, calcinosis, cutaneous ulcers, or lipodystrophy. The Joint examination was normal, as was the pleuropulmonary examination. The electroneuromyography showed myogenic changes in all four limbs. Laboratory findings showed elevated levels of creatine phosphokinase and lactate dehydrogenase and a mild inflammatory syndrome. The electrocardiogram was normal. The anti-SAE antibodies were positive. The boy was diagnosed with juvenile dermatomyositis. He received methylprednisolone bolus therapy followed by oral prednisone. The latter was gradually tapered in combination with weekly intramuscular methotrexate. As a result, dysphagia disappeared within 48 h. After two weeks, there was an improvement in the muscular score and a significant regression of facial pseudo-angioedema. CONCLUSION: We report the first African patient with anti-SAE autoantibody-positive JDM. He had a typical dermatological manifestation of JDM associated with pseudo-angioedema predominant on the lips; a rarely reported sign in DM and JDM patients. The patient responded well to corticosteroid therapy and methotrexate.

Murine models of idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are divided into polymyositis and dermatomyositis (DM) with specific cutaneous manifestation. Several myositis-specific autoantibodies (MSAs) have been identified in IIMs and were found to be associated with distinct clinical features, including anti-synthetase syndrome (ASyS) and immune-mediated necrotizing myopathy (IMNM). Moreover, MSA-related clinical features have been identified even within DM. Although MSAs are valuable for the diagnosis of IIMs, the pathogenic roles of these antibodies remain unknown. To investigate the pathogenesis of IIMs, classical murine models of autoimmune myositis, experimental autoimmune myositis, and C protein-induced myositis have been established by immunization with muscle-specific antigens, myosin, and myosin-binding skeletal C protein, respectively. To according to MSA-related autoimmunity, a murine model of ASyS was generated by immunization with a murine recombinant histidyl-transfer RNA (tRNA) synthetase, Jo-1, in which muscle and lung inflammation are induced depending on acquired immunity. Furthermore, it was found that the transfer of human Immunoglobulin G (IgGs) from patients with IMNM, comprising anti-signal recognition particles and anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies, induced complement-mediated myositis in recipient mice. We found that CD8+ T cell-mediated myositis can be established depending on autoimmunity against transcriptional intermediary factor 1γ (TIF1γ), an autoantigen for MSAs induced by recombinant human TIF1γ immunization. These new murine models reflecting MSA-associated IIMs will reveal the immunological mechanisms underlying IIMs.

Immune cell profiles of idiopathic inflammatory myopathy patients expressed anti-aminoacyl tRNA synthetase or anti-melanoma differentiation-associated gene 5 autoantibodies.

BACKGROUND: Patients with idiopathic inflammatory myopathy (IIM) often express a different type of myositis-specific autoantibodies (MSAs), each associated with different clinical symptoms. Understanding the immunopathogenesis of various IIM subgroups can help improve the diagnosis and prognosis of IIM patients with different MSAs. However, the immune cell profiles of these IIM patients with anti-aminoacyl tRNA synthetase (ARS) or anti-melanoma differentiation-associated gene 5 (MDA5) autoantibodies remain unclear. We focused on the immune cell profiles of IIM patients with anti-ARS or anti-MDA5 autoantibodies. RESULTS: The peripheral blood from IIM patients with anti-MDA5 autoantibody (MDA5 + group, n = 24) or one of the anti-ARS autoantibodies (ARS + group, n = 40) autoantibodies, and healthy controls (HC group, n = 60) were collected and examined. We found that IIM patients had a lower CD3 T cell population compared to the HC group. IIM patients showed a significantly lower TN cell population and a higher TEMRA cell population. Higher Th17 and Treg cell populations were found in these IIM patients than in the HC group. In these IIM patients, the MDA5 + group exhibited the higher percentages of Th17 and Treg cells than the ARS + group. It is noteworthy that the percentage of Th1 cells in the survival subgroup was higher than in the death subgroup in IIM patients with ARS + or MDA5 + . Furthermore, in the MDA5 + group, the percentage of Treg cells was higher in the survival subgroup compared to the death subgroup. CONCLUSIONS: Our study demonstrated that elevated Th1 may be a good prognostic indicator in IIM patients with ARS + or MDA5 + . Elevated Treg may also help predict a good prognosis in MDA5 + IIM patients. However, more large-scale studies and clinical samples are needed to verify the significance of Th1 and Treg cell subsets in clinical outcomes for these IIM patients with ARS + or MDA5 + . These data may help design a therapeutic approach that specifically targets the pathogenic immune molecular responsible for autoimmune attacks in IIM.

Association between self-reported race and ethnicity and myositis-specific autoantibodies in a diverse cohort of patients with inflammatory myopathy.

Myositis-specific autoantibodies (MSAs) are highly specific biomarkers for idiopathic inflammatory myopathies (IIMs). We investigated whether self-reported race and ethnicity were associated with the presence of specific MSAs. Charts of patients with IIM seen at 3 large healthcare systems in the same US city were reviewed. Demographic data and MSA test results were abstracted. Associations between race and ethnicity and presence of MSAs were analyzed using bivariate analysis and further characterized using separate unadjusted and adjusted logistic regression models. One hundred twenty-one subjects were included (19% Asian, 10% Black or African American, 27% Latinx or Hispanic, 36% non-Hispanic White, and 7% Other). In a bivariate analysis, anti-Jo-1 and anti-MDA5 autoantibodies were associated with race and ethnicity (p = 0.03 and 0.02, respectively). Black or African American subjects had increased odds of a positive anti-Jo-1 result compared to non-Hispanic White subjects on unadjusted logistic regression analysis (OR 8.61, 95% CI 1.61-46.07), although after adjustment for age and gender this finding was not significant. Subjects categorized as Other had increased odds of a positive anti-MDA5 result compared to non-Hispanic White subjects on both unadjusted (OR 55.0, 95% CI 2.02-1493) and adjusted analyses (OR 44.8, 95% CI 1.55-1298). Anti-Jo-1 and anti-MDA5 autoantibodies were significantly associated with race and ethnicity on bivariate analysis. Black or African American subjects had increased odds of positive anti-Jo-1 autoantibody on unadjusted, but not adjusted, logistic regression analysis. Subjects characterized as Other had increased odds of positive anti-MDA5 autoantibody, although confidence intervals were wide. Key Points • Association found between MSAs and race and ethnicity in diverse US cohort • Anti-Jo-1 and anti-MDA5 associated with race and ethnicity in bivariate analyses.

Serum metabolomic analysis reveals disorder of steroid hormone biosynthesis in patients with idiopathic inflammatory myopathy.

Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of autoimmune diseases with various clinical manifestations, treatment responses, and prognoses. According to the clinical manifestations and presence of different myositis-specific autoantibodies (MSAs), IIM is classified into several major subgroups, including PM, DM, IBM, ASS, IMNM, and CADM. However, the pathogenic mechanisms of these subgroups remain unclear and need to be investigated. Here, we applied MALDI-TOF-MS to examine the serum metabolome of 144 patients with IIM and analyze differentially expressed metabolites among IIM subgroups or MSA groups. The results showed that the DM subgroup had lower activation of the steroid hormone biosynthesis pathway, while the non-MDA5 MSA group had higher activation of the arachidonic acid metabolism pathway. Our study may provide some insights into the heterogeneous mechanisms of IIM subgroups, potential biomarkers, and management of IIM.

New paradigm in the treatment of myositis-associated interstitial lung disease.

INTRODUCTION: Interstitial lung disease (ILD) is the leading cause of mortality in idiopathic inflammatory myopathies or myositis. Clinical characteristics, including the course of ILD, rate of progression, radiological and pathohistological morphologies, extent and distribution of inflammation and fibrosis, responses to treatment, recurrence rate, and prognosis, are highly variable among myositis patients. A standard practice for ILD management in myositis patients has not yet been established. AREAS COVERED: Recent studies have demonstrated the stratification of patients with myositis-associated ILD into more homogeneous groups based on the disease behavior and myositis-specific autoantibody (MSA) profile, leading to better prognoses and prevention of the burden of organ damage. This review introduces a new paradigm in the management of myositis-associated ILD based on research findings from relevant literature selected by a search of PubMed as of January 2023, as well as expert opinions. EXPERT OPINION: Managing strategies for myositis-associated ILD are being established to stratify patients based on the severity of ILD and the prediction of prognosis based on the disease behavior and MSA profile. The development of a precision medicine treatment approach will provide benefits to all relevant communities.

Performance of cut-offs adjusted with positive control band intensity in line-blot assays for myositis-specific antibodies.

The diagnostic performance of band intensity (BI) cut-offs, adjusted by a positive control band (PCB) in a line-blot assay (LBA) for myositis-related autoantibodies (MRAs) is investigated. Sera from 153 idiopathic inflammatory myositis (IIM) patients with available immunoprecipitation assay (IPA) data and 79 healthy controls were tested using the EUROLINE panel. Strips were evaluated for BI using the EUROLineScan software, and the coefficient of variation (CV) was calculated. Sensitivity and specificity, area under the curve (AUC), and the Youden's index (YI) were estimated at non-adjusted or PCB-adjusted cut-off values. Kappa statistics were calculated for IPA and LBA. Although inter-assay CV for PCB BI was 3.9%, CV was 12.9% in all samples, and a significant correlation was found between BIs of PCB and seven MRAs (all P < 0.05). At adjusted BI (aBI) > 10, the negative conversion rate of myositis-specific autoantibody (MSA)-positivity at BI > 10 was 11.5% in controls and 1.3% in patients. The specificity, AUC, and YI for MSAs at aBI > 10 or > 20 were higher than those at non-adjusted cut-off values. Additionally, AUC (0.720), YI (0.440), and the prevalence of MRAs with kappa > 0.60 (58.3%) were the highest at aBI > 20. The overall sensitivity and specificity for MSAs were 50.3% and 93.7% at aBI > 20, respectively, and 59.5% and 65.8% with BI > 10, respectively. The diagnostic performance of LBA can be improved using PCB-adjusted BIs. aBI > 20 is the optimal cut-off for IIM diagnosis using the EUROLINE LBA panel.

Leflunomide-Induced Immune-Mediated Necrotizing Myopathy in a Patient With Rheumatoid Arthritis: A Case Report.

Immune-mediated necrotizing myopathy (IMNM) is a subtype of inflammatory myopathy that is characterized by proximal muscle weakness, markedly elevated serum creatine kinase, myopathic electromyographic findings, and muscle biopsies revealing necrosis or regeneration with sparse inflammatory infiltrate. IMNM tends to be idiopathic but has been associated with certain medications. This supports the possibility for other pharmacotherapies to induce IMNM-particularly leflunomide. Leflunomide is used in the treatment for rheumatoid arthritis and has been shown to induce autoimmune diseases-including autoimmune hepatitis and polymyositis. After an extensive review of history and workup of muscle weakness, we conclude that leflunomide induced an IMNM in our patient. As this is the first case of leflunomide-induced IMNM, it is important for clinicians to suspect an inflammatory myopathy in the setting of myositis while on leflunomide.

Murine models of idiopathic inflammatory myopathy.

Idiopathic inflammatory myopathies (IIMs) are characterized by inflammation of muscles and other organs. Several myositis-specific autoantibodies (MSAs) have been identified in IIMs and were found to be associated with distinct clinical features. Although MSAs are valuable for the diagnosis of IIMs, the pathogenic roles of these antibodies remain unknown. To investigate the pathogenesis of IIMs, several animal models of experimental myositis have been established. Classical murine models of autoimmune myositis, experimental autoimmune myositis, and C protein-induced myositis are established by immunization with muscle-specific antigens, myosin, and skeletal C protein, respectively. Furthermore, a murine model of experimental myositis was generated by immunization with a murine recombinant histidyl-tRNA synthetase, Jo-1, in which muscle and lung inflammation reflecting anti-synthetase syndrome are induced depending on acquired immunity. Recently, the transfer of human IgGs from patients with immune-mediated necrotizing myopathy, comprising anti-signal recognition particles and anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies, was found to induce complement-mediated myositis in recipient mice. CD8+ T cell-mediated myositis can be established depending on autoimmunity against transcriptional intermediary factor 1γ (TIF1γ), an autoantigen for MSAs induced by recombinant human TIF1γ immunization. These new murine models reflecting MSA-related IIMs are useful tools for accurately understanding the pathological mechanisms underlying IIMs.

The clinical features and prognoses of anti-MDA5 and anti-aminoacyl-tRNA synthetase antibody double-positive dermatomyositis patients.

Objective: To explore the clinical features and prognoses of dermatomyositis (DM) associated with a double-positive anti-MDA5 and anti-aminoacyl-tRNA synthetase (anti-ARS) antibody presentation. Methods: We retrospectively analyzed 1280 consecutive patients with idiopathic inflammatory myopathy (IIM). Individuals with anti-MDA5 and anti-ARS antibodies (anti-MDA5+/ARS+) were compared to anti-MDA5-/ARS+ and anti-MDA5+/ARS- control individuals based on clinical, pulmonary radiological characteristics, treatment, and follow-up information. Results: Six individuals (0.47%) presented with anti-MDA5+/ARS+; of these, 2 (33.3%) were anti-PL-12+, 2 (33.3%) were anti-Jo-1+, 1 (16.7%) was anti-EJ+, and 1 (16.7%) was anti-PL-7+. Hallmark cutaneous manifestations, including Gottron's sign (100%), heliotrope rash (50%), mechanic's hand (66.7%), and skin ulcers (16.7%) were common. Anti-MDA5+/ARS+ patients tended to have higher ferritin levels (p = 0.038) than anti-MDA5-/ARS+ group, and higher CD4+ T-cell counts (p = 0.032) compared to the anti-MDA5+/ARS- group. Radiologically, NSIP with OP overlap was predominant (60%). Consolidation (60%), ground-glass attenuation (GGA) (80%), traction bronchiectasis (80%), and intralobular reticulation (100%) were common in anti-MDA5+/ARS+ individuals. All were diagnosed with ILD and 50% were categorized as RPILD. All patients received glucocorticoids combined with one or more immunosuppressants. Most (83.3%) had a good prognosis following treatment, but there was no difference in the survival rate between the three subgroups. Conclusion: Presentation with anti-MDA5+/ARS+ DM was rare. The clinical and radiological characteristics of anti-MDA5+/ARS+ DM combined the features of anti-MDA5+ and anti-ARS+ individuals. Individuals with anti-MDA5+/ARS+ antibodies may respond well to glucocorticoid therapy; glucocorticoids combined with one or more immunosuppressants may be considered a basic treatment approach.

Interstitial Lung Disease in Dermatomyositis Without Myositis-Specific and Myositis-Associated Autoantibodies: Study of a Series of 72 Patients From a Single Cohort.

Objective: The clinical features of interstitial lung disease (ILD) in patients with dermatomyositis (DM) and negative myositis autoantibodies had not been exactly demonstrated previously. This study aimed to describe and expand the phenotype of interstitial lung disease (ILD) in this cohort of patients. Methods: A total of 1125 consecutive Chinese patients with idiopathic inflammatory myopathies (IIM) between 2006 and 2020 were screened retrospectively. All proven cases of isolated ILD with both negative myositis-specific autoantibodies (MSA) and negative myositis-associated autoantibodies (MAA) were selected for inclusion. The clinical features and outcome among this group, MDA5+DM (DM patients with positive anti-MDA5 antibody) and ASS (patients with positive anti-aminoacyl tRNA synthetases antibodies were recorded and compared. Results: Of 1125 IIM patients with an average follow-up of 6 years, 154 DM patients with negative MSA and MAA (MSA/MAA) were identified, with an ILD incidence of 46.8%. DM-ILD Patients with negative MSA/MAA presented younger age at onset (p<0.001), lower incidence of elevated CA153 (p=0.03) and fever (p=0.04)than those ILD patients with MDA5+DM and ASS.The estimated high-resolution computed tomography patterns of ILD showed non-specific interstitial pneumonia (66.6%), followed by organizing pneumonia in patients with negative MSA/MAA. OP pattern was more common in patients with MDA5+DM (69.7%), and the ratios of the OP (48.7%) and NSIP (51.3%) patterns were almost equal in patients with ASS. Of these DM-ILD patients with negative MSA/MAA, 25% developed rapidly progressive interstitial lung disease (RP-ILD). Patients with RP-ILD had a shorter disease duration (p=0.002), higher percentage of positive ANA(p=0.01) and organizing pneumonia patterns (p=0.04), elevated CYFRA211(p=0.04) and decreased FiO2/PaO2 (p<0.001) than those with chronic progressive ILD. The incidence of OP pattern in RP-ILD patients with negative MSA/MAA was lower than in those RPILD patients with MDA5+ DM (75%) and ASS (89%) (p=0.006). The cumulative 5- and 10-year survival rates in the DM-ILD patients with negative MSA/MAA were 91% and 88%, respectively, during the long-term follow-up study. And they had more favorable survival rate compared with ILD patients with MDA5+DM and ASS (p<0.001). An independent prognostic factor was identified as decreased PaO2/FiO2 (hazard ratio, 0.97; p=0.004]. Conclusions: This study indicates DM-ILD patients with negative MSA/MAA had favorable long-term outcomes. Decreased baseline PaO2/FiO2 acted as an independent prognostic factor for this group of patients.

Management of Myositis-Associated Interstitial Lung Disease.

Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases characterized by muscular involvement and extramuscular manifestations. Interstitial lung disease (ILD) has major pulmonary involvement and is associated with increased mortality in PM/DM/CADM. The management of PM-/DM-/CADM-associated ILD (PM/DM/CADM-ILD) requires careful evaluation of the disease severity and clinical subtype, including the ILD forms (acute/subacute or chronic), because of the substantial heterogeneity of their clinical courses. Recent studies have highlighted the importance of myositis-specific autoantibodies' status, especially anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl tRNA synthetase (ARS) antibodies, in order to evaluate the clinical phenotypes and treatment of choice for PM/DM/CADM-ILD. Because the presence of the anti-MDA5 antibody is a strong predictor of a worse prognosis, combination treatment with glucocorticoids (GCs) and calcineurin inhibitors (CNIs; tacrolimus (TAC) or cyclosporin A (CsA)) is recommended for patients with anti-MDA5 antibody-positive DM/CADM-ILD. Rapidly progressive DM/CADM-ILD with the anti-MDA5 antibody is the most intractable condition, which requires immediate combined immunosuppressive therapy with GCs, CNIs, and intravenous cyclophosphamide. Additional salvage therapies (rituximab, tofacitinib, and plasma exchange) should be considered for patients with refractory ILD. Patients with anti-ARS antibody-positive ILD respond better to GC treatment, but with frequent recurrence; thus, GCs plus immunosuppressants (TAC, CsA, azathioprine, and mycophenolate mofetil) are often needed in order to achieve favorable long-term disease control. PM/DM/CADM-ILD management is still a therapeutic challenge for clinicians, as evidence-based guidelines do not exist to help with management decisions. A few prospective clinical trials have been recently reported regarding the treatment of PM/DM/CADM-ILD. Here, the current knowledge on the pharmacologic managements of PM/DM/CADM-ILD was mainly reviewed.

Comparison of the 2017 EULAR/ACR Criteria with Clinicoserologic Criteria for the Classification of Idiopathic Inflammatory Myopathies in Korean Patients.

PURPOSE: To investigate correlations between myositis-specific autoantibodies (MSA) or myositis-associated antibodies (MAA) and clinical features, thereby demonstrating the utility of clinicoserologic classification in idiopathic inflammatory myopathies (IIM) patients. MATERIALS AND METHODS: We conducted a multicenter study of 108 adult patients (age ≥18 years) who were diagnosed with IIM by Peter and Bohan criteria or 2004 European Neuromuscular Centre (ENMC) criteria. Clinical data were obtained by medical record review. Immunoblot assay with Euroline strip (EUROIMMUN, Germany) was performed using the sera of dermatomyositis (DM, n=56), polymyositis (PM, n=45), amyopathic DM (n=5), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (n=1) patients. Patients were classified based on two classifications: 2017 EULAR/ACR and novel clinicoserologic classification. RESULTS: According to 2017 EULAR/ACR criteria, DM and PM were the most and the second most frequent entities. Overlap myositis was the major entity of IIM, and the frequency of PM was significantly lower when applying clinicoserologic classification criteria. Sixty-nine (63.9%) patients had one or more MSA, and 61 (56.5%) patients had one or more MAA. Interstitial lung disease was closely associated with anti-MDA5 and anti-ARS, and DM-specific skin lesions were frequently observed in patients with anti-TIF1γ, anti-SRP, and anti-MDA5. CONCLUSION: The clinicoserologic criteria based on MSA/MAA positivity could reflect more precise clinical features of IIM. Establishment of a laboratory system routinely available to screen for MSA/MAA status will be beneficial to provide precise diagnosis and proper management of IIM patients.

Anti-SAE autoantibody-positive Japanese patient with juvenile dermatomyositis complicated with interstitial lung disease - a case report.

BACKGROUND: Clinical phenotypes and outcomes in juvenile dermatomyositis (JDM) have been defined by various myositis-specific autoantibodies (MSAs). One of the recently described MSAs associated with DM is targeted against the small ubiquitin-like modifier 1 activating enzyme (SAE). We report an anti-SAE autoantibody-positive JDM patient complicated with interstitial lung disease (ILD). CASE PRESENTATION: An 8-year-8-month-old Japanese girl presented with bilateral eyelid edema and facial erythema. At 8 years 4 months, she had dry cough and papules with erythema on the dorsal side of the interphalangeal joints of both hands. Her facial erythema gradually worsened and did not improve with topical steroids. At the first visit to our department at 8 years 8 months of age, she had a typical heliotrope rash and Gottron's papules, with no fever or weight loss, and a chest computed tomography scan showed ground-glass opacity under visceral pleura. There was no clinical evidence of myositis, muscle weakness, myalgia, or muscle magnetic resonance imaging (MRI) findings. She had mild dry cough, without any signs of respiratory distress. Laboratory tests showed no elevated inflammatory markers. She had a normal serum creatine kinase level with a slightly elevated aldolase level, and serum anti-SAE autoantibody was detected by immunoprecipitation-western blotting. She was diagnosed with juvenile amyopathic DM complicated by ILD and received two courses of methylprednisolone pulse therapy followed by oral corticosteroid and cyclosporin A. We gradually reduced the corticosteroid dose as her skin rash improved after treatment initiation. There was no progression of muscle symptoms, dysphagia, or disease flare during a 24-month follow-up period. CONCLUSIONS: We report a patient with anti-SAE autoantibody-positive JDM complicated by interstitial pneumonia. This patient had no progression of muscle symptoms and dysphagia during a 24-month follow-up period, which differs from previous reports in adult patients with MSAs. There have been no previous reports of pediatric patients with SAE presenting with ILD. However, ILD seen in this case was not rapidly progressive and did not require cytotoxic agents. To prevent overtreatment, appropriate treatment choices are required considering the type of ILD.

A Case of Dermatomyositis Coexisting with Both Anti-Mi-2 and Anti-NXP-2 Antibodies.

Myositis-specific autoantibodies (MSAs) including anti-Mi-2 and anti-nuclear matrix protein 2 (NXP-2) antibodies have been detected in the patients with dermatomyositis (DM), and are useful tools for identifying clinical subsets of DM. MSAs are exclusively found in DM patients. Anti-Mi-2 antibody-positive DM patients show the typical skin lesions and myositis and are rarely associated with internal malignancy and interstitial lung disease (ILD). On the other hand, adult DM patients with anti-NXP-2 antibody often show calcinosis and internal malignancy, but rarely ILD. In addition, anti-NXP-2 antibody-positive DM patients have severe phenotype with myalgia, peripheral edema, and significant dysphagia, but with mild skin lesions. Herein, we report a rare case of classic DM coexisting with both anti-Mi-2 and anti-NXP-2 antibodies, clinically, without ILD or internal malignancy. Our patient had typical skin manifestations, muscle weakness, muscle pain, and general fatigue without calcinosis, peripheral edema, or dysphagia. Thus, the clinical phenotype was similar to anti-Mi-2 antibody-positive DM.

The spectrum and clinical significance of myositis-specific autoantibodies in Chinese patients with idiopathic inflammatory myopathies.

OBJECTIVES: The aim of this study is to analyze the prevalence of myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with polymyositis (PM) and dermatomyositis (DM). METHODS: Twelve subsets of MSAs including anti-Mi-2, anti-TIF1-γ, anti-MDA5, anti-NXP2, anti-SAE1, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, anti-OJ, and anti-HMGCR antibodies were tested. Four hundred and ninety-seven PM/DM patients were enrolled. Clinical features and laboratory data were collected. The frequency of MSAs and the correlations with clinical phenotypes were calculated by SPSS 21.0. RESULTS: MSAs were present in 65.4% in PM/DM patients. Anti-TIF1-γ (14.3%), anti-MDA5 (12.5%), and anti-Jo-1 (10.1%) were the three commonest MSAs. Anti-SAE1 (OR 14.877, 95% CI 1.427-155.074), anti-SRP (OR 4.339, 95% CI 1.529-12.312) and anti-TIF1-γ (OR 2.790, 95% CI 1.578-4.935) were associated with dysphagia. In contrast, anti-MDA5 (OR 0.356, 95% CI 0.148-0.856) might decrease the frequency of this manifestation. Interstitial lung disease (ILD) was observed more frequently in patients carrying anti-EJ (OR 14.202, 95% CI 1.696-118.902), anti-Jo-1 (OR 11.111, 95% CI 3.306-37.335), and anti-MDA5 (OR 3.109, 95% CI 1.578-6.128). On the contrary, anti-Mi-2 (OR 0.180, 95% CI 0.055-0.589), anti-TIF1-γ (OR 0.163, 95% CI 0.080-0.333), and anti-HMGCR (OR 0.058, 95% CI 0.007-0.451) were protective factors against developing ILD. Anti-TIF1-γ was an independent risk factor for cancer-associated myositis (OR 4.237, 95% CI 1.712-10.487). CONCLUSIONS: PM/DM patients had high frequencies of MSAs. Several MSAs were independent factors in determining unique clinical phenotypes.

Myositis-specific autoantibodies in Japanese patients with juvenile idiopathic inflammatory myopathies.

OBJECTIVES: The aim of our study is to clarify the association of myositis-specific autoantibodies (MSAs) with clinical and laboratory features in Japanese patients with juvenile idiopathic inflammatory myopathies (JIIMs). METHODS: We retrospectively analyzed the frequency of MSAs and their association with clinical or laboratory findings in 25 Japanese patients with JIIMs in Hokkaido district. RESULTS: Eighteen of the 25 patients (72%) were positive for MSAs; seven with anti-melanoma differentiation associated gene (MDA) 5 (28%), five with anti-transcriptional intermediary factor (TIF)-1γ (20%), four with anti-MJ/nuclear matrix protein (NXP)-2 (16%), two with anti-Jo-1 (8%), one with anti- HMG-CoA reductase, one with anti-signal recognition peptide (SRP) antibodies (4% each), including co-existence and transition of MSAs in one patient each. Anti-MDA5 antibodies were related to interstitial lung disease (ILD) and arthritis but not to amyopathic juvenile dermatomyositis. Drug-free remission was achieved, once ILD was overcome in this group. Anti-TIF-1γ antibodies were associated with typical rashes and mild myositis. Anti-MJ/NXP2 and anti-SRP antibodies were associated with severe muscle weakness. No patient was complicated with malignancy. CONCLUSION: Anti-MDA5 antibodies are prevalent and closely associated with ILD in our series compared with other countries. There was no apparent difference in clinical features associated with other MSAs among races.

Expression of myxovirus-resistance protein A: a possible marker of muscle disease activity and autoantibody specificities in juvenile dermatomyositis.

AIMS: To evaluate the relationship between expression of myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in juvenile dermatomyositis (JDM) patients. Also, another aim was to investigate whether the expression of MxA is related with myositis-specific autoantibodies (MSA) status in JDM patients. METHODS: 103 patients (median aged 6.3, interquartile range 0.5-15.9) enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS). Muscle biopsies were stained with MxA and scored. Clinical data at initial presentation were collected and autoantibodies were analysed. Multiple linear regression analysis was performed to estimate the association between MxA expression on muscle fibres and muscle disease activity, and MSA status. RESULTS: Expression of MxA protein on JDM samples was identified in 61.2%. There was a significant association between MxA scores and Childhood Myositis Assessment Scale (CMAS) (P = 0.002), and Manual Muscle Testing of Eight Muscles (MMT8) (P = 0.026). CMAS and MMT8 scores were significantly lower in the group of patients with strong MxA expression. MxA scores differed according to MSA subgroups (P = 0.002). Patients with positive nuclear matrix protein 2 autoantibodies had strong MxA expression, whereas anti-melanoma differentiation-associated gene 5 positive patients had no or weak MxA expression. CONCLUSIONS: This study reveals the significant association between level of MxA expression on muscle fibres and clinical measures of muscular disease activity in JDM patients and MSA status. This confirms type I interferonopathies in muscle fibres of JDM patients which could help with improving treatment outcome in JDM patients and underscoring the distinct pathophysiological pathways in different MSA status.

[Thoracoabdominal muscle involvement in anti-PL-7 myopathy revealed by whole-body magnetic resonance imaging].

A 33-year-old woman developed progressive weakness in the proximal limbs with myalgia and morning stiffness. Physical examination revealed low-grade fever, heliotrope eyelids and mechanic's hand. On neurological examination, she showed Medical Research Council grade 4 weakness in the shoulder girdle, proximal limb muscles, and grade 4 weakness in the abdominis muscle according to Daniels's scale. Laboratory tests revealed elevated serum creatine kinase (6,824 IU/l) and positive anti-PL-7 antibody. A needle electromyography study detected short motor unit potentials of myogenic pattern with abundant fibrillations and positive sharp waves. Whole-body MRI detected high intensity signals in the muscles of the shoulder girdle, proximal limbs, and thoracoabdominal trunk on short-tau inversion recovery sequence images. We diagnosed her as anti-PL-7 myopathy. After treatments with steroid, immunosuppressant, and immunoglobulin, her symptoms improved and abnormal MRI signals were normalized. Although MRI is known to be useful for detection of asymptomatic muscular inflammation in myositis, thoracoabdominal muscles are generally not covered in routine evaluation. To our knowledge, ours is the first case to detect acute inflammation of the thoracoabdominal muscles in antisynthetase syndrome. The present study suggests that whole-body MRI is useful for comprehensive evaluation of muscular involvement and longitudinal assessment for treatment outcomes.