Polymyositis and dermatomyositis. (2003 Sep)
polymyositis and dermatomyositis . The inflammatory myopathies , commonly described as idiopathic , are the largest group of acquired and potentially treatable myopathies . On the basis of unique clinical , histopathological , immunological , and demographic features , they can be differentiated into three major and distinct subsets : dermatomyositis , polymyositis , and inclusion body myositis . Use of new diagnostic criteria is essential to discriminate between them and to exclude other disorders . dermatomyositis is a microangiopathy affecting skin and muscle ; activation and deposition of complement causes lysis of endomysial capillaries and muscle ischaemia . In polymyositis and inclusion body myositis , clonally expanded CD8 positive cytotoxic T cells invade muscle fibres that express MHC class I antigens , which leads to fibre necrosis via the perforin pathway . In inclusion body myositis , vacuolar formation with amyloid deposits coexists with the immunological features . The causative autoantigen has not yet been identified . upregulated vascular cell adhesion molecule , intercellular adhesion molecule , chemokines , and their receptors promote T cell transgression , and various cytokines increase the immunopathological process . early initiation of therapy is essential , since both polymyositis and dermatomyositis respond to immunotherapeutic agents . New immunomodulatory agents currently being tested in controlled trials may prove promising for difficult cases .

Expression of adhesion molecules in idiopathic inflammatory myopathies. (1999 Jun)
expression of adhesion molecules in idiopathic inflammatory myopathies . immunohistochemical study of 17 cases We investigated the immunohistochemical expression of endothelial cell adhesion molecules in 17 cases of idiopathic inflammatory myopathies . The present study revealed : 1 ) a constitutive expression of ICAM 1 , ICAM 2 and pecam 1 , but not VCAM 1 , LFA 3 and E selectin , on endothelial cells in normal muscles ; 2 ) a modification of cell adhesion molecules expression in idiopathic inflammatory myopathies with an increased expression of the expressed molecules constitutively ; an expression of LFA 3 and VCAM 1 on capillary endothelial cells in polymyositis / inclusion body myositis , these molecules being only observed on endothelial cells of some arterioles in dermatomyositis ; 3 ) an expression of all these molecules on inflammatory cells in inflammatory myopathies . In dermatomyositis , the expression of ICAM 1 and VCAM 1 , predominated on mononuclear cells located near vessels . In polymyositis / inclusion body myositis , a strong expression of ICAM 1 , VCAM 1 and LFA 3 was present on inflammatory cells invading non necrotic muscle fibers ; 4 ) absence of E selectin on endothelial and inflammatory cells in all cases .

A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli. (1998 Sep)
A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli . muscle is an attractive target for gene therapy and for immunization with DNA vaccines and is also the target of immunological injury in myositis . It is important therefore to understand the immunologic capabilities of muscle cells themselves . In this study , we show that proinflammatory stimuli induce the expression of other cytokines such as IL 6 , transforming growth factor beta ( TGF beta ) , and granulocyte macrophage colony stimulating factor ( GM CSF ) by muscle cells themselves , as well as the up regulation of human leucocyte antigen ( HLA ) class I , class II and intercellular adhesion molecule 1 ( ICAM 1 ) . Thus , muscle cells have an inherent ability to express and respond to a variety of cytokines and chemokines . The levels of HLA class I , class II and ICAM 1 in inflamed muscle may be affected by the secreted products of the stimulation .

Expression of cell adhesion molecules in inflammatory myopathies and duchenne dystrophy. (1994 Aug)
expression of cell adhesion molecules in inflammatory myopathies and duchenne dystrophy . Cell adhesion molecules participate in target effector cell interactions in cell mediated cytotoxicity and in leukodiapedesis in inflammatory diseases . Two ligand receptor pairs may play a role in the adhesion of cytotoxic T cells to their targets : 1 ) intercellular adhesion molecule 1 ( ICAM 1 ) and lymphocyte function associated antigen 1 ( LFA 1 ) , and 2 ) LFA 3 and CD2 . We therefore immunolocalized these molecules in myopathies where there is evidence for T cell mediated myocytotoxicity , namely inclusion body myositis , polymyositis , and duchenne dystrophy . autoaggressive inflammatory cells close to invaded muscle fibers showed an increased expression of ICAM 1 and LFA 1 . The nonnecrotic muscle fibers invaded by autoaggressive cells expressed ICAM 1 where their surfaces faced the invading cells . That immunoreactivity for ICAM 1 on the invading cells was distinct from that on the opposite muscle fiber surface was established by colocalization of ICAM 1 with the sarcolemmal marker dystrophin ( or beta spectrin ) and was also confirmed by confocal microscopy . leukodiapedesis in inflamed tissues is mediated by ICAM 1 , LFA 3 , vascular cell adhesion molecule 1 ( VCAM 1 ) , and E selectin associated with endothelial cells . In dermatomyositis ICAM 1 was strongly expressed on endothelial cells of perimysial arterioles and venules and on some perifascicular capillaries . In all the other myopathies ICAM 1 and …

Decreased expression of interleukin 1alpha , interleukin 1beta , and cell adhesion molecules in muscle tissue following corticosteroid treatment in … (2000 Mar)
decreased expression of interleukin 1alpha , interleukin 1beta , and cell adhesion molecules in muscle tissue following corticosteroid treatment in patients with polymyositis and dermatomyositis . objective : To study the effects of immunosuppressive therapy , in particular , corticosteroids , on morphologic signs of inflammation and expression of cytokines , adhesion molecules , and class I major histocompatibility complex ( MHC ) antigen in muscle tissue from patients with polymyositis ( PM ) and dermatomyositis ( DM ) and to correlate the molecular changes with changes in muscle function . methods : seven patients with PM and 4 patients with DM underwent muscle biopsy before and after 3 6 months of therapy . Ten of the 11 patients were initially treated with prednisolone 30 60 mg / day . The phenotypes of infiltrating inflammatory cells and the expression of interleukin 1alpha ( IL 1alpha ) and IL 1beta , adhesion molecules , and class I MHC antigen were studied by immunochemistry . computerized image analysis was used for quantitation of staining . muscle function was assessed with a muscle function index score . results : pronounced improvement of muscle function during the treatment period was noted in 8 of the 11 patients . The changes in muscle function coincided with an almost complete disappearance of inflammatory cells , including CD3 T cells , in the patients with clinical improvement . these patients also exhibited decreased expression of IL 1alpha , IL 1beta , intercellular adhesion molecule 1 ( ICAM …

Leucocyte / endothelial cell adhesion receptors in muscle biopsies from patients with idiopathic inflammatory myopathies ( IIM ). (1997 May)
leucocyte / endothelial cell adhesion receptors in muscle biopsies from patients with idiopathic inflammatory myopathies ( IIM ) . interactions between leucocytes and endothelial cells through specific adhesion receptors play an increasingly recognized crucial role in the development of inflammatory infiltrates in chronic inflammatory diseases . In this study we investigated adhesion molecule expression in muscle biopsies from 18 dermatomyositis , six polymyositis , five inclusion body myositis patients and from eight normal controls . immunohistochemical detection of leucocyte integrins LFA 1 and VLA 4 , their endothelial counter receptors intercellular adhesion molecule 1 ( ICAM 1 ) and vascular cell adhesion molecule 1 ( VCAM 1 ) , and the endothelial cell markers CD31 and von willebrand factor related antigen ( vwfag ) was performed using specific moabs and an alkaline phosphatase anti alkaline phosphatase technique . ICAM 1 expression was up regulated and VCAM 1 induced in muscle capillaries of dermatomyositis samples . In both dermatomyositis and polymyositis , endothelial cells from vessels surrounded by inflammatory infiltrates strongly expressed ICAM 1 and VCAM 1 . infiltrating leucocytes were intensively LFA 1 and VLA 4 positive . these data suggest that leucocyte / endothelial cell interactions mediated by the receptor / ligand pairs LFA 1 / ICAM 1 and VLA 4 / VCAM 1 actively participate in the development of muscle inflammatory infiltrates in the major inflammatory myopathies . In addition , ICAM 1 and VCAM 1 over expression by capillary endothelial cells in dermatomyositis supports the hypothesis that …

The role of cytokines in polymyositis. (1994 Jul)
The role of cytokines in polymyositis . III . recombinant human interferon gamma enhances T cell adhesion to cultured human muscle cells . objective : To investigate the effect of interferon gamma ( IFN gamma ) on the adhesive interactions between human peripheral blood T cells and human skeletal muscle cells at various stages of muscle cell differentiation and maturation in vitro . methods : human muscle cell cultures were established from normal muscle biopsy material , using the explant technique . T cells were studied for their capacity to adhere to IFN gamma treated and untreated myoblasts and myotubes . The role of intercellular adhesion molecule type 1 ( ICAM 1 ) in cell adhesion to muscle cells was examined in blocking studies , by enzyme linked immunosorbent assay ( elisa ) , and by immunohistochemical staining using monoclonal antibodies ( MAb ) . results : treatment of muscle cells ( myoblasts and myotubes ) with IFN gamma resulted in a significant dose dependent increase in the number of adherent T cells . adhesion of T cells to muscle cells was significantly inhibited by MAb to ICAM 1 and to lymphocyte function associated antigen type 1 , but not by MAb to HLA DR . there was no difference in the level of T cell adhesion to IFN gamma treated allogeneic versus autologous muscle cells . By elisa and immunohistochemical analysis , ICAM 1 expression on the surface of cultured human muscle cells was either absent or barely detectable …

Limited effects of high dose intravenous immunoglobulin ( IVIG ) treatment on molecular expression in muscle tissue of patients with … (2007 Sep)
limited effects of high dose intravenous immunoglobulin ( IVIG ) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies . objectives : The study was conducted with the aim of achieving an improved understanding of the molecular mechanisms of high dose intravenous immunoglobulin ( IVIG ) in inflammatory myopathies by investigating the effects on muscle function and immunological molecules in skeletal muscle of polymyositis ( PM ) , dermatomyositis ( DM ) and inclusion body myositis ( IBM ) patients . methods : thirteen treatment resistant patients , 6 PM , 4 DM , 2 IBM and 1 juvenile DM , were treated with 2 g / kg of IVIG , three times at monthly intervals . functional index in myositis and serum creatinine kinase ( CK ) levels were determined , and muscle biopsies were performed before treatment and after the third IVIG infusion . immunological molecules were also studied in biopsies taken 24 48 h after the first infusion . results : improved muscle function was observed in three patients ( 1 PM , 1 DM and 1 IBM ) and CK levels decreased in five . T cells , macrophages , major histocompatibility complex ( MHC ) class I antigen on muscle fibres , intercellular adhesion molecule 1 ( ICAM 1 ) and vascular cell adhesion molecule 1 ( VCAM 1 ) expression and membranolytic attack complex ( MAC ) deposits on capillaries were present to an equal degree in biopsies before and after …

Difference in adhesion molecule expression ( ICAM 1 and VCAM 1 ) in juvenile and adult dermatomyositis , polymyositis and … (2006 Jan)
difference in adhesion molecule expression ( ICAM 1 and VCAM 1 ) in juvenile and adult dermatomyositis , polymyositis and inclusion body myositis . 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 …

Peripheral lymphoid tissue like adhesion molecule expression in nodular infiltrates in inflammatory myopathies. (1997 Feb)
peripheral lymphoid tissue like adhesion molecule expression in nodular infiltrates in inflammatory myopathies . Non granulomatous nodular accumulations of inflammatory cells in inflammatory myopathies were studied to characterize adhesion mechanisms used for leukocyte recruitment . The nodules had a B cell rich center surrounded by a helper T cell rich peripheral zone , resembling lymph nodes . The T cell rich zones harbored high walled venules resembling high endothelial venules ( HEV ) , whose endothelia frequently expressed ICAM 1 , VCAM 1 , and less constantly E selectin . This endothelial adhesion molecule profile differs from that found in polymyositis , inclusion body myositis , or dermatomyositis , but resembles that in lymphoid tissues . Also , the peripheral lymph node addressin , a vascular addressin specific for peripheral lymphoid tissue HEV , was present on many HEV . This adhesion system is probably responsible for the excessive lymphocyte recruitment . The similar cellular organization and lymphocyte recirculation mechanisms of the nodular infiltrates in muscle and of lymph nodes suggest that the former may also produce antibodies .

MHC class I , MHC class II and intercellular adhesion molecule 1 ( ICAM 1 ) expression in inflammatory myopathies. (1994 Feb)
MHC class I , MHC class II and intercellular adhesion molecule 1 ( ICAM 1 ) expression in inflammatory myopathies . We investigated the relationship between the MHC I , MHC II and intercellular adhesion molecule 1 ( ICAM 1 ) expression on myofibres and the presence of inflammatory cells in muscle specimens of 18 patients with inflammatory myopathies ( nine polymyositis , seven dermatomyositis , two inclusion body myositis ) . We observed MHC I expression in muscle fibres , infiltrating mononuclear cells and endothelial cells in every specimen . In seven patients , some muscle fibres were MHC II positive for the DR antigen , while the DP and DQ antigens were absent . ICAM 1 expression , detected in seven patients , was found in clusters of myofibres , associated with a marked MHC I positivity and a widespread mononuclear infiltration . Most of the ICAM 1 positive fibres were regenerating fibres . furthermore , some fibres expressed both ICAM 1 and DR antigens near infiltrating cells . This finding could support the hypothesis that myofibres may themselves be the site of autosensitization .

Fk506 suppressed the inflammatory change of EAM in SJL / J mice. (2001 Nov)
fk506 suppressed the inflammatory change of EAM in SJL / J mice . experimental autoimmune myositis ( EAM ) is a good model of human inflammatory myopathy . We induced EAM in SJL / J mice by injection with myosin and treated inflammatory changes with fk506 . The mice developed inflammatory changes after the fifth myosin injection . after treatment with fk506 , inflammation was suppressed and central nuclei of the muscle fibers increased . these findings indicate that fk506 is effective in the treatment of EAM . The data suggests that fk506 inhibits interaction with calcineurin . intercellular adhesion molecule 1 ( ICAM 1 ) positive cells were present in the inflammatory and non inflammatory areas of EAM . The fk506 treated group stained more weakly for ICAM 1 than the untreated EAM group .

Adhesion molecule expression in experimental myositis. (2002 Feb)
adhesion molecule expression in experimental myositis . experimental allergic myositis ( EAM ) in lewis rats , induced with partially purified myosin , is regarded as a model of human polymyositis . To clarify the role of adhesion molecules in the pathogenesis of EAM in lewis rats , we investigated intramysial expressions of the intercellular adhesion molecule ( ICAM ) 1 and vascular cell adhesion molecule ( VCAM ) 1 , and the serum level of soluble ICAM 1 in EAM rats . All the EAM rat muscles had scattered inflammatory foci , as well as cell infiltration and necrosis , by week 4 after the initial immunization ( i . e . , day 0 after the last immunization ) . As compared with the control muscles , ICAM 1 and VCAM 1 were strongly expressed immunohistochemically in the endothelium of vessels in the endomysium and perimysium , and to lesser extents in the inflammatory infiltrates and on the sarcolemma of nonnecrotic muscle fibers adjacent to the inflammatory infiltrates or invaded muscle fibers . ICAM 1 in the muscle extracts and sera from EAM rats increased on each test day , as compared with extracts from the normal controls . The values peaked on day 0 after the last immunization , then gradually decreased with time . ICAM 1 elevations in the muscle extracts were correlated with the percent of sections that had inflammatory lesions ( P 0 . 032 ) and the histological scores ( P 0 . …

Interleukin 1alpha expression in capillaries and major histocompatibility complex class I expression in type II muscle fibers from polymyositis and … (2002 Apr)
interleukin 1alpha expression in capillaries and major histocompatibility complex class I expression in type II muscle fibers from polymyositis and dermatomyositis patients : important pathogenic features independent of inflammatory cell clusters in muscle tissue . objective : To address the hypothesis that endothelial cells and / or muscle fibers are primary targets in the disease process by analysis of muscle tissue from patients with polymyositis ( PM ) and dermatomyositis ( DM ) . methods : We included patients with laboratory signs and clinical symptoms typical of myositis , but without detectable infiltration of clusters of inflammatory cells in their muscle biopsy samples . An immunohistochemical technique was applied to identify CD3 , CD68 , lymphocyte function associated antigen 1alpha , cd11b , very late activation antigen 4 , endothelium 4 , interleukin 1alpha ( IL 1alpha ) , intercellular adhesion molecule 1 , vascular cell adhesion molecule 1 , IgG , IgM , IgA , and HLA A / B / C in muscle tissue . fiber type was defined by atpase staining . results : IL 1alpha expression was detected in endothelial cells of capillaries to a greater extent in patients than in controls , and class I major histocompatibility complex ( MHC ) expression was significantly increased in muscle fibers . We also observed that class I MHC expression was mainly confined to type II muscle fibers . conclusion : Our findings imply that defined molecular changes of blood vessels and muscle fibers are both independent of …

Interleukin 17 increases the effects of IL 1 beta on muscle cells : arguments for the role of T cells … (2003 Apr)
interleukin 17 increases the effects of IL 1 beta on muscle cells : arguments for the role of T cells in the pathogenesis of myositis . We studied the production of interleukin ( IL ) 6 and ccl20 / macrophage inflammatory protein 3 alpha ( MIP 3 alpha ) by human myoblasts and muscle samples in response to IL 17 alone or in combination with IL 1 beta . Both IL 17 and IL 1 beta induced IL 6 production by normal myoblasts and muscle samples . IL 17 had no effect on ccl20 production by myoblasts . combination of IL 17 and IL 1 beta further increased IL 6 and ccl20 production by muscle samples but not that of CK . IL 17 induced also HLA class I , C Fos , nuclear factor kappa B ( NF kappa B ) and C Jun expression by myoblasts but not that of HLA class II , CD40 , vascular cell adhesion molecule 1 ( VCAM 1 ) and intercellular adhesion molecule 1 ( ICAM 1 ) . finally , immunostaining of dermatomyositis ( DM ) and polymyositis ( PM ) muscle biopsies showed IL 17 and ccl20 expression . Our study shows that low levels of cytokines produced by T cells ( IL 17 ) and monocytes ( IL 1 beta ) can act in combination on skeletal myoblasts and muscle tissue .

Platelet endothelial cell adhesion molecule 1 and cd146 : soluble levels and in situ expression of cellular adhesion molecules implicated … (2006 Aug)
platelet endothelial cell adhesion molecule 1 and cd146 : soluble levels and in situ expression of cellular adhesion molecules implicated in the cohesion of endothelial cells in idiopathic inflammatory myopathies . objective : idiopathic inflammatory myopathies ( IIM ) are a heterogeneous group of diseases characterized by chronic inflammation of muscles . We investigated the role of cellular adhesion molecules implicated in the cohesion of endothelial cells in IIM . methods : In 22 patients with IIM we investigated plasma concentrations of soluble junctional adhesion molecules platelet endothelial cell adhesion molecule ( specam 1 ) and scd146 and cellular adhesion molecules sP selectin , sE selectin , intercellular adhesion molecule ( sicam 1 ) , and vascular cell adhesion molecule ( svcam 1 ) implicated in leukocyte / endothelial cell interactions . results were compared to a control group . muscle biopsy samples from 8 out of 22 IIM patients were studied by immunohistochemistry for tissue expression of these molecules and compared to normal muscle samples . pecam 1 and cd146 expression was also studied using immunoblots from muscle biopsies from 5 patients and 2 controls . results : We observed distinct patterns of soluble levels and in situ expression between dermatomyositis ( DM ) , polymyositis ( PM ) , and sporadic inclusion body myositis ( s IBM ) . PM samples showed significantly increased levels of scd146 , specam 1 , and s icam1 and increased expression of cd146 , CD31 , and ICAM 1 in endothelial cells …

T cell mediated immune mechanisms in myositis. (1996 Mar)
T cell mediated immune mechanisms in myositis . advances in molecular biologic techniques and the availability of novel immunologic reagents have allowed new approaches to understanding the pathogenesis of human autoimmune diseases , including the idiopathic inflammatory myopathies . indirect evidence that autoreactive T cells mediate muscle inflammation in the human myositis syndromes has been strengthened by recent studies describing restricted T cell receptor gene expression in certain clinical and / or serologic groups of myositis patients . these findings are supported by other investigations documenting abnormal patterns of cytokine , adhesion molecule , and major histocompatibility complex antigen expression within inflammatory lesions . The major challenge of future studies is to identify the specific antigen ( s ) responsible for initiating and perpetuating these harmful immune responses .