Skeletal Muscle Fibers Express Major Histocompatibility Complex Class II Antigens Independently of Inflammatory Infiltrates in Inflammatory Myopathies

Englund, Pernilla; Lindroos, Eva; Nennesmo, Inger; Klareskog, Lars; Lundberg, Ingrid E.

doi:10.1016/s0002-9440(10)62513-8

Cited by 129 publications

(108 citation statements)

References 33 publications

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“…The independence of MHC expression in muscle fibres from the presence of adjacent inflammatory cell infiltrates has also been noted in previous studies [15,[44][45][46][47]. This was observed in both the early and late chronic phases of the disease, and in symptomatic and asymptomatic muscles from the same individuals [48,49]. However, in the present study we found that, unlike MHC-I, there was a significant association between MHC-II expression and the presence of inflammatory infiltrates in the IIM group.…”

Section: Text 14supporting

confidence: 81%

An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies

Cruz

Luo

Miller

et al. 2014

Neuromuscular Disorders

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MURDOCH RESEARCH REPOSITORYThis is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Abstract 1 Abstract 3 AbstractAlthough there have been several previous reports of immunohistochemical staining for MHC antigens in muscle biopsies, there appears to be a lack of consensus about its routine use in the diagnostic evaluation of biopsies from patients with suspected inflammatory myopathy. Positive MHC-I staining is nonspecific but is widely used as a marker for inflammatory myopathy, while the role of MHC-II staining is not clearly defined. We investigated the sensitivity and specificity of MHC-I and II immunostaining for the diagnosis of inflammatory myopathy in a large group of biopsies from a single reference laboratory. Positive staining for MHC-I was found to have a high sensitivity in biopsies from patients with inflammatory myopathy but a very low specificity, as it was also common in other non-inflammatory myopathies and neurogenic disorders.On the other hand, MHC-II positivity had a much higher specificity in all major subgroups of inflammatory myopathy, especially inclusion body myositis. The findings indicate that the combination of MHC-I and MHC-II staining results in a higher degree of specificity for the diagnosis of inflammatory myopathy and that in biopsies with inflammation, positive MHC-II staining strongly supports the diagnosis of an immunemediated myopathy. We recommend that immunohistochemical staining for both MHC-I and MHC-II should be included routinely in the diagnostic evaluation of muscle biopsies from patients with suspected inflammatory myopathy. However, as the sensitivity and interpretation of MHC staining may depend on the technique used, further studies are needed to compare procedures in different centres and develop standardised protocols.Abstract 4

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Section: Text 14supporting

confidence: 81%

An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies

Cruz

Luo

Miller

et al. 2014

Neuromuscular Disorders

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“…Additionally, IFN-␥ and TNF may induce up-regulation of MHC class I or II Ags in muscle fibers which is a characteristic finding in patients with polymyositis or dermatomyositis but not in differentiated fibers from healthy individuals (43). Expression of MHC molecules on muscle fibers could allow T cell-muscle cell interaction, but this has been regarded unlikely because the costimulatory molecules CD80/86, normally required for functional interaction, are not expressed by inflamed muscle fibers (44,45). Still, T cells independent of costimulation by CD80/86, such as CD28 null T cells, could be activated following interaction with MHC-expressing muscle fibers and cause muscle fiber damage.…”

Section: Discussionmentioning

confidence: 99%

T Cell Infiltrates in the Muscles of Patients with Dermatomyositis and Polymyositis Are Dominated by CD28null T Cells

Fasth¹,

Dastmalchi²,

Rahbar

et al. 2009

The Journal of Immunology

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130

134

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Dermatomyositis and polymyositis are disabling rheumatic diseases characterized by an appreciable number of T cells infiltrating muscle tissue. The precise phenotype, function and specificity of these cells remain elusive. In this study, we aimed to characterize T cells in muscle tissue and circulation and to investigate their association to clinical phenotype. Twenty-four patients with dermatomyositis and 42 with polymyositis were screened for frequency of CD4+CD28null and CD8+CD28null T cells in peripheral blood by flow cytometry. Presence of these cells in inflamed muscle tissue from 13 of these patients was analyzed by three-color immunofluorescence microscopy. Effector functions, proliferation and Ag specificity were analyzed by flow cytometry after in vitro stimulation. The clinical relevance of CD28null T cells was analyzed by multiple regression analyses including six separate and combined disease variables. We demonstrate that muscle-infiltrating T cells are predominantly CD4+CD28null and CD8+CD28null T cells in patients with dermatomyositis and polymyositis. Muscle-infiltrating CD28null T cells were found already at time of diagnosis. Disease activity correlated with the frequency of CD8+ T cells in the inflamed muscles of polymyositis patients. Circulating CD4+CD28null and CD8+CD28null T cells were significantly more frequent in human CMV (HCMV) seropositive individuals, responded to HCMV Ag stimulation, and correlated with disease duration. These cells also display a proinflammatory cytokine profile, contain perforin and lack the costimulatory molecule CD28. Our observations imply that CD28null T cells represent clinically important effector cells in dermatomyositis and polymyositis, and that HCMV might play a role in propagating disease in a subset of patients.

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“…In most cases, the diagnosis of PM or DM was confirmed by typical histopathologic changes including inflammatory infiltrates in another biopsy specimen, by changes on electromyograms, or by the typical skin rash in DM (Table 1). Clinical data on some of these 14 patients have been presented previously (27). The median age at the time of biopsy was 46 years (range 26-61 years).…”

Section: Methodsmentioning

confidence: 99%

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

Grundtman¹,

Tham²,

Ulfgren³

et al. 2008

Arthritis & Rheumatism

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Objective. To investigate the expression of vascular endothelial growth factor (VEGF) in muscle biopsy specimens and serum from patients with polymyositis and patients with dermatomyositis compared with that in healthy control subjects.Methods. Muscle biopsy specimens from 33 patients with polymyositis or dermatomyositis and 15 healthy control subjects and serum samples from 56 patients and 56 healthy control subjects were analyzed. Patients were categorized into 3 groups, depending on disease duration and the presence or absence of inflammatory infiltrates. The expression of VEGF and the vessel marker CD31 in muscle was analyzed by immunohistochemistry, the expression of VEGF messenger RNA (mRNA) was analyzed by in situ hybridization, and serum levels of VEGF were determined by enzymelinked immunosorbent assay.Results. Patients with polymyositis or dermatomyositis in the early or chronic phase without inflammatory infiltrates had a decreased total number of capillaries compared with healthy individuals. In patients with early disease without inflammatory infil-

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Skeletal Muscle Fibers Express Major Histocompatibility Complex Class II Antigens Independently of Inflammatory Infiltrates in Inflammatory Myopathies

Cited by 129 publications

References 33 publications

An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies

An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies

T Cell Infiltrates in the Muscles of Patients with Dermatomyositis and Polymyositis Are Dominated by CD28null T Cells

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

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