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 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.     

Pathogenesis and therapies of immune-mediated myopathies

The most common autoimmune muscle disorders include dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion body myositis (sIBM). DM is a complement-mediated microangiopathy leading to destruction of capillaries, hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmunity with macrophages as the final effector cells causing fiber injury. PM and IBM are T cell-mediated disorders where cytotoxic CD8(+) T cells clonally expand in situ and invade major histocompatibility complex class I expressing muscle fibers. In sIBM, in addition to autoreactive T cells, there are degenerative features characterized by vacuolization and accumulation of stressor or amyloid-related misfolded proteins; an interrelationship between inflammatory and degeneration-associated molecules is prominent and enhances the cascade of pathogenic factors. These disorders are treatable, hence the need to make the correct diagnosis from the outset. The applied therapeutic strategies are outlined and the promising new agents are reviewed.     

Mononuclear cells in myopathies: quantitation of functionally distinct subsets, recognition of antigen-specific cell-mediated cytotoxicity in some diseases, and implications for the pathogenesis of the different inflammatory myopathies

Monoclonal antibodies reactive for B cells, T cells, T-cell subsets, killer (K) and natural killer (NK) cells, and the Ia antigen were used to analyze mononuclear cell subsets in scleroderma (SD), dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), Duchenne dystrophy (DD), and normal muscle. The analysis, which was quantitative, was performed according to diagnosis and site of accumulation. Cells at perivascular, perimysial, and endomysial sites of accumulation, and cells focally surrounding and invading nonnecrotic muscle fibers, were analyzed separately. Individual antigens were localized in 2-micron serial sections, or multiple antigens were demonstrated in a given section by sequential paired immunofluorescence. The latter approach allowed the identification of the cell phenotypes in which functional properties are defined by multiple markers, e.g., T8+ and T4+ cells that are either activated or not activated, T8+ cells that are either cytotoxic or suppressor T cells, and K/NK cells of varying maturity and killing capability. The interactions of inflammatory cells of various types with each other and the muscle fiber were further investigated by immunoelectron microscopy. In SD, the findings provide evidence for a cell-mediated immune effector response against a connective tissue and/or vascular element. In DM, the effector response appears to be predominantly humoral. In PM and IBM (but not in DM or SD), there is invasion and destruction of nonnecrotic muscle fibers by cytotoxic T cells, with or without accompanying macrophages. Because T-cell-mediated injury is antigen- and major histocompatibility complex-restricted, clones of T cells must have been sensitized previously to a muscle fiber-associated surface antigen. The identity of the putative antigen(s) remains an important, unsolved question.     

Ubiquitin immunostaining and inclusion body myositis: Study of 30 patients with inclusion body myositis

Distinction of inclusion body myositis (IBM) from other forms of inflammatory myopathy is significant from prognostic and therapeutic standpoints. This study retrospectively examines ubiquitin expression by paraffin immunohistochemistry in muscle biopsy material from 30 patients with IBM. Patients included 19 men and 11 women (ages 29 to 80 years; mean, 64 years). All biopsies were characterized by endomysial chronic inflammation, muscle fiber degeneration and regeneration, rimmed vacuoles, and angular atrophic esterase-positive muscle fibers. Ragged red fibers were identified in biopsies of five patients and a partial cytochrome C-oxidase deficiency by enzyme histochemistry in biopsies of 10 patients. Evidence of intranuclear or cytoplasmic tubulofilamentous structures confirming a diagnosis of IBM was observed in all 30 cases. Paracrystalline mitochondrial inclusions were noted in five patients. Discrete myocyte intranuclear ubiquitin-positive inclusions were noted in 14 patients (47%). Discrete intracytoplasmic ubiquitin-positive inclusions were noted in 24 (80%) patients. Positive staining of rimmed vacuoles by ubiquitin was observed in 25 (83%) patients. Diffuse staining of scattered muscle fibers was observed in 21 (70%) patients. In a control group including patients with polymyositis (n = 3), dermatomyositis (n = 3), necrotizing vasculitis (n = 1), and granulomatous myositis (n = 1), discrete intranuclear or cytoplasmic ubiquitin-positive inclusions were not observed. Rimmed vacuoles were not seen either by light microscopy or ubiquitin immunostaining in any of the eight cases. Occasional myofibers from all eight cases showed diffuse, positive muscle fiber staining. Although not present in all cases, evidence of ubiquitinpositive myocytic intranuclear or cytoplasmic inclusions or positive-staining rimmed vacuoles in the setting of an inflammatory myopathy may be suggestive of a diagnosis of inclusion body myositis. Use of ubiquitin immunohistochemistry may be useful in cases in which frozen tissue or tissue processed for electron microscopy is not available, and IBM is suspected. Light or electron microscopic evidence of mitochondrial abnormalities were noted in a significant subset of patients (13 of 30; 43%) of patients with IBM.     

Update on idiopathic inflammatory myopathies

The inflammatory myopathies are a group of acquired diseases, characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical, immuno-pathological and demographic features, three major diseases can be identified: dermatomyositis (DM); polymyositis (PM); and inclusion body myositis (IBM). New diagnostic criteria have recently been introduced, which are crucial for discriminating between the three different subsets of inflammatory myopathies and for excluding other disorders. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens, thus leading to fibre necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the main clinical, laboratory, electrophysiological, immunological and histologic features as well as the therapeutic options of the inflammatory myopathies.     

Immune checkpoint failures in inflammatory myopathies: An overview

Dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), immune mediated necrotizing myopathy (IMNM) and overlap myositis (OM) are classified as inflammatory myopathies (IM) with involvement of autoimmune features such as autoreactive lymphocytes and autoantibodies. Autoimmunity can be defined as a loss in self-tolerance and attack of autoantigens by the immune system. Self-tolerance is achieved by a group of immune mechanisms occurring in central and periphal lymphoid organs and tissues, called immune checkpoints, that work in synergy to protect the body from harmful immune reactions. Autoimmune disorders appear when immune checkpoints fail. In this review, the different immune checkpoint failures are discussed in DM, PM, IBM and IMNM. Exploring research contribution in each of these immune checkpoints might help to highlight research perspectives in the field and obtain a more complete picture of IM disease pathology.     

Restricted use of T cell receptor V genes in endomysial infiltrates of patients with inflammatory myopathies

Inclusion body myositis (IBM), polymyositis (PM) and dermatomyositis (DM) are diseases characterized clinically by progressive muscle weakness and histologically by T lymphocyte infiltrates in striated muscle. The pathogenetic role of these cells is proposed to be cell-mediated cytotoxicity in PM and IBM, but the exact mechanisms of their action are poorly understood. Characterization of the variable regions of T cell receptors (TcR) on the infiltrating lymphocytes may be expected to provide insights into the mechanisms of local activation of the immune system in inflammatory myopathies. Immunohistochemical analysis using a panel of monoclonal antibodies specific for 11 Vα/β TcR was performed on cryosectioned muscle biopsy specimens from eight patients with IBM, eight with PM and three with DM. In addition, TcR expression was studied in inflammatory infiltrates in skin biopsies obtained from some of the IBM patients challenged locally with tuberculin. Flow cytometry was used to assess expression of TcR on peripheral blood lymphocytes. All the patients displayed a clear restriction of TcR usage, preferentially limited to Vα2 and Vβ3 TcR families in the endomysial, but not in perivascular infiltrates, even within the same muscle specimen. Such a restriction was not found in skin punch biopsies or PBL from the same subjects. Our results suggest that T cells extravasate non-selectively to the skeletal muscle, but once there, only certain TcR families proliferate, presumably after encounter with a locally exposed superantigen.     

Differential Immunohistological Features of Inflammatory Myopathies and Dysferlinopathy

This study was performed in order to characterize the types of the infiltrating cells, and the expression profiles of major histocompatibility complex (MHC) class I and membrane attack complex (MAC) in patients with inflammatory myopathies and dysferlinopathy. Immunohistochemical stains were performed using monoclonal antibodies against several inflammatory cell types, MHC class I, and MAC in muscles from inflammatory myopathies and dysferlinopathy. There was significant difference in the types of infiltrating cells between polymyositis (PM), dermatomyositis (DM), and dysferlinopathy, including significantly high CD4+/CD8+ T cell ratio and B/T cell ratio in DM. In dysferlinopathy, CD4+ T cells were the most abundant and the proportions of infiltrating cell types were similar to those of DM. MHC class I was expressed in muscle fibers of PM and DM regardless of the presence of inflammatory infiltrates. MAC was expressed in necrotic fibers and vessels of PM and DM. One patient with early stage DM had a MAC deposits on endomysial capillaries. In dysferlinopathy, MAC deposit was also observed on the sarcolemma of nonnecrotic fibers. The analysis of inflammatory cells, MHC class I expressions and MAC deposits may help to differentiate dysferlinopathy from idiopathic inflammatory myopathy.     

Polymyositis with cytochrome C oxidase negative fibers—a pathological and clinical challenge

Polymyositis (PM) with cytochrome C oxidase negative fibers also referred to as PM with mitochondrial pathology (PM-Mito) is characterized by the symptoms of inclusion body myositis (IBM) and by the myopathological findings of PM except for an increase of muscle fibers with insufficient mitochondrial cytochrome C oxidase activity. Few PM-Mito cases are published; mitochondrial ultrastructure has not been studied in these patients. We report 2 PM-Mito patients with later onset than usually seen in IBM and poor responsiveness to glucocorticoids. Electron microscopy of muscle fibers showed irregular mitochondrial ultrastructure. Sjögren syndrome related antinuclear antibodies (Anti-Ro and Anti-La) were found in one of the two patients but the typical clinical symptoms of Sjögren syndrome such as xerostomia and keratoconjunctivitis were absent in this patient. Taken together, our observations, viewed in conjunction with the current literature, suggest that PM-Mito is an underdiagnosed disease with a multifactorial pathogenesis that should be elucidated in further studies. We want to encourage clinicians and pathologists to consider the possibility of PM-Mito in patients with atypical PM or sIBM.     

The type I interferon system in idiopathic inflammatory myopathies

Polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) are chronic inflammatory diseases that are characterized by muscle weakness and inflammatory cells in muscle tissue. Autoantibodies are common, some of them are specific for myositis, the most frequent being the anti-Jo-1 antibody which is associated not only with myositis but also with interstitial lung disease and arthritis. A role of type I interferons in disease mechanisms of myositis was first supported by the reported onset of PM and DM during treatment with type I interferon. More recently an interferon signature has been reported in muscle tissue of DM and PM patients both as gene and protein expression, and type I IFN expression in peripheral blood cells seems to correlate with disease activity. Different mechanisms could induce type I interferon in PM and DM like viral infections or endogenous factors as suggested by the observation that sera from myositis patients with anti-Jo-1 antibodies as well as anti-SSA and anti-SSB antibodies have an interferon inducible capacity. Accumulating data indicate a role of the type I interferon in myositis, particularly in juvenile and adult DM and in anti-Jo-1 or anti-SSA positive PM.     

Analysis of multiple mitochondrial DNA deletions in inclusion body myositis

Inclusion body myositis (IBM) is a sporadic progressive myopathy, which is morphologically characterized by inflammatory cell infiltrates and rimmed vacuoles in muscle fibers. Mitochondrial changes are regularly present with ragged-red fibers showing deficiency of cytochrome c oxidase. In these muscle fiber segments, there is accumulation of mitochondria with mitochondrial DNA (mtDNA) deletions. There are different deletions in different muscle fibers. In this study, we have sequenced for the first time the multiple mtDNA deletions in muscle from four patients with IBM. The deletion breakpoints were sequenced from cloned polymerase chain reaction (PCR)-amplified mtDNA fragments. The sequencing was performed directly from the bacterial colonies used for cloning. Of 122 analyzed clones, 33 different deletions were identified. The majority of these have not previously been described. There was a marked predominance of deletion breakpoints in certain regions of mtDNA. These predominant breakpoint regions are similar to those described in other conditions with multiple deletions, such as autosomal dominant progressive external ophthalmoplegia (adPEO) and normal aging, but different from those described in diseases due to single deletions such as Kearns-Sayre syndrome and sporadic PEO. These findings indicate that common factors are involved in the development of multiple mtDNA deletions in IBM, adPEO, and aging. Hum Mutat 10:381–386, 1997. © 1997 Wiley-Liss, Inc.     

Light and electron microscopic immunolocalization of presenilin 1 in abnormal muscle fibers of patients with sporadic inclusion-body myositis and autosomal-recessive inclusion-body myopathy.

Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older persons. The muscle biopsy demonstrates mononuclear cell inflammation and vacuolated muscle fibers containing paired helical filaments and 6- to 10-nm fibrils, both resembling those of Alzheimer disease brain and Congo red positivity. The term hereditary inclusion-body myopathies (h-IBMs) designates autosomal-recessive or autosomal-dominant disorders with muscle biopsies cytopathologically similar to s-IBM but without inflammation. Vacuolated muscle fibers of both s-IBM and the h-IBMs contain accumulations of several "Alzheimer-characteristic proteins" including beta-amyloid protein and beta-amyloid precursor protein, and their paired helical filaments are composed of phosphorylated tau. We used six well characterized antibodies against several residues of presenilin 1 (PS1) to immunostain muscle biopsies of 12 patients with s-IBM, 5 patients with autosomal-recessive inclusion-body myopathy, and 16 normal and disease controls. Seventy to eighty percent of the vacuolated muscle fibers of both s-IBM and autosomal-recessive inclusion-body myopathy had inclusions that were strongly PS1-immunoreactive, which by immunoelectron microscopy localized mainly to paired helical filaments and 6- to 10-nm filaments. None of the control biopsies had PS1-positive inclusions characteristic of the s- and h-IBM abnormal muscle fibers. Mutations of the newly discovered PS1 gene are responsible for early-onset familial Alzheimer disease (AD), and PS1 is abnormally accumulated in sporadic and familial AD brain. Our study provides the first demonstration of PS1 abnormality in non-neural tissue and in diseases other than AD and suggests that the cytopathogenesis in AD brain and IBM muscle may share similarities.     

Inclusion body myositis: from immunopathology and degenerative mechanisms to treatment perspectives

Inclusion body myositis is the most common inflammatory myopathy above the age of 50. It becomes clinically apparent around the fourth decade and leads to a slowly, but relentlessly progressive decline in muscular wasting and weakness. The pathology consists of a complex network of inflammatory and degenerative mechanisms, which lead to an attack of muscle fibers by auto-reactive T cells and possibly antibodies. At the same time, various aberrant proteins accumulate within the muscle fibers, including β-amyloid, tau and α-synuclein. Several key components of proinflammatory cell stress mechanisms such as nitric oxide production and macroautophagic processing contribute to the muscle fiber damage. So far, none of the anti-inflammatory or immunomodulatory treatment efforts have been able to halt the disease progression and help the patients. In this summary, the current concept of the complex disease pathology of IBM is reviewed with a focus on recent findings as well as future treatment perspectives.     

Inclusion body myositis: a chronic persistent mumps myositis?

Among the generalized chronic idiopathic inflammatory myopathies, inclusion body myositis (IBM) has emerged as a clinico-pathologic variant during the past two decades. It occurs primarily in elderly persons (in approximately the sixth decade of life), but young adults (in approximately the second decade of life) may also be affected. Slowly progressive weakness of distal as well as proximal muscle groups in IBM is usually not associated with skin rash, malignancy or collagen-vascular disease, and is refractory to treatment with steroids or other immunosuppressants. Exceptions to each of these general rules have been found. Muscle biopsy and electromyography may suggest a neurogenic process mixed with myopathic features. Rimmed vacuoles with basophilic granules in cryostat sections stained with hematoxylin-eosin are strongly suggestive of IBM if accompanied by the histopathologic triad of polymyositis. The presence of eosinophilic intranuclear or cytoplasmic inclusions in affected myofibers is further suggestive of IBM. The ultimate diagnosis, however, depends on ultrastructural demonstration of characteristic microtubular filaments resembling the nucleocapsids of the paramyxovirus group. Recent reports of immunostaining of the inclusions for mumps virus antigen strongly suggest a chronic persistent mumps virus infection as the cause of IBM. IBM is considered to be pathologically related to both distal myopathy (DM) and oculopharyngeal muscular dystrophy (OPMD).     

Pathogenic accumulation of APP in fast twitch muscle of IBM patients and a transgenic model

Inclusion body myositis (IBM) is the most common age-related degenerative skeletal muscle disorder. The aberrant intracellular accumulation of the beta-amyloid (Abeta) peptide within skeletal muscle is a pathological hallmark of IBM. Skeletal muscle is comprised of both slow and fast twitch fibers, which are present in different proportions in various muscles. It remains unclear if fast and/or slow twitch fibers are differentially involved in IBM pathogenesis. To better understand the molecular pathogenesis of IBM, we analyzed human IBM muscle biopsies and muscle from a transgenic mouse model of IBM (MCK-betaAPP). Here we report that the majority of histopathologically-affected fibers in human IBM biopsies were type II fast fibers. Skeletal muscle from MCK-betaAPP mice exhibited higher transgene expression and steady-state levels of human betaAPP in fast type IIB fibers compared to slow type I fibers. These findings indicate that fast twitch fibers may selectively accumulate and be more vulnerable to betaAPP- and Abeta-mediated damage in IBM. These findings also highlight parallels between the MCK-betaAPP mice and the human IBM condition.     

Characterization and investigation of zebrafish models of filamin-related myofibrillar myopathy

Myofibrillar myopathies are a group of muscle disorders characterized by the disintegration of skeletal muscle fibers and formation of sarcomeric protein aggregates. All the proteins known to be involved in myofibrillar myopathies localize to a region of the sarcomere known as the Z-disk, the site at which defects are first observed. Given the common cellular phenotype observed in this group of disorders, it is thought that there is a common mechanism of pathology. Mutations in filamin C, which has several proposed roles in the development and function of skeletal muscle, can result in filamin-related myofibrillar myopathy. The lack of a suitable animal model system has limited investigation into the mechanism of pathology in this disease and the role of filamin C in muscle development. Here, we characterize stretched out (sot), a zebrafish filamin Cb mutant, together with targeted knockdown of zebrafish filamin Ca, revealing fiber dissolution and formation of protein aggregates strikingly similar to those seen in filamin-related myofibrillar myopathies. Through knockdown of both zebrafish filamin C homologues, we demonstrate that filamin C is not required for fiber specification and that fiber damage is a consequence of muscle activity. The remarkable similarities in the myopathology between our models and filamin-related myofibrillar myopathy makes them suitable for the study of these diseases and provides unique opportunities for the investigation of the function of filamin C in muscle and development of therapies.     

Diagnosis,pathogenesis and treatment of myositis: recent advances

Dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM) and inclusion body myositis (IBM) are four distinct subtypes of idiopathic inflammatory myopathies – in short myositis. Recent studies have shed some light on the unique pathogenesis of each entity. Some of the clinical features are distinct, but muscle biopsy is indispensable for making a reliable diagnosis. The use of magnetic resonance imaging of skeletal muscles and detection of myositis‐specific autoantibodies have become useful additions to our diagnostic repertoire. Only few controlled trials are available to substantiate current treatment approaches for myositis and hopes are high that novel modalities will become available within the next few years. In this review we provide an up‐to‐date overview of the pathogenesis and diagnostic approach of myositis. We aim to present a guide towards therapeutic and general management.     

Skeletal muscle development in normal and double-muscled cattle

This study examined the effect of genotype on prenatal muscle development in both normal-muscled (NM) animals and in double-muscled (DM) animals harboring a mutation in the gene for myostatin that results in the production of a functionally inactive protein. The following muscle development parameters were analyzed at four gestational ages: muscle weight, fiber type, by both enzyme histochemistry and myosin heavy-chain (MHC) immunocytochemistry, and average fiber area. The weights of both M. vastus lateralis and M. vastus medialis were greater throughout prenatal development in the DM animals compared to NM. The percentage of type 1 muscle fibers initially declined with gestational age and subsequently increased in both NM and DM. The percentage of type 1 fibers was consistently lower in DM than in NM. A pattern of MHC isoform localization was shown in DM muscle that is indicative of a delay in muscle development relative to NM. Muscle fiber size was differentially regulated in NM and DM, depending on fiber type. Type 1 fibers were smaller in DM than NM in late gestation, while type 2 fibers were smaller throughout gestation. This study suggests that the inactivating myostatin mutation in DM animals may be associated with changes in both skeletal muscle fiber type and fiber size during bovine muscle development.     

Altered RIG‐I/DDX58‐mediated innate immunity in dermatomyositis

We investigated the molecular mechanisms involved in the pathogenesis of three inflammatory myopathies, dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). We performed microarray experiments^? using microdissected pathological muscle fibres from 15 patients with these disorders and five controls. Differentially expressed candidate genes were validated by immunohistochemistry on muscle biopsies, and the altered pathways were analysed in human myotube cultures. Up‐regulation of genes involved in viral and nucleic acid recognition were found in the three myopathies but not in controls. In DM, retinoic acid‐inducible gene 1 (RIG‐I, DDX58) and the novel antiviral factor DDX60, which promotes RIG‐I‐mediated signalling, were significantly up‐regulated, followed by IFIH1 (MDA5) and TLR3. Immunohistochemistry confirmed over‐expression of RIG‐I in pathological muscle fibres in 5/5 DM, 0/5 PM and 0/5 IBM patients, and in 0/5 controls. Stimulation of human myotubes with a ligand of RIG‐I produced a significant secretion of interferon‐β (IFNβ; p < 0.05) and up‐regulation of class I MHC, RIG‐I and TLR3 (p < 0.05) by IFNβ‐dependent and TLR3‐independent mechanisms. RIG‐I‐mediated innate immunity, triggered by a viral or damage signal, plays a significant role in the pathogenesis of DM, but not in that of PM or IBM. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd     

Can tissue transglutaminase be a marker of idiopathic inflammatory myopathies?

In the normal striated muscle, tissue transglutaminase (TG2) content is vestigial. However, this protein's presence has been reported to occur in myoblasts and myotubes during the fetal period. Its increased expression has been also found in the muscle tissue in the course of sporadic inclusion body myositis, as well as in polymyositis (PM) and dermatomyositis (DM), which are considered to be diseases of immunological origin. Based on in vitro studies, a substantial TG2 role in the infiltration of some T cell subsets into inflamed tissues has been suggested lately. In this study, the immunohistochemical reactions in the guinea pig experimental myositis specimens and in the ones from PM/DM patients were compared. The guinea pig tissue specimens were taken from muscles affected by experimental myositis induced by intramuscular injections of: 1/sera from 30 neoplasm patients with no metastases; 2/sera from 10 healthy people; 3/sera from 2 DM patients; 4/neuropeptides (SP, NPY or VIP) and from 5/the muscles affected by the reversed passive Arthus reaction (RPAR). The immunostaining for TG2 revealed substantial presence of this protein in single, damaged muscle fibers and a weak reaction in regenerating fibers appearing in PM/DM patients' specimens. From among experimental myositis specimens, a very intensive reaction appeared only in the damaged and regenerating muscle fibers present in the slides from guinea pig muscles injected with DM patients' sera. Such results suggest some presence of a specific factor(s) (the one(s) responsible for TG2 expression in the damaged muscle fibers) in DM patients' sera. The results suggest that transglutaminase can be a marker of inflammatory myopathies. A probable correlation between TG2 expression in muscles and organismal immunological factors, including the complement activation status, requires additional studies.