Materiały źródłowe

• #1 Idiopathic inflammatory myopathies: pathogenic mechanisms of muscle weakness | Skeletal Muscle | Full Text

  https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/2044-5040-3-13

  Idiopathic inflammatory myopathies (IIMs) are a heterogenous group of complex muscle diseases of unknown etiology. It is generally believed that the autoimmune response (autoreactive lymphocytes and autoantibodies) to skeletal muscle-derived antigens is responsible for the muscle fiber damage and muscle weakness in this group of disorders. […] Recent studies have indicated that the underlying mechanisms that mediate muscle damage and dysfunction are multiple and complex. Emerging evidence indicates that not only autoimmune responses but also innate immune and non-immune metabolic pathways contribute to disease pathogenesis. […] The relative contribution of the autoimmune component to myositis pathogenesis is not yet known. Recent data suggest that innate immune activation and metabolic defects occur in the myositis muscle, suggesting a role for these pathways in disease pathogenesis.

• #2 Pathophysiological Mechanisms and Treatment of Dermatomyositis and Immune Mediated Necrotizing Myopathies: A Focused Review

  https://www.mdpi.com/1422-0067/23/8/4301

  Idiopathic inflammatory myopathies (IIM), collectively known as myositis, are a composite group of rare autoimmune diseases affecting mostly skeletal muscle, although other organs or tissues may also be involved. […] Various components of the immune system are known to be important immunopathogenic pathways in IIM, although the exact pathophysiological mechanisms causing the muscle damage remain unknown. […] A better understanding of the overlapping and diverging pathophysiological mechanisms of the major subgroups of myositis is needed to optimize treatment. […] In recent decades, both adaptive and innate immune mechanisms have been shown to contribute to the pathogenesis of IIM. […] Immune-mediated disease mechanisms are thought to encompass both adaptive and innate disease mechanisms.

• #3 Diagnosis, pathogenesis and treatment of myositis: recent advances

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3927896/

  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. […] The pathology of DM includes binding of immune complexes to endothelium cells with subsequent activation of the complement system and cell lysis, mediated by the membrane-attack complex (MAC). This leads to necrosis of these cells, and a reduced number of capillaries in the muscle can be seen. The blood supply becomes insufficient, which is believed to cause perifascicular atrophy. […] This classical concept has been challenged recently, in that Greenberg’s group reported a type I interferon (IFN)-mediated cascade and suggest that this is a predominant element of the pathology. The type I IFN-(/)-induced genes are overexpressed in muscle, skin and blood and correlate significantly with the disease activity.

• #4 Risk Factors and Disease Mechanisms in Myositis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6745704/

  Autoimmune diseases develop as a result of chronic inflammation owing to interactions between genes and the environment. However, the mechanisms by which autoimmune diseases evolve remain poorly understood. Newly discovered risk factors and pathogenic processes in idiopathic inflammatory myopathy (IIM) phenotypes have illuminated innovative approaches for understanding these diseases. The HLA 8.1 ancestral haplotype is a key risk factor for major IIM phenotypes in white populations, and genetic risk variants for other autoimmune diseases have been identified as IIM risk factors. Environmental risk factors are less studied but might include viruses, bacteria, ultraviolet radiation, smoking, occupational and perinatal exposures and a growing list of drugs, biologics, and dietary supplements. Disease mechanisms vary by phenotype, with evidence for shared innate and adaptive immune and metabolic pathways in some phenotypes but unique pathways in others. The heterogeneity and rarity of the IIMs make advancements in diagnosis and treatment cumbersome.

• #5 Risk Factors and Disease Mechanisms in Myositis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6745704/

  The pathomechanisms of most immune-mediated diseases relate to chronic organ inflammation that can be caused by specific interactions between genetic and environmental risk factors. Immune activation in such diseases often involves both innate and adaptive mechanisms, as well as other non-immune mechanisms; however, the details and the interactions of different pathways are usually not clear. […] By identifying the genes associated with IIM, studies can focus on the molecular pathways involved and thereby improve our understanding of IIM pathogenesis. The strong association between IIM subsets and HLA-DR and HLA-DQ genes supports a role for the adaptive immune system in the pathogenesis of IIM, as a key role of HLA class molecules is to present antigens to T cells. […] Despite the small contribution of identified genetic variants to clinical phenotypes, drugs targeting the pathways affected by genetic variations might be disproportionately effective. In IIM, the application of drugs repurposed from other diseases will probably become more important as our understanding of disease mechanisms evolve.

• #6 Risk Factors and Disease Mechanisms in Myositis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6745704/

  The presence of significant inflammation in the muscle of juvenile dermatomyositis patients despite a high proportion of Treg cells in the milieu suggests that Treg cell function is impaired. […] The presence of autoantibodies, including autoantibodies to Mi-2, SUMO-activating enzyme, melanoma differentiation-associated gene 5, signal recognition particle, transcription intermediary factor 1, and anti-PL-7, have been associated with specific HLA alleles. […] The finding that different HLA alleles have been associated with various myositis-specific autoantibody-defined subgroups agrees with the finding that many MSAs are mutually exclusive. […] In IBM, specific genes implicate both inflammatory and degenerative changes, including mitochondrial abnormalities, in disease pathogenesis. […] The suggestion that non-immune-mediated mechanisms are clinically relevant in IIM derives from a number of key findings: the muscular inflammation identified by muscle biopsy and MRI does not always correlate with the clinical severity; the effects of immunosuppressive treatments can be limited; and several non-inflammatory mechanisms, including cell stress and degenerative mechanisms, are obvious in many muscle biopsies.

• #7 Risk Factors and Disease Mechanisms in Myositis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6745704/

  The pathogenesis of IIM cannot be explained solely by genetic risk factors. Many of the variants identified have a relatively small effect on disease risk individually, and only 5.5%16% of the phenotypic variance can be explained by genetic variants identified from Immunochip studies. […] Although a number of genes have been associated with the IIMs, the physiologic effect of these genes might depend on their activation or modification by environmental factors. […] Multiple lines of evidence suggest that autoimmune diseases have an environmental component: the concordance rates for autoimmune diseases in monozygotic twins is much less than 50%; there are strong temporal associations between certain exposures (infectious agents and drugs in particular) and the subsequent development of some autoimmune diseases; in some individuals, disease improves after removing a suspected environmental agent (dechallenge) and/or worsens or reoccurs after re-exposure to the suspected agent (rechallenge); the incidence of many autoimmune diseases has increased over time; there are seasonal and geographic variations in disease onset and in birth dates of individuals who have developed an autoimmune disease; data from relevant animal models have demonstrated the plausibility of multiple environmental agents potentially triggering autoimmune disease; the major genetic risk factors for autoimmunity are polymorphic genes that regulate responses to environmental agents; variations in the human immune system are largely driven by nonheritable influences; and associations between specific exposures and autoimmune diseases have been documented in large epidemiologic studies.

• #8 Infectious Myositis: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1168167-overview

  Infectious myositis is an acute, subacute, or chronic infection of skeletal muscle. […] Viruses implicated in the pathogenesis of myositis include HIV-1, human T lymphotrophic virus 1 (HTLV-1), influenza, coxsackieviruses, and echoviruses. […] Lyme myositis may result from direct invasion of muscle by the spirochete Borrelia burgdorferi or by autoimmune mechanisms. […] The pathogenesis is unclear, but trauma, viral infection, and malnutrition have been implicated. […] In humans, the parasite loses its flagellum and transforms into the amastigote form, which may enter muscle and multiply, resulting in myositis.

• #9 Diagnosis, pathogenesis and treatment of myositis: recent advances

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3927896/

  The pathogenesis is characterized by local activation of immune cells in skeletal muscle. The proinflammatory milieu includes expression of cytokines such as IFN-, IL-6, IL-1, tumour necrosis factor (TNF)- and TGF-, as well as chemokines such as IL-8, CCL-2, CCL-3, CCL-4, CCL-5, CXCL-9 and CXCL-10, contributing to the local inflammation, and are the attracting stimulus for immune cells. […] The interaction of these cells is hypothesized to play an important role in the progression and pathogenesis of NM, but the major part of the pathogenesis is still unknown. […] The inflammatory process is similar to PM, with an invasion of non-necrotic fibres by macrophages and cytotoxic CD8+ T cells. There is an over-expression of metalloproteinaeses 2 and 9 on non-necrotic muscle fibres, as in PM.

• #10 Risk Factors and Disease Mechanisms in Myositis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6745704/

  The compelling data that reveal a link between the environment and autoimmunity, as well as the remarkable increases in the incidence and prevalence of many autoimmune diseases for unknown reasons, underscore a critical need for both exploratory and confirmatory environmental investigations in this understudied field. Identifying factors that protect against disease is also important to decrease the prevalence of autoimmune disease. […] Preliminary data suggest that many adaptive and innate immune mechanisms, as well as non-immune mechanisms, are involved in the development of the IIMs. […] The invasion of CD8+ effector cells into non-necrotic muscle fibres is considered a characteristic histological feature of polymyositis and IBM. […] The presence of MSAs, such as anti-Jo1, anti-Mi2, anti-cytosolic 5-nucleotidase 1A (cN1A), or anti-HMGCR autoantibodies, are well described in patients with polymyositis, dermatomyositis, IBM, or necrotizing myopathy, respectively.

• #11

  https://link.springer.com/article/10.1007/s11926-024-01164-7

  Recent research has revealed that myositis-specific autoantibodies can infiltrate muscle cells and disrupt the function of their target autoantigens, playing a crucial role in disease pathogenesis. […] Autoimmune myopathies are a collection of disorders significantly influenced by specific autoantibodies that drive disease pathogenesis. […] Our understanding of the pathogenesis of myositis has evolved significantly over the years due to epidemiologic advances and molecular research. […] A critical advancement has been the discovery of multiple autoantibodies that define groups of myositis patients with unique clinical features, prognosis, and response to treatment. […] Recent efforts have focused on identifying the pathogenesis of different myositis autoantibodies by analyzing their specific clinical, histopathological, and molecular differences.

• #12 Pathological autoantibody internalisation in myositis | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/83/11/1549

  Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption. […] In patients with myositis autoantibodies, antibodies accumulate inside myofibres in the same subcellular compartment as the autoantigen. […] Muscle biopsies from patients with autoantibodies targeting transcriptional regulators exhibit transcriptomic patterns consistent with dysfunction of the autoantigen. […] Introducing patient antibodies into cultured muscle cells recapitulated the transcriptomic effects observed in human disease. […] This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen.

• #13 Pathological autoantibody internalisation in myositis | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/83/11/1549

  We recently showed that in muscle tissue from patients with anti-Mi2 autoantibodies, antibodies are deposited in the nuclei of muscle fibres, which is also where the Mi2 autoantigen is located. […] These findings suggested that anti-Mi2 autoantibodies reach the Mi2/NuRD complex within muscle cell nuclei and disrupt its function, leading to aberrant expression of genes normally repressed by that complex. […] Taken together, these studies show that myositis autoantibodies reach their intracellular targets. […] Furthermore, we provide strong evidence that autoantibodies against Mi2 and exosome components 9 and 10 (anti-PM/Scl autoantibodies) disrupt the normal function of these proteins. […] This study reveals two novel features in myositis. First, our immunofluorescence analyses demonstrate that antibodies are internalised within living human muscle cells from patients with a variety of myositis autoantibodies and that they localise to the site of the corresponding target autoantigen. Second, using antibody internalisation experiments along with transcriptomic analyses, we have shown that these internalised autoantibodies disrupt the normal function of their protein targets. […] These findings disprove the conventional assumption that myositis autoantibodies are incapable of reaching their intracellular target and exerting a functional effect.

• #14

  https://journals.lww.com/ijru/fulltext/2020/15002/pathogenesis_of_muscle_weakness_in_inflammatory.5.aspx

  The pathways that trigger immune response in IIM are common to various pathophysiological processes, inducing muscle weakness. These immune pathways once triggered can result in damage to muscle fibers, impair regeneration of the damaged muscle fibers, decrease contractility, and upregulate nonimmune pathways. […] In early disease, Type 1 IFN and the IFN-responsive elements seem to mediate microvascular changes. IFN is primal to vessel health, and dysregulated IFN production is associated with endothelial damage and clumping which is suggested by the presence of noninflammatory occlusive vasculopathy and capillary loss in IIM. The complement pathway also appears to play a major role in the endothelium damage, and C5b9-complement component is detected on the damaged endothelium in the necrotic endothelium. This further strengthens the links between microvascular dysfunction and loss of muscle fibers, eventually resulting in muscle weakness.

• #15 Idiopathic inflammatory myopathies: pathogenic mechanisms of muscle weakness | Skeletal Muscle | Full Text

  https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/2044-5040-3-13

  Thus, the emerging paradigm indicates that not only innate and adaptive immune mechanisms but also intrinsic defects in skeletal muscle contribute to muscle weakness and damage in myositis. […] The muscle microenvironment is complex, and we propose that active interactions occur between innate, adaptive, metabolic and homeostatic pathways in muscle in these diseases. […] It is likely that some DAMPs leak from the injured skeletal muscle and engage their receptors on both skeletal muscle and immune cells, thereby perpetuating the inflammatory process. […] These findings suggest that TLR receptors are engaged in the milieu of affected muscle and that the downstream genes are activated. […] Taken together, these studies clearly suggest that TLRs, acting through MyD88-dependent and/or independent mechanisms, induce pro-inflammatory signals in myopathic muscle.

• #16 A Review of Myositis-Associated Interstitial Lung Disease

  https://www.mdpi.com/2077-0383/13/14/4055

  The cytotoxic T cells possess perforin containing cytoplasmic granules, which when released induce necrosis of the muscle cells. […] Immunoglobulin and complement proteins are found in the vessels of muscle tissue from these patients, which may help to promote muscle damage. […] Plasmacytoid dendritic cells (pDC) are also present in the muscle and skin of patients with DM and produce type I interferons, which promote inflammation and T and B cell activation. […] The exact role of the MSAs found in patients with PM and DM is not clear. […] Toll-like receptors (TLRs) are expressed on myocytes in patients with PM and DM. […] This suggests that activation of myocytes through TLRs recruits immune cells, leading to the production of pro-inflammatory cytokines. […] Other studied mechanisms of pathogenesis include the adaptive immune system; B cells activated to plasmablasts and plasma cells to produce autoantibodies and T cells to produce IL-6, IL-17, IFN-γ, and BAFF; and the innate immune system, including macrophages and pDC, producing IL-1, IL-6, IL-15., IL-23, and IFN-α and γ.

• #17 Idiopathic inflammatory myopathies: pathogenic mechanisms of muscle weakness | Skeletal Muscle | Full Text

  https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/2044-5040-3-13

  The NF-kB pathway is one of the predominant regulators of a variety of essential biological processes, including inflammation. […] In myositis both immune and skeletal muscle cells modulate inflammation via the NF-kB pathway. […] The inflammasome pathway is connected to the TLR signaling pathway. […] In myositis, the activation of inflammasomes and the subsequent release of cytokines in affected muscle have not yet been investigated; however, enhanced expression of both TLRs and IL-1 and IL-1 in areas surrounded by inflammatory cells suggest that TLR-inflammasome pathway is active in myositis muscle. […] The emerging picture indicates that myositis is a complex disease with multiple pathogenic pathways simultaneously contributing to muscle damage and weakness. Among these, the most prominent are the innate, adaptive immune and metabolic pathways.

• #18 Risk Factors and Disease Mechanisms in Myositis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6745704/

  ER stress is one of the best-studied elements of non-immune-mediated damage to skeletal muscle in all forms of IIM. […] Dysregulation of HMGB1 might also be relevant for the regenerative potential of skeletal muscle in IIM, because HMGB1 is an important factor during recovery and is required for the patient to regain muscle function after severe damage.

• #19 Pathogenesis of Myositis | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-030-15820-0_28

  In this overview of pathogenic mechanisms contributing to the development of idiopathic inflammatory myopathy, we highlight the relative contributions of genetic risk, environmental triggering, adaptive immunity, innate immunity, and nonimmune signaling pathways that culminate in muscular as well as extra-muscular tissue pathology. […] Improved understanding of this complex network will enhance our ability to develop novel therapeutic targets. […] Nonimmune mechanisms of muscle damage in myositis: role of the endoplasmic reticulum stress response and autophagy in the disease pathogenesis. […] Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction. […] The role of TRAIL in mediating autophagy in myositis skeletal muscle: a potential nonimmune mechanism of muscle damage. […] Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies.

• #20 Sporadic Inclusion Body Myositis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1172746-overview

  A specifically proposed mechanism involved in the formation of protein aggregates in s-IBM is inhibition of the ubiquitin-26S proteosome system, which is the primary degradation pathway for misfolded, unfolded, and other damaged proteins. […] Accumulation of unfolded or misfolded proteins in the ER triggers the unfolded protein response (UPR), which is a survival mechanism. […] The UPR comprises (1) the transcriptional induction of ER chaperone proteins to facilitate the folding, processing, and export of secretory proteins; (2) translational attenuation to reduce protein overload; and (3) increased retrotranslocation of misfolded proteins into the cytoplasm for ubiquitination and subsequent proteosomal degradation. […] Several protein kinases are also involved in the s-IBM pathogenic cascade. Kinases that promote tau phosphorylation include cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase-3 (GSK-3).

• #21 Mitochondrial dysfunction and role of harakiri in the pathogenesis of myositis – Institut de Myologie

  https://www.institut-myologie.org/en/2019/08/28/mitochondrial-dysfunction-and-role-of-harakiri-in-the-pathogenesis-of-myositis/

  The etiology of myositis is unknown. […] Here the authors postulate that in individuals with susceptible genetic backgrounds, viral infection alters the epigenome to activate the pathological pathways leading to disease onset. […] Analysis of methylation and gene expression changes identified that a mitochondria-localized activator of apoptosis harakiri (HRK) is upregulated in myositis skeletal muscle cells. […] Increased HRK and TLR7 expression causes mitochondrial damage leading to poor myofiber repair, myofiber death and muscle weakness in myositis patients and exercise induced reduction of HRK and TLR7 expression in patients is associated with disease amelioration.

• #22 Idiopathic Inflammatory Myopathies – Musculoskeletal and Connective Tissue Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/systemic-rheumatic-diseases/idiopathic-inflammatory-myopathies

  Dermatomyositis is characterized by immune complex deposition in the vessels and is considered a complement-mediated vasculopathy. In contrast, polymyositis is characterized by direct T cell-mediated muscle injury, and immune-mediated necrotizing myopathies are characterized by macrophage-predominant infiltrates and myophagocytosis. […] Muscle biopsy is not usually necessary when skin findings are characteristic of dermatomyositis. Although there is no pathognomic skin finding for dermatomyositis on biopsy, the absence of direct immunofluorescence may help distinguish skin findings from the rash in patients with systemic lupus erythematosus. […] Histologic findings in inclusion body myositis include endomysial infiltrates, myofiber degeneration, and rimmed vacuoles, whereas histologic findings in immune-mediated necrotizing myopathy include prominent necrotic muscle fibers with regeneration. There is a paucity of inflammatory infiltrates, but, when present, is composed of macrophage infiltrates.

• #23 Myositis: A Comprehensive Review of Pathogenesis, Diagnosis, And Treatment

  https://www.ijpsjournal.com/article/Myositis+A+Comprehensive+Review+of+Pathogenesis+Diagnosis+And+Treatment

  Myositis refers to a group of rare inflammatory muscle disorders characterized by muscle weakness, fatigue, and chronic inflammation. The exact etiology remains unclear, but genetic predisposition, autoimmune mechanisms, and environmental triggers, including infections and certain medications, are implicated. […] Auto anti-bodies have a strong correlation with illness symptoms. As a result, auto antibodies provide valuable information for clinical diagnosis, classification, prognosis prediction, and therapy decision-making in IIM patients. Over the past decade, new myositis-specific auto antibodies have been discovered. […] DM pathogenesis involves immune complexes attaching to endothelial cells, activating complement system causing cell lysis via the membrane-attack complex (MAC). This causes cell death and fewer capillaries in the muscle.

• #24 A Review of Myositis-Associated Interstitial Lung Disease

  https://www.mdpi.com/2077-0383/13/14/4055

  There is a well-established relationship between different subsets of idiopathic inflammatory myopathies (IIMs, myositis) and interstitial lung disease (ILD), with lung complications sometimes presenting prior to myopathic manifestations. […] The subtypes of myositis include those that are strongly associated with ILD, such as polymyositis (PM) and dermatomyositis (DM). […] Notably, there is a high prevalence of ILD associated with several MSAs, most strongly with anti-melanoma differentiate factor 5 (MDA5) and the anti-aminoacyl-tRNA synthetase antibodies (ASAb), which help to define antisynthetase syndrome (ASyS). […] The pathogeneses of PM and DM have considerable overlap and share important features. […] In PM and DM, skeletal muscle cells (myocytes) aberrantly express MHC class I receptors on their cell surface.

• #25 Diagnosis, pathogenesis and treatment of myositis: recent advances

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3927896/

  Cell stress appears to be a crucial component of the complex pathogenesis of IBM, as evidenced by co-localization of B-crystallin and APP/-amyloid. It has been suggested that, under proinflammatory conditions, inducible nitric oxide synthase is up-regulated and causes fibre death. […] Despite many recent studies and growing knowledge of the pathogenesis of myositis, our treatment of DM, PM and NM is still based more on experience than on prospective double-blind studies with an adequate number of patients. IBM remains a challenge due to its complex pathogenesis and lack of effective treatment.

• #26 Inclusion body myositis: clinical features and pathogenesis | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-019-0186-x

  Mounting evidence that IBM is an autoimmune T cell-mediated disease provides hope that future therapies directed towards depleting these cells could be effective. […] IBM has a greater range of autoimmune T cell abnormalities than any other muscle disease; treatment refractoriness has paradoxically given rise to the view that IBM is not an autoimmune disease. […] Treatment refractoriness probably reflects the inability of current therapies to inhibit or deplete the highly differentiated population of effector memory and terminally differentiated effector T cells present in IBM. […] Proposed pathogenetic cascade of inclusion-body myositis: importance of amyloid-, misfolded proteins, predisposing genes, and aging. […] Inclusion-body myositis: a myodegenerative conformational disorder associated with A, protein misfolding, and proteasome inhibition. […] Sporadic inclusion-body myositis: a degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy.

• #27 Role of Myokines in Myositis Pathogenesis and Their Potential to be New Therapeutic Targets in Idiopathic Inflammatory Myopathies – ScienceOpen

  https://www.scienceopen.com/document?vid=fd545b3f-e538-468b-ab15-2abc2f7e1d38

  Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of autoimmune diseases whose treatment is often a challenge. […] Therefore, other signaling pathways that could contribute to the pathogenesis of myositis have been investigated, such as the expression of myokines in skeletal muscle in response to the inflammatory process. […] In this review, we will refer to these muscle cytokines that are overexpressed or downregulated in skeletal muscle in patients with various forms of IIM, thus being able to contribute to the maintenance of the autoimmune process. […] Here, we consider the main myokines involved in the pathogenesis of myositis, expressing our view on the possibility of using them as potential therapeutic targets: interleukins IL-6, IL-15, and IL-18; chemokines CXCL10, CCL2, CCL3, CCL4, CCL5, and CCL20; myostatin; follistatin; decorin; osteonectin; and insulin-like 6.

• #28 Myositis Ossificans : Pathogenesis

  https://webpathology.com/images/orthopedic/tumor-like-lesions-of-bone/myositis-ossificans/40364

  The pathogenesis of myositis ossificans (MO) is incompletely understood. Most cases are related to trauma, which may be a recent episode of soft tissue trauma, repetitive minor trauma, or even unusual muscle exertion. The initial reparative fibroblastic/myofibroblastic response is followed by ossification. This is due to dysregulation of local stem cells at the site of injury which causes inappropriate differentiation of fibroblasts into osteoblasts. The mechanisms at play in nontraumatic cases are also unknown. MO has been seen in association with burns, paraplegia, and certain infections. Some cases with classic features of myositis ossificans harbor rearrangements of USP6 – a finding also seen in nodular fasciitis and soft tissue aneurysmal bone cyst.

• #29 Viral and retroviral myositis | MedLink Neurology

  https://www.medlink.com/articles/viral-and-retroviral-myositis

  Myositis is one of the complications of viral infections. Viral myositis is an illness characterized by muscle weakness and pain associated with elevated muscle enzyme levels and laboratory evidence of viral infection, ideally supported by detection of viral presence in the muscle. […] Both viruses and retroviruses are well-known pathogens that can be associated with inflammatory myopathy. Viral myositis results from direct infection of muscle or the ensuing inflammatory response. […] Certain infectious agents have been associated with idiopathic chronic inflammatory myopathies and might shed light on pathogenesis and offer practical treatment strategies. […] This became especially important in the 1990s when HIV and other retroviruses as well as hepatitis C virus were investigated for their role in polymyositis and inclusion body myositis.

• #30 Viral and retroviral myositis | MedLink Neurology

  https://www.medlink.com/articles/viral-and-retroviral-myositis

  The mechanisms of viral myositis are not fully elucidated, but there is evidence for several pathophysiological mechanisms. The virus-host interactions that contribute to myositis include: (1) direct infection (acute or chronic) or host response to viral antigens, (2) molecular mimicry, and (3) immune dysregulation. […] In most of the studies published to date, there was not enough evidence of direct viral invasion of the muscle fibers. […] However, in two cases of inflammatory myopathy associated with chronic hepatitis B infection, hepatitis B virus DNA and viral antigens were found inside intact muscle fibers. […] Although HIV, HTLV-1, and hepatitis C virus do not seem to cause persistent muscle infection, they do persist in many cells of the body and may cause muscle inflammation via several mechanisms: (1) immune cell activation, leading to cytokine and lymphokine release that may induce the expression of nontolerant antigens on muscle cells or (2) molecular mimicry.

• #31

  https://link.springer.com/article/10.1007/s11926-024-01164-7

  The pathogenesis of myositis is intricate, influenced by a complex interplay of environmental and genetic factors that collectively shape disease susceptibility. […] Recent advancements have increasingly associated the disease with the intracellular actions of pathogenic autoantibodies, disrupting the function of their specific autoantigens.

• #32

  https://journals.lww.com/ijru/fulltext/2020/15002/pathogenesis_of_muscle_weakness_in_inflammatory.5.aspx

  Major histocompatibility complex (MHC) is downregulated in myoblasts, myotubes, and mature muscle cells under healthy conditions. Immunohistochemical studies in myositis have shown widespread upregulation of MHC-I in muscle fibers. […] The current-day understanding of pathogenesis of muscle weakness in IIM suggests an initial microvascular and mitochondrial dysfunction followed by innate immune activation at the muscles which perpetuates the adaptive immune response. There are also several nonimmune mechanisms such as ER stress and UPR which act in tandem with aberrant immune response and resulting in muscle weakness. The muscle weakness is a direct result of damage to muscle fibers, impaired regeneration mechanisms, and decreased cross-bridge formation.

Zobacz więcej