scholarly journals Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013176
Author(s):  
Jantima Tanboon ◽  
Michio Inoue ◽  
Yoshihiko Saito ◽  
Hisateru Tachimori ◽  
Shinichiro Hayashi ◽  
...  
Keyword(s):  
Muscle Fiber ◽  
Inflammatory Myopathy ◽  
Protein A ◽  
Membrane Attack Complex ◽  
Muscle Pathology ◽  
Histological Features ◽  
Fiber Damage ◽  
Ultrastructural Studies ◽  
Perifascicular Atrophy ◽  
Muscle Biopsies

Background and Objectives:Discoveries of dermatomyositis specific antibodies (DMSAs) in dermatomyositis patients raised awareness of various myopathological features among antibody subtypes. However, only perifascicular atrophy and perifascicular myxovirus resistant protein A (MxA) overexpression were officially included as the definitive pathological criteria for dermatomyositis classification. We aimed to demonstrate myopathological features in MxA-positive dermatomyositis to determine characteristic myopathological features in different DMSA subtypes.Method:We performed a retrospective pathology review of muscle biopsies of dermatomyositis patients diagnosed between January 2009 and December 2020 in a tertiary laboratory for muscle diseases. We included all muscle biopsies with sarcoplasmic expression for MxA and seropositivity for DMSAs. MxA-positive muscle biopsies which tested negative for all DMSAs were included as seronegative dermatomyositis. We evaluated histological features stratified according to four pathology domains (muscle fiber, inflammatory, vascular, and connective tissue) and histological features of interest by histochemistry, enzyme histochemistry, and immunohistochemical study commonly used in the diagnosis of inflammatory myopathy. We performed ultrastructural studies of 54 available specimens.Result:A total of 256 patients were included. Of these, 249 patients were positive for one of the five DMSAs (seropositive patients: 87 anti-TIF1-γ; 40 anti-Mi-2; 29 anti-MDA5; 83 anti-NXP-2; and 10 anti-SAE DM) and 7 patients were negative for all five DMSAs (seronegative patients). Characteristic myopathological features in each DMSA subtype were as follows: anti-TIF1-γ with vacuolated/punched out fibers (64.7%, P<.001) and perifascicular enhancement in HLA-ABC stain (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 perimysial alkaline phosphatase activity (70.0%, P<.001), central necrotic peripheral regenerating fibers (45.0%, P<.001), and sarcolemmal membrane attack complex deposition (67.5%, P<.001); anti-MDA5 with scattered/diffuse staining pattern of MxA (65.5%, P<.001) with less muscle pathology and inflammatory features; 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).Discussion:We described a comprehensive serological-pathological correlation of DM primarily using MxA expression as an inclusion criterion. In our study, DMSAs were associated with distinctive myopathological features suggesting different underlying pathobiological mechanisms in each subtype.

scholarly journals Dermatomyositis: Muscle Pathology According to Antibody Subtypes

2021 ◽  
Author(s):  
Jantima Tanboon ◽  
Michio Inoue ◽  
Yoshihiko Saito ◽  
Shinichiro Hayashi ◽  
Satoru Noguchi ◽  
...  
Keyword(s):  
Muscle Fiber ◽  
Inflammatory Myopathy ◽  
Protein A ◽  
Membrane Attack Complex ◽  
Extensive Study ◽  
Muscle Pathology ◽  
Histological Features ◽  
Fiber Damage ◽  
Hla Dr ◽  
Perifascicular Atrophy

Abstract 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.

Pathological features of anti-Mi-2 dermatomyositis

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011269
Author(s):  
Jantima Tanboon ◽  
Michio Inoue ◽  
Shinya Hirakawa ◽  
Hisateru Tachimori ◽  
Shinichiro Hayashi ◽  
...  
Keyword(s):  
Muscle Fiber ◽  
Protein A ◽  
Membrane Attack Complex ◽  
Bonferroni Correction ◽  
Exact Test ◽  
Pathologic Features ◽  
Severity Scores ◽  
Complex Deposition ◽  
Muscle Biopsies

ObjectiveTo identify the characteristic pathologic features of dermatomyositis (DM) associated with anti-Mi-2 autoantibodies (anti-Mi-2 DM).MethodsWe reviewed 188 muscle biopsies from patients (1) pathologically diagnosed with DM through the sarcoplasmic expression for the myxovirus resistant protein A (MxA+) and (2) serologically positive for 1 of 5 DM-specific autoantibodies (DMSA) (anti-Mi-2, n = 30; other DMSA, n = 152) or negative for all 5 DMSAs (n = 6). We then compared the histopathologic and immunohistochemical features of anti-Mi-2 DM to non-Mi-2 DM and antisynthetase syndrome (ASS) patients (n = 212) using t-test, Fisher's exact test, and a logistic regression model.ResultsAnti-Mi-2 DM patients showed significantly higher severity scores in muscle fiber and inflammatory domains than non-Mi-2 DM patients. The presence of perifascicular necrosis, increased perimysial alkaline phosphatase activity, and sarcolemmal membrane attack complex deposition was more frequent in anti-Mi-2 DM patients (p < 0.01). Following Bonferroni correction, there were no significant differences in the percentages of the features mentioned above between the anti-Mi-2 DM and ASS (p > 0.01).ConclusionPerifascicular necrosis and perimysial pathology, features previously reported in ASS, are common in anti-Mi-2 DM patients. Our findings not only assist in differentiating anti-Mi-2 DM from other DM subtypes but also suggest the possibility of an overlapping mechanism between anti-Mi-2 DM and ASS.Classification of evidenceThis study provides Class II evidence that the muscle biopsies of DM patients with anti-Mi-2 autoantibodies are more likely to demonstrate higher severity scores in muscle fiber and inflammatory domains.

scholarly journals Muscle pathology in juvenile dermatomyositis

1997 ◽  
Vol 115 (5) ◽  
pp. 1555-1559 ◽  
Author(s):  
Edenilson Eduardo Calore ◽  
Maria José Cavaliere ◽  
Nilda Maria Perez
Keyword(s):  
Muscle Biopsy ◽  
Public Health Service ◽  
Vastus Lateralis ◽  
Inflammatory Myopathy ◽  
Muscle Pathology ◽  
Clinical Activity ◽  
Variable Intensity ◽  
Muscle Necrosis ◽  
One Year ◽  
Muscle Biopsies

OBJECTIVE: To study muscle biopsies, using histochemistry, on ten children with infantile dermatomyositis. DESIGN: Series of ten patients (of whom eight patients had received treatment and two had not) were submitted to muscle biopsy in order to diagnose possible inflammatory myopathy or to detect recurrences. PLACE OF DEVELOPMENT OF THE STUDY: Public Health Service of São Paulo State. PARTICIPANTS: children with clinical features of inflammatory myopathy. INTERVENTION: biopsies were performed on the vastus lateralis using local anesthetic. Histochemistry was performed according to standardized methods. RESULTS: Architectural changes of the muscle fibers, necrosis of variable intensity and accentuated evidence of regeneration were observed in patients who had not received treatment (2 cases) and in one case where muscular weakness persisted in spite of corticosteroid therapy. Necrosis and regeneration were minimal or absent in cases treated for one year or more (4 cases). In 3 cases with clinical and laboratorial recurrences, muscle necrosis and architectural changes were detected. CONCLUSIONS: It was concluded that muscle biopsy could aid in diagnosing infantile dermatomyositis as well as in detecting recurrences even in cases without clinical activity of the disease.

Coexistence of TDP-43 and C5b-9 staining of muscle in a patient with inclusion body myositis

2021 ◽  
Vol 14 (2) ◽  
pp. e238312
Author(s):  
Christina Law ◽  
Huili Li ◽  
Sankar Bandyopadhyay
Keyword(s):  
Inclusion Body ◽  
Transcriptional Repression ◽  
Inclusion Body Myositis ◽  
Inflammatory Myopathy ◽  
Membrane Attack Complex ◽  
Muscle Fibres ◽  
Rimmed Vacuoles ◽  
Histocompatibility Complex ◽  
Immune Mediated ◽  
Sporadic Inclusion Body Myositis

While sporadic inclusion body myositis (sIBM) is the most commonly acquired inflammatory myopathy above 50 years of age, its refractory response to conventional immunosuppressive treatments raises questions about its perplexing pathogenesis. Muscle biopsy typically reveals major histocompatibility complex I antigens and CD8+ T cell endomysial infiltrates invading non-necrotic muscle fibres early in the disease course with rimmed vacuoles, protein aggregates and amyloid inclusions later in the disease. Transactive response DNA-binding protein-43 (TDP-43), a protein implicated in transcriptional repression in neurodegenerative diseases, is also found in sIBM. C5b-9 membrane attack complex, an effector protein involved in the complement cascade of the immune response, is commonly found in dermatomyositis, but has rarely been reported in IBM. We describe a novel case of IBM with simultaneous C5b-9 and TDP-43 staining on quadriceps biopsy, raising the question of a possibility of concurrent immune-mediated inflammatory and myodegenerative pathogenesis.

scholarly journals INDIRECT VISUALIZATION OF STAPHYLOCOCCUS AUREUS PROTEIN A

1970 ◽  
Vol 131 (5) ◽  
pp. 1039-1047 ◽  
Author(s):  
D. Scott Nickerson ◽  
James G. White ◽  
Göran Kronvall ◽  
Ralph C. Williams ◽  
Paul G. Quie
Keyword(s):  
Cell Wall ◽  
Gamma Globulin ◽  
Protein A ◽  
Host Protein ◽  
Staphylococcal Protein A ◽  
Inflammatory Reactions ◽  
Host Environment ◽  
Outermost Layer ◽  
Bacterial Surface ◽  
Ultrastructural Studies

Specific but nonimmunologic reaction between staphylococcal protein A and the Fc portion of gamma globulin provided the basis for ultrastructural studies to determine the localization of protein A, using intact staphylococci and labeled myeloma gamma G-globulin. Protein A appeared to be part of the outermost layer of the staphylococcal cell wall. Strains with protein A demonstrated a coating of myeloma globulin over the entire bacterial surface. There was no coating of strains without protein A. Identification of protein A on the surface of the staphylococcal cell wall provides evidence that this may be the first material in contact with host environment. It probably accounts for apparent cross-reactions of staphylococci with antibodies to many antigens. More importantly, even in the nonimmune host protein A immunoglobulin reactivity may initiate complement activation and inflammatory reactions including chemotaxis and pus formation.

scholarly journals Clinical, genetic, and pathologic characterization of FKRP Mexican founder mutation c.1387A>G

2019 ◽  
Vol 5 (2) ◽  
pp. e315 ◽  
Author(s):  
Angela J. Lee ◽  
Karra A. Jones ◽  
Russell J. Butterfield ◽  
Mary O. Cox ◽  
Chamindra G. Konersman ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Founder Mutation ◽  
Congenital Muscular Dystrophy ◽  
Clinical Severity ◽  
Muscle Pathology ◽  
Clinical Genetic ◽  
End Stage ◽  
Muscle Biopsies ◽  
Normal Cognition

ObjectiveTo characterize the clinical phenotype, genetic origin, and muscle pathology of patients with the FKRP c.1387A>G mutation.MethodsStandardized clinical data were collected for all patients known to the authors with c.1387A>G mutations in FKRP. Muscle biopsies were reviewed and used for histopathology, immunostaining, Western blotting, and DNA extraction. Genetic analysis was performed on extracted DNA.ResultsWe report the clinical phenotypes of 6 patients homozygous for the c.1387A>G mutation in FKRP. Onset of symptoms was <2 years, and 5 of the 6 patients never learned to walk. Brain MRIs were normal. Cognition was normal to mildly impaired. Microarray analysis of 5 homozygous FKRP c.1387A>G patients revealed a 500-kb region of shared homozygosity at 19q13.32, including FKRP. All 4 muscle biopsies available for review showed end-stage dystrophic pathology, near absence of glycosylated α-dystroglycan (α-DG) by immunofluorescence, and reduced molecular weight of α-DG compared with controls and patients with homozygous FKRP c.826C>A limb-girdle muscular dystrophy.ConclusionsThe clinical features and muscle pathology in these newly reported patients homozygous for FKRP c.1387A>G confirm that this mutation causes congenital muscular dystrophy. The clinical severity might be explained by the greater reduction in α-DG glycosylation compared with that seen with the c.826C>A mutation. The shared region of homozygosity at 19q13.32 indicates that FKRP c.1387A>G is a founder mutation with an estimated age of 60 generations (∼1,200–1,500 years).

Histopathological features of the idiopathic inflammatory myopathies

2018 ◽  
Author(s):  
Marianne de Visser and Eleonora M.A. Aronica
Keyword(s):  
Inclusion Body ◽  
Muscle Biopsy ◽  
Inclusion Body Myositis ◽  
Inflammatory Myopathy ◽  
Adult Patients ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Histopathological Features ◽  
Muscle Biopsies

In adult patients with presumed idipathic inflammatory myopathy (IIM) without a characteristic and diagnostic dermatomyositis rash, muscle biopsy is mandatory to confirm the IIM diagnosis and to exclude a myopathy which would not respond to glucocorticoids or other immunosuppressants, including inclusion body myositis. This chapter discusses when, where, and how to undertake muscle biopsies, when to repeat them, how to interpret their results, and how these relate to IIM subtypes and disease processes.

Hypophysectomy mitigates skeletal muscle fiber damage in hamster dystrophy

1985 ◽  
Vol 17 (1) ◽  
pp. 60-64 ◽  
Author(s):  
G. Karpati ◽  
P. Jacob ◽  
S. Carpenter ◽  
S. Prescott
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Skeletal Muscle Fiber ◽  
Fiber Damage

scholarly journals Immunohistochemical markers of reactive skeletal muscle fibres

2019 ◽  
Vol 46 (s2) ◽  
pp. S67
Author(s):  
PV Gould
Keyword(s):  
Inflammatory Cell ◽  
Inflammatory Myopathy ◽  
Muscle Fibres ◽  
List Type ◽  
Routine Examination ◽  
Immunohistochemical Markers ◽  
Preliminary Study ◽  
Fibre Typing ◽  
Skeletal Muscle Fibres ◽  
Muscle Biopsies

Although most patients undergo muscle biopsies to elucidate the cause of muscle symptoms (weakess, cramping, etc.), many muscle biopsies show relatively few specific alterations on routine staining. Immunohistochemical methods for muscle fibre typing and characterisation of inflammatory cell infiltrates are now well established but the value of other markers is less well documented. A preliminary study of other potentially useful immunohistochemical markers revealed that muscle biopsies in our hospital often contain CD56 and/or D2-40 positive myofibres. This study was extended to a series of 32 biopsies from adult patients (age 21–81, 12 males 20 females), 11 of which showed only minor changes on routine examination. Most cases contained CD56 positive mature fibres; D2-40 positive muscle fibres were more common in cases of inflammatory myopathy. Five cases with minor changes on routine examination showed CD56 and D2-40 staining of otherwise unremarkable myofibres, which might represent reactive changes.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Describe patterns of immunohistochemical staining in reactive muscle fibres2.Discuss the underlying physiology of reactive muscle fibres

Childhood Dermatomyositis and Polymyositis

1984 ◽  
Vol 6 (6) ◽  
pp. 163-172
Author(s):  
Alfred J. Spiro
Keyword(s):  
Juvenile Dermatomyositis ◽  
Inflammatory Myopathy ◽  
Vascular Diseases ◽  
Epidemiologic Studies ◽  
Collagen Vascular Diseases ◽  
Pediatric Age Group ◽  
Adults And Children ◽  
Second Year ◽  
Muscle Biopsies ◽  
Childhood Dermatomyositis

Childhood dermatomyositis has been recognized as a clinicopathologic entity for approximately two decades. Polymyositis in the pediatric age group, as in adults, is not a singly defined entity, as it may occur with or without evidence of one of the collagen vascular diseases. Because of overlap of some features of both disorders the terms "polymyositis" and "polymyositis—dermatomyositis Complex" have sometimes been used to include both of these disorders. INCIDENCE Polymyositis and dermatomyositis are uncommon disorders; even in a referral center, there may be only two or three cases seen per year. The limited number of epidemiologic studies have included both adults and children and have combined several types of inflammatory myopathy. By this imperfect method, the annual incidence of new cases has varied from 1 to 7.7 per million persons. There is an increased incidence in the second and seventh decades of life, with a lower incidence in the third decade. Most reports of dermatomyositis have shown a preponderance of girls. Onset most commonly occurs at school age, but children in their second year of life have been affected. PATHOGENESIS Studies of muscle biopsies from patients with juvenile dermatomyositis have demonstrated that the basic lesion involves the endothelial cells of intramuscular capillaries, arterioles, and veins.

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