Necrosis in anti-SRP
            <sup>+</sup>
            and anti-HMGCR
            <sup>+</sup>
            myopathies

Allenbach, Yves; Arouche-Delaperche, Louiza; Preuße, Corinna; Radbruch, Helena; Butler‐Browne, Gillian; Champtiaux, Nicolas; Mariampillai, K.; Rigolet, Aude; Hufnagl, Peter; Zerbe, Norman; Amelin, D.; Maisonobe, Thierry; Louis-Léonard, S.; Duyckaerts, Charles; Eymard, B.; Goebel, Hans‐Hilmar; Bergua, Cécile; Drouot, Laurent; Boyer, Olivier; Benveniste, Olivier; Stenzel, Werner

doi:10.1212/wnl.0000000000004923

Cited by 136 publications

(89 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, even if the subacute onset (<6 months) was noted for most of the patients, 33% of patients had a slow progressive muscular deficit ranging from 10 months to several years (three cases had been considered to be MD for more than 10 years prior to the detection of the anti-HMGCR antibodies). 4 The slow progression was also observed in a previous report of an anti-SRP antibodies-related NAM. 8 The co-occurrence of other autoimmune disorders may be found in patients presenting a NAM and could suggest the NAM diagnosis.…”

Section: Discussionsupporting

confidence: 76%

“…In fact, Allenbach et al identified eight autoimmune diseases in the medical history of 5 patients among 45 (thyroiditis in 4 and type 1 diabetes in 1). 4 In our case, the patient developed type 1 diabetes. In a recent cohort of juvenile myositis, 5 out of 440 patients were HMGCR positive and had more frequent joint contractures and arthralgias that may also suggest the diagnosis.…”

Section: Discussionmentioning

confidence: 53%

“…4 C5b-9 deposit was frequently (65%) observed on necrotic fibers but also on the membrane of a few normal ones and on a few muscle capillaries (25%) though dramatically less than in the typical dermatomyositis. 4 The differential diagnosis with MDs may thus be very complex 12 ; immunohistochemical analysis (sometimes weak and focal MHC class I antigen sarcolemma expression) and cell phenotyping (showing that necrotic fibers can be invaded by macrophages, which are the predominant mononuclear cell type, whereas T and B cells are virtually absent) may be helpful. In addition, inflammation, when present, was usually localized in perivascular areas.…”

Section: Discussionmentioning

confidence: 99%

“…NAM often accompanies statin therapy (35% of cases), connective tissue diseases, and cancer. 2,4 However, half of the patients constituting the idiopathic subgroup of NAM have no identifiable risk factors.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Anti-HMGCR Antibody–Related Necrotizing Autoimmune Myopathy Mimicking Muscular Dystrophy

et al. 2017

View full text Add to dashboard Cite

Introduction Necrotizing autoimmune myopathies (NAMs) are acquired myopathies with myofibrillar necrosis and weak or absent inflammatory component, sometimes associated with anti-signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. Observation The patient, a girl now aged 20 years, was first assessed at the age of 5 years for abnormal gait revealing frank pelvic deficit. Creatine kinase (CK) levels were as high as 7,500 IU/L. Subsequent muscle biopsy showed some necrosis, fiber regeneration, and fibrosis consistent with muscular dystrophy (MD). Protein immunohistochemistry was normal. The disease course was progressive until wheelchair use at the age of 9 years. At 12 years of age, a second muscle biopsy found an advanced MD with some perivascular inflammatory mononuclear cells. All molecular analyses done through 14 years of follow-up were negative till anti-HMGCR antibodies were detected at a significant amount when she was 19 years old. Discussion NAMs begin at a pediatric age and may have a chronic course mimicking MDs. Muscular biopsy can be misleading with a predominantly dystrophic pattern without inflammation. Conclusion This observation should prompt the assessment of NAMs in all MDs, even pediatric, without molecular solutions.

show abstract

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Anti-HMGCR Antibody–Related Necrotizing Autoimmune Myopathy Mimicking Muscular Dystrophy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Some experts have argued for the specific utility of rituximab in patients with anti-SRP-antibodies. Recent work has supported the pathogenic role of anti-SRP and anti-HMGCR antibodies in IMNM [144,145], and disease severity has been shown to correlate with antibody titers in anti-SRP myopathy patients [146]. Although a case series suggested that there is a significant reduction in anti-SRP titers after rituximab [147], post hoc analysis from the RIM trial failed to show a significant decrease after rituximab [148].…”

Section: Choice Of Second-line Agentsmentioning

confidence: 99%

Autoimmune Myopathies: Updates on Evaluation and Treatment

2018

View full text Add to dashboard Cite

The major forms of autoimmune myopathies include dermatomyositis (DM), polymyositis (PM), myositis associated with antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). While each of these conditions has unique clinical and histopathological features, they all share an immune-mediated component. These conditions can occur in isolation or can be associated with systemic malignancies or connective tissue disorders (overlap syndromes). As more has been learned about these conditions, it has become clear that traditional classification schemes do not adequately group patients according to shared clinical features and prognosis. Newer classifications are now utilizing myositis-specific autoantibodies which correlate with clinical and histopathological phenotypes and risk of malignancy, and help in offering prognostic information with regard to treatment response. Based on observational data and expert opinion, corticosteroids are considered first-line therapy for DM, PM, ASS, and IMNM, although intravenous immunoglobulin (IVIG) is increasingly being used as initial therapy in IMNM related to statin use. Second-line agents are often required, but further prospective investigation is required regarding the optimal choice and timing of these agents.

show abstract

CD163+ macrophage density in perimysial connective tissue associated with prognosis in IMNM

Sun,

Wang,

Han

et al. 2024

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveThe pathological features of immune‐mediated necrotizing myopathy (IMNM) are dominated by the infiltration of macrophages. We aimed to perform a histopathologic semiquantitative analysis to investigate the relationship between macrophage markers and prognosis.MethodsSemiquantitative analysis of histologic features was performed in 62 samples of IMNM. Independent risk factors were identified through univariate and multivariate regression analysis. Cluster analysis was performed using the partitioning around the medoids (PAM) method. Decision tree modeling was utilized to efficiently determine cluster labels for IMNM patients. The validity of the developmental cohort was assessed by accuracy in comparison with the validation cohort.ResultsThe most enriched groups in patients with IMNM were macrophages expressing CD206 and CD163. In the multivariate logistic regression model, the high density of CD163+ macrophages in perimysial connective tissue increased the risk of unfavorable prognosis (p = 0.025, OR = 1.463, 95% CI: 1.049–2.041). In cluster analysis, patients in Cluster 1, with lower CD163+ macrophage density and inflammatory burden, had a more favorable prognosis. Conversely, patients in Cluster 3, which were enriched for CD163+ macrophages in the perimysial connective tissue, had the most severe clinical features and the worst prognosis. Correlations were found between the density of CD163+ macrophages in connective tissue and symptom duration (R2 = 0.166, p < 0.001), dysphagia (p = 0.004), cardiac involvement (p = 0.021), CK (R2 = 0.067, p = 0.042), CRP (R2 = 0.117, p < 0.001), and ESR (R2 = 0.171, p < 0.001).ConclusionThe density of CD163+ macrophages in perimysial connective tissue may serve as a potential marker for the prediction of IMNM prognosis.

show abstract

Necrosis in anti-SRP ⁺ and anti-HMGCR ⁺ myopathies

Abstract: These data further corroborate the pathogenic role of anti-SRP and anti-HMGCR autoantibodies in IMNM, highlighting humoral mechanisms as key players in immunity and myofiber necrosis.

Cited by 136 publications

References 29 publications

Anti-HMGCR Antibody–Related Necrotizing Autoimmune Myopathy Mimicking Muscular Dystrophy

Anti-HMGCR Antibody–Related Necrotizing Autoimmune Myopathy Mimicking Muscular Dystrophy

Autoimmune Myopathies: Updates on Evaluation and Treatment

CD163+ macrophage density in perimysial connective tissue associated with prognosis in IMNM

Contact Info

Product

Resources

About

Necrosis in anti-SRP + and anti-HMGCR + myopathies

Abstract: These data further corroborate the pathogenic role of anti-SRP and anti-HMGCR autoantibodies in IMNM, highlighting humoral mechanisms as key players in immunity and myofiber necrosis.

Cited by 136 publications

References 29 publications

Anti-HMGCR Antibody–Related Necrotizing Autoimmune Myopathy Mimicking Muscular Dystrophy

Anti-HMGCR Antibody–Related Necrotizing Autoimmune Myopathy Mimicking Muscular Dystrophy

Autoimmune Myopathies: Updates on Evaluation and Treatment

CD163+ macrophage density in perimysial connective tissue associated with prognosis in IMNM

Contact Info

Product

Resources

About

Necrosis in anti-SRP ⁺ and anti-HMGCR ⁺ myopathies