Pathologic Features of Anti-Mi-2 Dermatomyositis

Tanboon, Jantima; Inoue, Michio; Hirakawa, Shinya; Tachimori, Hisateru; Hayashi, Shinichiro; Noguchi, S.; Suzuki, Shigeaki; Okiyama, Naoko; Fujimoto, Manabu; Nishino, Ichizo

doi:10.1212/wnl.0000000000011269

Cited by 34 publications

(66 citation statements)

References 47 publications

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“…The CFR value in all adult DM (0.7±0.3) was lower than the value in 12 normal adult muscle biopsy (1.1±0.1, P <.001). 11 The CFR did not significantly differ among DMSA subtypes (Figure 2C,D). Anti-Mi-2 DM were more commonly associated with increased ALP activity in the perimysium (70.0% vs. non-Mi-2 29.5%, P <.001).…”

Section: Resultsmentioning

confidence: 86%

“…Histological features in anti-Mi-2 DM were compatible with those previously described in immune myopathy with perimysial pathology (IMPP). 11,18 By comparing each DMSA with other subtypes, anti-Mi-2 was significantly associated with PFA, 11,13 PFN, 11,18 PM-ALP, 11,18 inflammatory features, 11-13 perifascicular MxA expression, and sarcolemmal MAC expression. 11,13,18 We confirmed that anti-TIF1-γ DM was significantly associated with vacuolated fibers, 8 HLA-ABC expression with perifascicular enhancement and distinctive capillary MAC deposition.…”

Section: Discussionmentioning

confidence: 99%

“…The histochemical and immunohistochemical stained slides, prepared at the time of pathological diagnosis at the NCNP, were evaluated based on 4 domains (muscle fiber, inflammatory, vascular, and connective tissue domains) using the same scoring system as our previous studies modified from the pathology scoring system originally used for juvenile DM (supplement and eTable 1). 11, 24 Alongside the PFA, perifascicular necrosis (PFN), decreased cytochrome c oxidase (COX) activity in perifascicular area, perivascular vascular inflammation, vasculitis, CD8 and acid phosphatase (ACP)/CD68 infiltration in non-necrotic fiber, and CD20 aggregation, we included microinfarction, centrally necrotic-and-peripherally regenerating (CNPR) fibers, and vacuolated/punched-out fiber as histopathology of interest for DM. Microinfarction was defined by the aggregate of at least 3 necrotic fibers without inflammatory cell infiltration into the necrotic fiber accompanied by decreased/absent sarcoplasmic oxidative enzymatic activity on nicotinamide adenine dinucleotide dehydrogenase-tetrazolium reductase.…”

Section: Methodsmentioning

confidence: 99%

“…2 In addition to perifascicular atrophy (PFA), the best known pathological feature of DM, the 2018 ENMC-DM included myofiber expression of myxovirus resistant protein A (MxA), the surrogate marker for type I interferon (IFN1) pathway activation, as a diagnostic finding. 4-7 Interestingly, DMSA-associated clinical phenotypes have been characterized, including anti-TIF1-γ DM with DM skin lesions, dysphagia, and malignancy; 8-10 anti-Mi-2 DM with high serum creatine kinase (CK) level, myalgia, and muscle weakness; 11-13 anti-MDA5 DM with mechanic hands and interstitial lung disease (ILD), but low CK levels and less muscle involvement; 14, 15 and anti-NXP-2 DM with muscle weakness, but less skin involvement. 16,17 Conversely, DMSA-associated pathological phenotypes have been limited to small studies.…”

Section: Introductionmentioning

confidence: 99%

“…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%

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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: Resultsmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Tanboon

Inoue

Saito

et al. 2021

Preprint

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Clinicopathological and circulating cell‐free DNA profile in myositis associated with anti‐mitochondrial antibody

Wang,

Zhao,

et al. 2023

Ann Clin Transl Neurol

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ObjectiveAnti‐mitochondrial antibodies (AMAs) are associated with idiopathic inflammatory myopathies (IIMs). We aimed to summarize the clinicopathological characteristics, assess circulating cell‐free mitochondrial DNA (ccf‐mtDNA), and circulating cell‐free nuclear DNA (ccf‐nDNA) in AMA‐associated IIMs.MethodsMedical records of 37 IIMs patients with AMAs were reviewed. Circulating cell‐free mtDNA and ccf‐nDNA levels in sera from IIMs patients with AMAs (n = 21), disease controls (n = 66) and healthy controls (HCs) (n = 23) were measured and compared. Twenty‐eight immune‐mediated necrotizing myopathy (IMNM) patients, 23 dermatomyositis (DM) patients, and 15 anti‐synthetase syndrome (ASS) patients were enrolled as disease controls. Correlations between variables were analyzed.ResultsLimb weakness was observed in 75.7% and neck weakness in 56.8% of patients. Cardiac involvement occurred in 51.4% of patients. Muscle pathology revealed 81.1% of IMNM, 5.4% polymyositis, and 13.5% nonspecific myositis. Microinfarction was observed in 8.1% of patients. Serum ccf‐mtDNA levels in AMA‐associated IIMs were significantly higher than those in HCs (p < 0.001), but no significant differences between AMA‐associated IIMs and IMNM, DM, or ASS. Serum ccf‐nDNA levels in AMA‐associated IIMs were significantly higher than those in HCs (p = 0.02), and significantly lower than those in DM (p = 0.02). Serum ccf‐nDNA levels correlated negatively with MMT8 total scores (rs = −0.458, p = 0.037) and positively with mRS scores (rs = 0.486, p = 0.025). Serum ccf‐nDNA levels were significantly higher in the non‐remission group (p < 0.01).InterpretationAMA‐associated IIMs exhibit distinct clinicopathological features. Serum ccf‐nDNA may serve as a potential marker for disease severity and prognosis in AMA‐associated IIMs.

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Correlation of muscle ultrasound with clinical and pathological findings in idiopathic inflammatory myopathies

et al. 2023

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Introduction/Aims In idiopathic inflammatory myopathies (IIMs), the change in muscle echogenicity and its histopathological basis are not well understood. We quantitatively measured muscle echogenicity in patients with IIMs and evaluated its correlation with disease activity and histopathological findings. Methods This study involved patients with IIMs who underwent both ultrasonography (US) and muscle biopsy, as well as age‐ and sex‐matched rheumatoid arthritis patients as inflammatory disease controls. On US, axial images of the right biceps brachii and vastus medialis were obtained. Standardized histopathological scoring was used to quantitatively measure each pathological domain. Results Forty‐two patients (17 with inclusion body myositis [IBM] and 25 with IIMs other than IBM) and 25 controls were included. The muscle echo intensity (EI) of patients with IIMs was significantly higher than that of controls. Muscle EI showed significant correlations with creatine kinase (r = 0.66, p < .001) and muscle strength (r = −0.73, p < .0001) in patients with non‐IBM IIMs. In patients with IBM, moderate correlation was found between muscle EI and quadriceps muscle strength (r = −0.53, p = .028). Histopathologically, the number of infiltrating CD3+ inflammatory cells correlated with muscle EI in the non‐IBM group (r = 0.56, p = .017), but not in the IBM group. Discussion Muscle EI may be useful as a surrogate marker of muscle inflammation in non‐IBM IIM. Increased muscle EI may be difficult to interpret in patients with long‐standing IBM, which has advanced and complex histopathology.

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Pathologic Features of Anti-Mi-2 Dermatomyositis

Cited by 34 publications

References 47 publications

Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Clinicopathological and circulating cell‐free DNA profile in myositis associated with anti‐mitochondrial antibody

Correlation of muscle ultrasound with clinical and pathological findings in idiopathic inflammatory myopathies

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