The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody

Nakashima, Ran; Imura, Yoshitaka; Kobayashi, Shio; Yukawa, Naoichiro; Yoshifuji, Hajime; Nojima, Takaki; Kawabata, Daisuke; Ohmura, Koichiro; Usui, Takashi; Fujii, Tomoyuki; Okawa, Katsuya; Mimori, Tsuneyo

doi:10.1093/rheumatology/kep375

Cited by 307 publications

(306 citation statements)

References 31 publications

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“…7,8 The development and rapid progression of ILD may account for the significantly higher mortality observed in anti-MDA5-positive-DM patients as compared to serologically negative cohorts. 6,14,18,19 Generally, skin manifestations precede ILD in these patients. 14 Previous studies have shown a correlation between ferritin levels and ILD activity, as well as an association between elevated ferritin levels and mortality in patients with anti-MDA5-positive-DM.…”

Section: Discussionmentioning

confidence: 99%

Anti-MDA5-Positive Dermatomyositis Presenting as Fever of Unknown Origin

et al. 2016

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Dermatomyositis is a chronic systemic autoimmune disease characterized by inflammatory infiltrates in the skin and muscle. The wide variability in clinical and serologic presentation poses a diagnostic challenge for the internist. Appreciation of the clinical variants of dermatomyositis allows for expedient diagnosis and avoidance of diagnostic error. We illustrate these challenges with the case of a 51-year-old VietnameseAmerican man who initially presented with fever of unknown origin in the absence of overt skin and muscle manifestations. The diagnosis of dermatomyositis was not evident on several clinical encounters due to the absence of these hallmark symptoms. We review the variable clinical manifestations of a subtype of dermatomyositis associated with an autoantibody against melanoma differentiation-associated protein 5 (anti-MDA5) and suggest consideration of dermatomyositis as a diagnosis in patients presenting with systemic illness and markedly elevated ferritin, even in the absence of elevated muscle enzymes and classic autoantibodies. CASE PRESENTATIONA 51-year-old Vietnamese-American male industrial engineer was admitted to the medical ward for evaluation of fever of unknown origin (FUO). He reported 3 weeks of fever, fatigue, generalized weakness, and dyspnea. His past medical history included a remote 10-pack-year history of cigarette smoking and latent tuberculosis treated with 9 months of isoniazid treatment, completed 5 years prior. He had moved from Vietnam to the United States 30 years earlier and denied any recent travel, sick contacts, or insect bites. Physical examination revealed a fatigued man, with a temperature of 38.1°C, pulse of 108 beats/minute, respiratory rate of 28 breaths/minute, and room air oxygen saturation of 96 %. Oropharyngeal, neurologic, pulmonary, cardiac, musculoskeletal, and skin evaluation were otherwise normal.A complete blood count (CBC) revealed anemia (hemoglobin 12.3 g/dL, hematocrit 38.5 %). White blood cell counts, platelet counts, and the basic metabolic panel were normal. Erythrocyte sedimentation rate (ESR) was 97 mm/hr and C-reactive protein (CRP) was 5.7 mg/dL. Muscle enzymes, sent to evaluate his weakness in the setting of elevated inflammatory markers, showed normal creatine kinase (CK) at 44 units/liter and mildly elevated aldolase to 9.4 U/L (normal: < 7.7 U/L). Blood, urine, and sputum cultures had no growth. Chest x-ray (CXR) demonstrated low lung volumes with increased reticular markings, small bilateral pleural effusions, and bibasilar opacities. During the hospitalization, he continued to have intermittent fevers as high as 39.1°C, generalized weakness, and dyspnea. Additionally, he developed bibasilar crackles on pulmonary exam and flat, diffuse, slightly hyperpigmented patches on his arms and chest that faded over several days. Extensive workup for infectious, inflammatory, and malignant causes of fever was unrevealing, including negative viral hepatitis serologies, human immunodeficiency virus antibody, anti-nuclear antibody (ANA), and anti-...

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Section: Discussionmentioning

confidence: 99%

Anti-MDA5-Positive Dermatomyositis Presenting as Fever of Unknown Origin

et al. 2016

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“…Therefore, anti-CADM140 antibody was also named anti-MDA-5 antibody and was known to be associated with CADM and ILD in recent publications (11)(12)(13)(14). To establish the clinical relevance of anti-MDA-5 antibodies, we examined the antibody in the sera of Chinese patients with various connective tissue diseases (CTDs), and further delineated the clinical course of patients with a positive expression of anti-MDA-5 antibodies.…”

Section: Introductionmentioning

confidence: 99%

Clinical manifestations of dermatomyositis and clinically amyopathic dermatomyositis patients with positive expression of anti–melanoma differentiation–associated gene 5 antibody

Cao¹,

Pan²,

Kang³

et al. 2012

Arthritis Care & Research

167

165

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“…RIG-I and IFIH1 interact with viral RNA and mediate signalling pathways leading to the transcription of type I interferons (IFNs) and inflammatory cytokines (Takeuchi & Akira, 2008). The finding that IFIH1 provokes MSA reinforces the idea of an association between myositis and viral infection: self-tolerance might be broken when IFIH1 interacts with certain viral RNAs and generates cryptic epitopes or when elevated IFN-levels up-regulate IFIH1 synthesis, resulting in over-expression and release from damaged cells (Nakashima, 2010). It is not well understood how a self-molecule can be singled out as target for autoantibody response.…”

Section: Autoantibodiesmentioning

confidence: 87%

“…Anti-small ubiquitin-like modifier activating enzyme (SAE) antibodies are found in about 8% of DM patients (Ghirardello et al, 2010). A novel MSA -anti-CADM-140 antibody -was identified recently in a Japanese cohort of DM patients (Nakashima et al, 2010). These antibodies seem particularly associated with clinically amyopathic DM who also have acute progressive interstitial lung disease.…”

Section: Autoantibodiesmentioning

confidence: 99%

Idiopathic Inflammatory Myopathies: A Review of Immunopathological Features and Current Models of Pathogenesis

Cappelletti¹,

Morandi²,

Mora³

et al. 2011

Idiopathic Inflammatory Myopathies - Recent Developments

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The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody

Abstract: The anti-CADM-140 antibody was a marker of DM and intractable ILD and recognized IFIH1/MDA5, which is involved in innate immunity. These findings may give a new insight into the pathogenesis of DM.

Cited by 307 publications

References 31 publications

Anti-MDA5-Positive Dermatomyositis Presenting as Fever of Unknown Origin

Anti-MDA5-Positive Dermatomyositis Presenting as Fever of Unknown Origin

Clinical manifestations of dermatomyositis and clinically amyopathic dermatomyositis patients with positive expression of anti–melanoma differentiation–associated gene 5 antibody

Idiopathic Inflammatory Myopathies: A Review of Immunopathological Features and Current Models of Pathogenesis

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