Difference in adhesion molecule expression (ICAM-1 and VCAM-1) in juvenile and adult dermatomyositis, polymyositis and inclusion body myositis

doi:10.1016/j.autrev.2005.05.008

Autoimmunity Reviews

Volume 5, Issue 2, February 2006, Pages 93-100

https://doi.org/10.1016/j.autrev.2005.05.008 Get rights and content

Abstract

To assess the differential expression of adhesion molecules ICAM-1 and VCAM-1 in vessels and muscle fibers in acquired inflammatory myopathy, a series comprising thirty-seven muscle biopsy specimens from patients with JDM, fifteen with DM, fifteen with PM and seven with IBM was studied. Histochemical and immunohistochemical tests (StreptABCcomplex/HRP) for ICAM-1 and VCAM-1 (Dakopatts) were performed in serial frozen sections. ICAM-1 expression in vessels was significantly (p < 0.0001) more present in JDM than PM, DM or IBM. However, in muscle fibers, ICAM-1 expression was absent in both JDM and IBM, but present in 33.4% and 40% in PM and DM respectively (p < 0.0001). VCAM-1 expression in vessels was significantly more present in PM and DM than JDM and IBM (p < 0.0001) while VCAM-1 expression in muscle fibers was almost absent in the four groups (p = 0.2632). These findings emphasize the importance of adhesion molecules in the pathophysiology of the inflammatory myopathies, mainly the marked ICAM-1 expression in vessels in JDM, corroborating the microvascular involvement in this disease. In contrast, VCAM-1 seems not to play a major role in JDM, as previously described in PM, DM and IBM. Adhesion molecule expression in JDM presents a differential characteristic when compared to PM, DM and IBM.

Introduction

Distinct clinical, histological, and immunopathological characteristics allow classification of the acquired inflammatory myopathies into dermatomyositis, polymyositis and sporadic inclusion body myositis [1], [2], [3], [4], [5], [6]. Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in children, followed by far fewer cases of juvenile polymyositis, amyopathic dermatomyositis, overlap myositis and inclusion body myositis [1], [7], [8]. It is well known that JDM is characterized by marked vasculitis, more so than PM and DM [9], [10].

In JDM the most important target of immunopathologic attack has been shown to be the muscle blood vessels, particularly microvasculature, where deposits of immunoglobulin and activation of complement have been reported [11], [12], [13], [14].

Moreover, there is a body of evidence pointing to microangiopathy and muscle ischemia in DM, whereas an antigen-directed cytotoxicity mediated by a cytotoxic T cells mechanism leads to skeletal muscle damage in PM and IBM [15], [16]. This immunopathogenic mechanism involving antigen-specific cytotoxic T cells is a restricted MHC class I-dependent process [17]. Additionally, MHC-I and -II dependent processes require expression of ICAM-1, which is necessary to stabilize the interactions between the cell receptor and MHC-peptide complex in antigen recognition [18].

In this context, the expression analysis of these adhesion molecules could be of value to further the understanding of differences in the pathomechanisms of the acquired inflammatory myopathies.

Section snippets

Patients and methods

Thirty-seven muscle biopsy specimens from patients fulfilling Bohan and Peter definite criteria for JDM [1], [10], fifteen for DM, fifteen for PM, and seven for IBM, and attending the Pediatric and Rheumatology Units—University of São Paulo Medical School and Santa Casa de Misericórdia de São Paulo Medical School, were studied.

Prior to the muscle biopsy, the patients were informed of the objectives of the examination and their written consent was obtained. The study was approved by the local

Results

ICAM-1 expression in vessels was more evident (p < 0.0001) in JDM than PM, DM and IBM. On the other hand, in muscle fibers, ICAM-1 expression was absent in JDM and IBM, but present in 33.4% and 40% respectively of PM and DM (p < 0.0001). VCAM-1 expression in vessels was more significant for PM and DM than JDM and IBM (p < 0.0001) and VCAM-1 expression in muscle fibers was virtually absent in the four groups (p = 0.2632) (Fig. 1; Table 1, Table 2).

Discussion

In the present study, we demonstrated that ICAM-1 expression in muscle vessels was more evident for JDM, than for DM, PM and IBM, corroborating the microvascular involvement in JDM.

In our previous study we had demonstrated an increased ICAM-1 expression in intramuscular vessels, markedly in capillaries, in contrast to a less striking VCAM-1 expression in the same muscle vessels of patients with JDM, compared with normal age-matched muscle biopsies [14]. An increased expression of ICAM-1 has

References (30)

L.R. Wedderburn et al.
Paediatric idiopathic inflammatory muscle disease
Best Pract Res Clin Rheumatol
(2004)
S. Compeyrot-Lacassagne et al.
Inflammatory myopathies in children
Pediatr Clin North Am
(2005)
L.M. Pachman et al.
Juvenile dermatomyositis: a clinical and immunologic study
J Pediatr
(1980)
R. Estruch et al.
Microvascular changes in skeletal muscle in idiopathic inflammatory myopathy
Hum Pathol
(1992)
A. Bohan et al.
Polymyositis and dermatomyositis
N Engl J Med
(1975)
M.C. Dalakas
Molecular immunology and genetics of inflammatory muscle diseases
Arch Neurol
(1998)
I.E. Lundberg
Idiopathic inflammatory myopathies: why do the muscles become weak?
Curr Opin Rheumatol
(2001)
M. Civatte et al.
Class I MHC detection as a diagnostic tool in noninformative muscle biopsies of patients suffering from dermatomyositis (DM)
Neuropathol Appl Neurobiol
(2003)
K. Arahata et al.
Monoclonal antibody analysis of mononuclear cells in myopathies: I. Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells
Ann Neurol
(1984)
M.C. Dalakas et al.
The immunopathologic and inflammatory differences between dermatomyositis, polymyositis and sporadic inclusion body myositis
Curr Opin Neurol
(1996)

L. Rider

Childhood myositis: newly recognized diversity

A.M.E Sallum et al.

Juvenile dermatomyositis: clinical, laboratorial, histological, therapeutical and evolutive parameters of 35 patients

Arq Neuropsiquiatr

(2002)

F.G. Gonçalves et al.

Immunohistochemical analysis of CD59 and membrane attack complex of complement in muscle in juvenile dermatomyositis

J Rheumatol

(2002)

A.M.E. Sallum et al.

Immunohistochemical analysis of adhesion molecule expression on muscle biopsy specimens from patients with juvenile dermatomyositis

J Rheumatol

(2004)

E. Bartoccioni et al.

MHC class I, MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression in inflammatory myopathies

Clin Exp Immunol

(1994)

Cited by (43)

Ocular microvascular damage in autoimmune rheumatic diseases: The pathophysiological role of the immune system
2021, Autoimmunity Reviews
Citation Excerpt :
There are however other several mechanisms of endothelial dysfunction being explored in IIMs. [126] Firstly, an enhanced expression of adhesion molecules has been reported, particularly in JDM where intercellular adhesion molecule 1 (ICAM-1) vessel expression was shown to be higher compared with adult DM and PM (Fig. 2C) [127]. Deposits of C5b-C9 and membrane attack complex (MAC) have been also detected in DM patients suggesting an activation of the complement cascade with a subsequent pro-inflammatory milieu of cytokines, chemokines and facilitation of leukocytes transmigration (Fig. 2C) [128].
Pathological eye involvement represents a quite common finding in a broad spectrum of autoimmune rheumatic diseases (ARDs). Ocular signs, often occur as early manifestations in ARDs, ranging from symptoms related to the mild dry eye disease to sight-threatening pathologies, linked to the immune response against retinal and choroidal vessels. Retinovascular damage driven by markedly inflammatory reactivity need a prompt diagnosis and treatment.
Immune-complexes formation, complement activation and antibody-mediated endothelial damage seem to play a key role, particularly, in microvascular damage and ocular symptoms, occurring in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS).
Conversely, early alterations of retinal and choroidal vessels in the asymptomatic patient, often detectable coincidentally, might be indicators of widespread vascular injury in other connective tissue diseases. Particularly, endothelin-induced hypoperfusion and pathological peri-choroidal extracellular matrix deposition, might be responsible for the micro-architectural alterations and loss of capillaries detected in systemic sclerosis (SSc). Instead, interferon alpha-mediated microvascular rarefaction, combined with endothelial lesions caused by specific autoantibodies and immune-complexes, appear to play a significant role in retinal vasculopathy associated to inflammatory idiopathic myopathies (IIM).
The immuno-pathophysiological mechanisms of ocular microcirculatory damage associated with the major ARDs will be discussed under the light of the most recent achievements.
Skeletal muscle cells actively shape (auto)immune responses
2018, Autoimmunity Reviews
Citation Excerpt :
Adhesion molecules such as ICAM-1 and the corresponding ligand lymphocyte function-associated antigen 1 (LFA-1) are essential in the formation of the immunological synapse to ensure TCR-MHC-interactions [63]. The expression of ICAM-1 has been demonstrated on cultured SkMCs under pro-inflammatory conditions and on myofibers from IIM patients [64–70] (Fig. 2). Membrane bound ICAM-1 is upregulated on cultured SkMCs upon incubation with a number of pro-inflammatory cytokines such as IFN-γ, IL-1β, IL-4 and IL-6 [65,68,69,71].
Histopathological analyses of muscle specimens from myositis patients indicate that skeletal muscle cells play an active role in the interaction with immune cells. Research over the last few decades has shown that skeletal muscle cells exhibit immunobiological properties that perfectly define them as non-professional antigen presenting cells. They are able to present antigens via major histocompatibility complex molecules, exhibit costimulatory molecules and secrete soluble molecules that actively shape the immune response in an either pro- or anti-inflammatory manner. Skeletal muscle cells regulate both innate and adaptive immune responses and are essentially involved in the pathophysiological processes of idiopathic inflammatory myopathies. Understanding the role of skeletal muscle cells might help to identify new therapeutic targets for these devastating diseases. This review summarizes the immunobiological features of skeletal muscle cells, especially in the context of idiopathic inflammatory myopathies, and discusses shortcomings and limitations in skeletal muscle related research providing potential perspectives to overcome them in the future.
Juvenile Dermatomyositis
2015, Textbook of Pediatric Rheumatology
Idiopathic inflammatory myopathies
2014, Handbook of Clinical Neurology
Citation Excerpt :
Muscle cells actively participate in these immune reactions by expressing MHC-I antigens and costimulatory molecules on their sarcolemma (Bartoccioni et al., 1994). Blood vessel endothelial cells selectively recruit leukocytes, through upregulation of anchor proteins such as the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (De Bleecker and Engel, 1994; Sallum et al., 2006) allowing their transmigration from the circulation into the muscle tissue. Whether sIBM is a primary inflammatory myopathy, like DM and PM, or a myopathy in which the inflammatory response plays a secondary role, is the subject of intense research (Griggs et al., 1995).
Idiopathic inflammatory myopathies (IIMs), except for sporadic inclusion body myositis (sIBM), present with subacute symmetrical weakness of the limb girdle muscles, an elevated serum creatine kinase activity, and inflammatory cells in the muscle biopsy (necrotizing autoimmune myopathy being an exception). In dermatomyositis, additional skin abnormalities are found. IIMs are nowadays subclassified into the following categories: (1) dermatomyositis (DM), including (1a) classic dermatomyositis, which may be associated with connective tissue disorders (CTDs) and malignancy, (1b) juvenile dermatomyositis, and (1c) clinical amyopathic dermatomyositis; (2) polymyositis (PM) encompassing (2a) classical PM and (2b) nonspecific or overlap myositis, associated with CTD; (3) autoimmune necrotizing myopathy, associated with malignancy, statin use and CTD; and (4) sporadic IBM, sometimes associated with CTDs. These conditions result from chronic immune activation after exposure to environmental risk factors in individuals with a predisposing genetic background.
A strong association of autoantibodies with distinct clinical phenotypes and prognosis is found in patients with myositis.
Inflammatory myopathies, sporadic IBM excluded, are amenable to immunosuppressive and immunomodulation therapies. The prognosis of IIM is not well known since long-term outcome and prognostic factors vary widely. Disease-related mortality rates in PM and DM are at least 10%. In DM mortality is attributed to cancer and pulmonary complications. Juvenile dermatomyositis has a low mortality rate. Because chronic immunosuppressive therapy is associated with significant side-effects, and many patients remain (partially) refractory to treatment, novel therapeutic agents that are safe and effective are needed.
Actuality of juvenile dermatomyositis
2011, Joint Bone Spine
Citation Excerpt :
This is a different pathological process from that of the polymyositis, during which the myofibrils are directly subject to cytotoxic autoreactive CD8+ T-lymphocytes. Other particularities have been observed in JDM, such as preferential expression of ICAM-1 type adhesion molecules by the muscular vessels [19]. In JDM, the clinical picture is, to a certain degree, more insidious and systemic than in the adult form.
Juvenile dermatomyositis is a rare disorder, but remains the most commonly occurring chronic inflammatory myopathy among children. Other than the proximal muscles and skin, which are routinely affected, vasculopathy may affect other viscera and can be multisystemic. A redefinition of the diagnostic criteria is currently underway and is likely to lead to other clinical signs and to sensitive and non-invasive examinations such as MRI. The impact of juvenile dermatomyositis on health and quality of life remains significant despite systemic corticosteroid therapy and immunosuppressor treatment, which have considerably improved the prognosis. Numerous predictors for favourable and pejorative evolution have been identified. The standardisation and the generalisation of clinical assessment tools will make it possible to carry out the clinical trials required to determine the relevance of the new therapeutic options available for children.
Updates on juvenile dermatomyositis
2011, Revue du Rhumatisme (Edition Francaise)
La dermatomyosite juvénile est une affection rare, qui reste la plus fréquente des myopathies inflammatoires chroniques de l’enfant. Outre la peau et les muscles proximaux dont les atteintes sont caractéristiques, la vasculopathie peut intéresser d’autres viscères et être multi-systémique. Une redéfinition des critères diagnostiques est en cours, appelés à s’élargir à d’autres manifestations cliniques et à des examens sensibles et non invasifs comme l’IRM. Le retentissement de la dermatomyosite juvénile sur l’état de santé et sur la qualité de vie demeure considérable malgré la corticothérapie systémique et les immunosuppresseurs, qui en ont sensiblement amélioré le pronostic. Nombreux éléments prédictifs d’évolution favorable ou péjorative ont été identifiés. La standardisation et la généralisation des outils d’évaluation clinique permettront de conduire les essais cliniques nécessaires pour situer la place des nouvelles options thérapeutiques chez l’enfant.

View all citing articles on Scopus

^☆: Grant from FAPESP 98/16290-6.

View full text

Difference in adhesion molecule expression (ICAM-1 and VCAM-1) in juvenile and adult dermatomyositis, polymyositis and inclusion body myositis☆

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Best Pract Res Clin Rheumatol

Pediatr Clin North Am

J Pediatr

Hum Pathol

Polymyositis and dermatomyositis

N Engl J Med

Molecular immunology and genetics of inflammatory muscle diseases

Arch Neurol

Idiopathic inflammatory myopathies: why do the muscles become weak?

Curr Opin Rheumatol

Class I MHC detection as a diagnostic tool in noninformative muscle biopsies of patients suffering from dermatomyositis (DM)

Neuropathol Appl Neurobiol

Monoclonal antibody analysis of mononuclear cells in myopathies: I. Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells

Ann Neurol

The immunopathologic and inflammatory differences between dermatomyositis, polymyositis and sporadic inclusion body myositis

Curr Opin Neurol

Childhood myositis: newly recognized diversity

Juvenile dermatomyositis: clinical, laboratorial, histological, therapeutical and evolutive parameters of 35 patients

Arq Neuropsiquiatr

Immunohistochemical analysis of CD59 and membrane attack complex of complement in muscle in juvenile dermatomyositis

J Rheumatol

Immunohistochemical analysis of adhesion molecule expression on muscle biopsy specimens from patients with juvenile dermatomyositis

J Rheumatol

MHC class I, MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression in inflammatory myopathies

Clin Exp Immunol