Distinct tissue injury patterns in juvenile dermatomyositis auto-antibody subgroups

Nguyen, Mailan; Do, Vy; Yell, Paul C.; Jo, Chan-Hee; Liu, Jie; Burns, Dennis K.; Wright, Tracey; Cai, Chunyu

doi:10.1186/s40478-020-01007-3

Cited by 17 publications

(30 citation statements)

References 35 publications

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“…Anti-NXP-2 was distinctively associated with microinfarctions, features described in regional ischemic immune myopathy (RIIM). 26 Although few cases have been reported describing muscle ischemia or clustered necrosis in juvenile anti-NXP-2 DM, 18, 19 we provide the first evidence that adult and juvenile anti-NXP-2 DM were equally affected by microinfarction. Since the percentage of microinfarctions in adult and juvenile anti-NXP-2 DM were not significantly different, this phenomenon could not simply be explained by different CFRs between the two age groups.…”

Section: Discussionmentioning

confidence: 55%

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Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Tanboon

Inoue

Saito

et al. 2021

Preprint

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Importance: Current pathological criteria of dermatomyositis (DM) do not recognize different features among DM subtypes classified by dermatomyositis-specific antibodies (DMSAs). Objective: To determine whether myopathological features differ among DM subtypes classified by DMSAs and whether the pathological features can be characterized by serologically defined DM subtype. Design: Retrospective review of muscle pathology slides of 256 patients diagnosed with DM from January 2009 to December 2020. Setting: Single center study in a tertiary laboratory for muscle diseases. Participants: A total of 256 patients whose DM diagnosis was pathologically confirmed based on the sarcoplasmic expression of myxovirus resistant protein A (MxA) were included. Of these, 249 patients were positive for one of the 5 DMSAs (seropositive patients, anti-TIF1-γ=87, anti-Mi-2=40, anti-MDA5=29, anti-NXP-2=83, and anti-SAE=10), and 7 were negative for all 5 DMSAs (seronegative patients). Exposure: Histochemical, enzyme histochemical, immunohistochemical staining, and ultrastructural study. Main outcomes and measures: Histological features stratified according to four pathology domains: muscle fiber, inflammatory, vascular, and connective tissue domains, and histological features of interest by histochemistry, enzyme histochemistry, and immunohistochemical study commonly used in the diagnosis of inflammatory myopathy. Results: DMSAs significantly associated with characteristic histochemical and immunohistochemical features were as follows: anti-TIF1-γ with vacuolated/punched out fibers (64.7%, P<.001) and perifascicular enhancement in HLA-ABC (75.9%, P<.001); anti-Mi-2 with prominent muscle fiber damage (score 4.8±2.1, P<.001), inflammatory cell infiltration (score 8.0±3.0, P=.002), perifascicular atrophy (67.5%, P=.02), perifascicular necrosis (52.5%, P<.001), increased perimysium alkaline phosphatase activity (70.0%, P<.001), central necrotic peripheral regenerating fibers (45.0%, P<.001), and sarcolemmal deposition of the membrane attack complex (67.5%, P<.001); anti-MDA5 with scattered/diffuse staining pattern of MxA (65.5%, P<.001) with less muscle pathology and inflammatory features; and anti-NXP2 with microinfarction (26.5%, P<.001); and anti-SAE and seronegative DM with HLA-DR expression (50.0%, P=.02 and 57.1%, P=.02 respectively). Conclusion and relevance: We described an extensive study on serological-pathological correlation of DM primarily using MxA expression as an inclusion criterion. DMSAs was associated with distinctive myopathological features in our studied cohort, suggesting that different pathobiological mechanisms may underscore each subtype.

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Section: Discussionmentioning

confidence: 55%

“…16,17 Conversely, DMSA-associated pathological phenotypes have been limited to small studies. 8, 11-13,18,19 This study aimed to investigated and characterize DMSA-specific pathological features.…”

Section: Introductionmentioning

confidence: 99%

Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Tanboon

Inoue

Saito

et al. 2021

Preprint

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“…Mi‐2 + patients had more primary inflammation, NXP2 + patients had less primary inflammation and TIF1γ + patients had more mitochondrial dysfunction 13 . Nguyen et al also reported the MSA specific tissue injury and speculated that there might be tissue specific receptors for the different types of MSA 22 …”

Section: Discussionmentioning

confidence: 99%

“…21 Allenbach et al observed that only anti-MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic, not classic DM, also indicating the different pattern of mitochondrial 13 Nguyen et al also reported the MSA specific tissue injury and speculated that there might be tissue specific receptors for the different types of MSA. 22 IFN appears to play a key role in the pathogenesis of idiopathic inflammatory myopathies, especially in DM. 23 An up-regulated IFN signature has been observed in skeletal muscle, skin samples, and peripheral blood mononuclear cells of anti-MDA5 DM.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial morphology and MAVS‐IFN1 signaling pathway in muscles of anti‐MDA5 dermatomyositis

Jiang¹,

Liu²,

Zhao³

et al. 2021

Ann Clin Transl Neurol

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Objective This study aimed to investigate mitochondrial changes and the mitochondrial antiviral‐signaling protein (MAVS)‐type I interferon (IFN1) signaling pathway in the muscles of anti‐melanoma differentiation gene 5(MDA5) dermatomyositis (DM) patients. Methods Eleven anti‐MDA5 DM and ten antibody‐negative DM patients were included. Muscle biopsies were performed in all patients. Muscle pathology and mitochondrial morphology in particular were compared between two groups. The expression of MDA5, MAVS, interferon (IFN) regulatory factor 7, and IFN‐stimulated gene 15, which are components of the MAVS‐IFN1 signaling pathway, was measured in muscle specimen. The correlation between MAVS expression in muscles and disease phenotypes and muscle pathology were analyzed. Results Anti‐MDA5 DM showed a significantly lower incidence of the characteristic DM pathology (P < 0.05) than antibody‐negative DM, including perifascicular fiber atrophy, inflammation, and vasculopathy. Mitochondrial abnormalities in anti‐MDA5 patients revealed a high incidence of (8/11,72.7%) and different pattern from that in antibody‐negative DM. MDA5, MAVS, IFN regulatory factor 7, and IFN stimulated gene 15 expression levels in the muscles of anti‐MDA5 DM patients were higher than those of the controls (P < 0.05) but lower than those of antibody‐negative DM patients (P < 0.05). The MAVS levels negatively correlated with manual muscle test 8 scores (r = 0.701, P = 0.016). Conclusions Compared to antibody‐negative DM, we presented a different distribution of the mitochondrial pathology and less severe morphology in anti‐MDA5 DM. We also revealed the enhanced but less intensive MAVS‐IFN1 signaling pathway activity in muscles of anti‐MDA5 DM. Such disparity suggested the potentially different mechanism of muscle injury in two DM groups.

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“…[ 10 ] Previous data have shown that anti-NXP2 autoantibodies are present in 23% to 30.2% of juvenile DM and less than 17% of adult PM/DM. [ 9 , 11 ] In an Argentine pediatric myositis cohort, anti-NXP2 antibodies were likely linked to muscle contractures, atrophy and significant functional compromise. [ 12 ] Additionally, anti-NXP2 autoantibodies detected in DM were found to be more significantly associated with calcinosis in younger patients and cancer in older male adults.…”

Section: Discussionmentioning

confidence: 99%

Multiple neurological manifestations in a patient with systemic lupus erythematosus and anti-NXP2-positive myositis

Cao

Zhang

et al. 2021

Medicine

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Rationale: Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory disease that frequently affects various organs. Neuropsychiatric manifestations in SLE patients, known as neuropsychiatric SLE, are clinically common. However, the principal manifestation of cranial neuropathy in patients with SLE and comorbidities is relatively rare. Patient concerns: In this report, we describe a 51-year-old Chinese woman who was admitted with a chief complaint of chronic-onset facial paresthesia, dysphagia, and choking cough when drinking water, accompanied by slurred speech, salivation, and limb weakness. The blood autoantibody test results showed that many SLE-associated antibodies were positive. Meanwhile, anti-nuclear matrix protein 2 (NXP2) antibody was strongly positive in the idiopathic inflammatory myopathy (IIM) spectrum test from the serum. Muscle biopsy indicated inflammatory infiltration of the muscle fiber stroma. Diagnoses: Taking into account the clinical manifestations and laboratory tests of the present case, the diagnosis of SLE and probable IIM was established. Interventions: Corticosteroids and additional gamma globulin were administered and the clinical symptoms were relieved during the treatment process. Outcomes: Unfortunately, the patient experienced sudden cardiac and respiratory arrest. Multiple system dysfunctions exacerbated disease progression, but in the present case, we speculated that myocardial damage resulting from SLE could explain why she suddenly died. Lessons: To our knowledge, multiple neurological manifestations in patients with SLE and anti-NXP2-positive myositis are rare. Note that SLE is still a life-threatening disease that causes multiple system dysfunctions, which requires increasing attention.

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Distinct tissue injury patterns in juvenile dermatomyositis auto-antibody subgroups

Cited by 17 publications

References 35 publications

Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Mitochondrial morphology and MAVS‐IFN1 signaling pathway in muscles of anti‐MDA5 dermatomyositis

Multiple neurological manifestations in a patient with systemic lupus erythematosus and anti-NXP2-positive myositis

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