Advances in Juvenile Dermatomyositis: Myositis Specific Antibodies Aid in Understanding Disease Heterogeneity

Pachman, Lauren M.; Khojah, Amer

doi:10.1016/j.jpeds.2017.12.053

Cited by 64 publications

(68 citation statements)

References 143 publications

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“…Among the IRG-S of MSA group patients, the anti-MDA5 autoantibody-positive IRG-S overlapped most closely with SAVI by PCA. The anti-MDA5 autoantibody subgroup of JDM is characterized by increased cutaneous ulceration and interstitial lung disease (ILD) with less muscle disease [1][2][3], also observed in our cohort, with more overlap with these vasculopathic features seen in SAVI than CANDLE in general [15][16][17], also specifically observed in our cohort. JAK inhibitor therapy has been noted to show improved outcomes in refractory anti-MDA5 autoantibody adult and juvenile dermatomyositis, including with rapidly progressive ILD [36][37][38].…”

Section: Discussionsupporting

confidence: 77%

“…All of the SAVI patients with available data (4/4, 100%) had interstitial lung disease versus 8/56 (14.3%) of JDM and none of the CANDLE patients. Of note, there is some variation within JDM by the MSA group as previously described [1][2][3][4]. The anti-TIF1 autoantibody JDM subgroup has more photosensitivity (18/20, 90.0%) and shawl sign rash (8/20, 55.0%) versus other groups in JDM.…”

Section: Description Of Clinical Featuresmentioning

confidence: 63%

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Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies

et al. 2020

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Background: Juvenile dermatomyositis (JDM) is a systemic autoimmune disease with a prominent interferon (IFN) signature, but the pathogenesis of JDM and the etiology of its IFN signature remain unknown. The Mendelian autoinflammatory interferonopathies, Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) and STING-Associated Vasculopathy with onset in Infancy (SAVI), are caused by genetic mutations and have extremely elevated IFN signatures thought to drive pathology. The phenotypic overlap of some clinical features of CANDLE and SAVI with JDM led to the comparison of a standardized interferon-regulated gene score (IRG-S) in JDM and myositis-specific autoantibody (MSA) JDM subgroups, with CANDLE and SAVI. Methods: A peripheral 28-component IRG-S assessed by NanoString™ in 57 JDM patients subtyped by MSA was compared with IRG-S in healthy controls (HC) and CANDLE/SAVI patients. Principal component analysis (PCA) was performed, and individual genes were evaluated for their contribution to the score. IRG-S were correlated with disease assessments and patient characteristics. Results: IRG-S in JDM patients were significantly higher than in HC but lower than in CANDLE or SAVI. JDM IRG-S overlapped more with SAVI than CANDLE by PCA. Among MSA groups, anti-MDA5 autoantibody-positive patients' IRG-S overlapped most with SAVI. The IFI27 proportion was significantly higher in SAVI and CANDLE than JDM, but IFIT1 contributed more to IRG-S in JDM. Overall, the contribution of individual interferon-regulated genes (IRG) in JDM was more similar to SAVI. IRG-S correlated moderately with JDM disease activity measures (r s = 0.33-0.47) and more strongly with skin activity (r s = 0.58-0.79) in anti-TIF1 autoantibody-positive patients. Weakness and joint disease activity (multinomial OR 0.91 and 3.3) were the best predictors of high IRG-S.

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Section: Discussionsupporting

confidence: 77%

Section: Description Of Clinical Featuresmentioning

confidence: 63%

Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies

et al. 2020

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“…Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of systemic autoimmune diseases characterised by weakness, chronic inflammation of skeletal muscles and elevated serum muscle enzyme levels 1. Many patients also have extramuscular manifestations, including involvement of the skin, lungs and/or joints.…”

Section: Introductionmentioning

confidence: 99%

Anti-Ro52 autoantibodies are associated with interstitial lung disease and more severe disease in patients with juvenile myositis

et al. 2019

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ObjectivesAnti-Ro52 autoantibodies are associated with more severe interstitial lung disease (ILD) in adult myositis patients with antiaminoacyl transfer (t)RNA synthetase autoantibodies. However, few studies have examined anti-Ro52 autoantibodies in juvenile myositis. The purpose of this study was to define the prevalence and clinical features associated with anti-Ro52 autoantibodies in a large cohort of patients with juvenile myositis.MethodsWe screened sera from 302 patients with juvenile dermatomyositis (JDM), 25 patients with juvenile polymyositis (JPM) and 44 patients with juvenile connective tissue disease–myositis overlap (JCTM) for anti-Ro52 autoantibodies by ELISA. Clinical characteristics were compared between myositis patients with and without anti-Ro52 autoantibodies.ResultsAnti-Ro52 autoantibodies were found in 14% patients with JDM, 12% with JPM and 18% with JCTM. Anti-Ro52 autoantibodies were more frequent in patients with antiaminoacyl tRNA synthetase (64%, p<0.001) and anti-MDA5 (31%, p<0.05) autoantibodies. After controlling for the presence of myositis-specific autoantibodies, anti-Ro52 autoantibodies were associated with the presence of ILD (36% vs 4%, p<0.001). Disease course was more frequently chronic, remission was less common, and an increased number of medications was received in anti-Ro52 positive patients.ConclusionsAnti-Ro52 autoantibodies are present in 14% of patients with juvenile myositis and are strongly associated with anti-MDA5 and antiaminoacyl tRNA synthetase autoantibodies. In all patients with juvenile myositis, those with anti-Ro52 autoantibodies were more likely to have ILD. Furthermore, patients with anti-Ro52 autoantibodies have more severe disease and a poorer prognosis.

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“…The etiology of JDM is not well characterized, but both adaptive and innate immune responses have been associated with JDM pathogenesis. Myositis-specific and myositis-associated antibodies (against extractable nuclear antigens) have been identified in approximately 65% of JDM patients (3,4). Furthermore, B cell depletion with rituximab (a chimeric monoclonal antibody against CD20) leads to clinical improvement in some JDM patients (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Dysregulated NK cell PLCγ2 signaling and activity in juvenile dermatomyositis

et al. 2018

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Advances in Juvenile Dermatomyositis: Myositis Specific Antibodies Aid in Understanding Disease Heterogeneity

Cited by 64 publications

References 143 publications

Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies

Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies

Anti-Ro52 autoantibodies are associated with interstitial lung disease and more severe disease in patients with juvenile myositis

Dysregulated NK cell PLCγ2 signaling and activity in juvenile dermatomyositis

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