Materiały źródłowe

• #1 Polymyositis and dermatomyositis: pathophysiology – PubMed

  https://pubmed.ncbi.nlm.nih.gov/21444017/

  Recent advances have increased the understanding of the pathogenesis of polymyositis and dermatomyositis. Clearly, the pathogenesis is complex, and adaptive (eg, autoimmune) and innate and nonimmune pathways play a role in the disease mechanisms, but the relative contribution may vary between patients and in different phases of the disease. […] Phenotyping patients using autoantibody profiling has resulted in information on molecular pathways that may be relevant in certain subsets of patients with polymyositis or dermatomyositis, but combining the autoantibody profiles with molecular signatures of innate and nonimmune mechanisms would enhance our ability to classify, diagnose, and treat these disorders more effectively.

• #2 Polymyositis and Dermatomyositis: Pathophysiology | Musculoskeletal Key

  https://musculoskeletalkey.com/polymyositis-and-dermatomyositis-pathophysiology/

  Recent advances have increased the understanding of the pathogenesis of polymyositis and dermatomyositis. Clearly, the pathogenesis is complex, and adaptive (eg, autoimmune) and innate and nonimmune pathways play a role in the disease mechanisms, but the relative contribution may vary between patients and in different phases of the disease. […] Immune (adaptive and innate) and nonimmune pathways play a role in the disease pathogenesis. The magnitude and exact nature of the contribution of these pathways to disease initiation and progression are still unclear. Understanding the relative contribution of these pathways is important to design rational therapies for these disorders. […] The role of B cells in the pathogenesis of polymyositis and dermatomyositis is supported by the presence of B cells and plasma cell infiltrates in the muscle tissue and that immunoglobulin transcripts are among the most abundant of the immune transcripts in the muscle tissue of patients with myositis.

• #3 Polymyositis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563129/

  Polymyositis, a relatively uncommon autoimmune disorder, develops due to abnormal activation of cytotoxic T lymphocytes (CD8 cells) and macrophages against muscular antigens that result in rhabdomyolysis and ultimately presents as a proximal myopathy. […] Polymyositis (PM), an autoimmune disorder, develops due to abnormal activation of cytotoxic T lymphocytes (CD8 cells) and macrophages against muscular antigens as well as the strong extrafusal muscular expression of major histocompatibility complex 1, causing damage to the endomysium of skeletal muscles. […] Pathophysiological mechanisms have been proposed to define the main reason for rhabdomyolysis in polymyositis. Direct damage is caused by the cellular immune response that develops as a result of abnormal activation of cytotoxic T cells (CD8) and macrophages, with some involvement of type B lymphocytes and dendritic cells. Indirectly, damage can happen due to the release of inflammatory mediators in circulation by the cells such as cytokines and interleukins. A study reported a significant increase in pro-inflammatory cytokine IL-21, both in the muscle and serum of affected patients, along with the increased expression of IL-21 receptors (IL-21R) in damaged muscle fibers in these patients.

• #4 Polymyositis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/335925-questions-and-answers

  The pathogenesis of polymyositis appears to be a T-cellmediated cytotoxic process directed against unidentified muscle antigens. Supporting this conclusion is the involvement of CD8 T cells, which, along with macrophages, initially surround healthy nonnecrotic muscle fibers and eventually invade and destroy them. […] The factors triggering a T-cellmediated process in polymyositis are unclear. Viruses have been implicated; so far, however, the only viruses that have been etiologically connected with the disease are the human retroviruses human immunodeficiency virus (HIV) and human T-cell lymphotrophic virus type I (HTLV-I), the simian retroviruses, and coxsackievirus B. Those viruses may directly invade the muscle tissue, damaging the vascular endothelium and releasing cytokines, which then induce abnormal expression of the major histocompatibility complex (MHC) and render the muscle susceptible to destruction.

• #5 A Case of Refractory Polymyositis Successfully Treated With Abatacept Monotherapy | Volume 35 – Issue 4 – December 2020 | Archives of Rheumatology

  https://archivesofrheumatology.org/full-text/1127

  Polymyositis (PM) is an autoimmune disease progressing in the form of a break down of the muscles that is induced by chronic inflammation in skeletal muscles. […] Although its etiology is unknown, the most commonly acknowledged hypothesis is the destruction of muscle fibers mediated by T lymphocytes. […] Biopsy findings are characterized by a dense infiltration of muscle fibers by inflammatory cells composed mostly of CD8+ T cells and macrophages and the damage arising from such infiltration. […] T lymphocytes are observed to play a key role in both the onset and the persistence of inflammation in PM. This observation leads to the consideration that abatacept may be effective in the treatment of this disease as it is a recombinant CTLA4-Ig fusion protein that provides for the inhibition of T lymphocyte costimulation.

• #6 Polymyositis – Wikipedia

  https://en.wikipedia.org/wiki/Polymyositis

  Polymyositis is an inflammatory myopathy mediated by cytotoxic T cells with an as yet unknown autoantigen, while dermatomyositis is a humorally mediated angiopathy resulting in myositis and a typical dermatitis. […] The cause of polymyositis is unknown and may involve viruses and autoimmune factors. Cancer may trigger polymyositis and dermatomyositis, possibly through an immune reaction against cancer that also attacks a component of muscles.

• #7 Inflammatory myopathies

  https://neuropathology-web.org/chapter13/chapter13fInflammatory.html

  Inflammatory myopathies (IMs) are acquired, treatable autoimmune diseases, characterized clinically by weakness and soreness of muscles and elevated CK and pathologically by myonecrosis and mononuclear inflammatory infiltrates. […] Polymyositis is now thought to be rare and is diagnosed by exclusion of other IMs. It affects predominantly adults who present with proximal weakness (without a rash), developing over a period of weeks or months. The muscle biopsy shows endomysial mononuclear cells and myonecrosis. PM is a cell-mediated autoimmune disorder in which cytotoxic (CD8-positive) lymphocytes and macrophages invade and destroy myofibers. The inflammatory cells are in the endomysium (between and around individual myofibers.) Inflammation may be focal and the MRI is useful in identifying affected areas for biopsy. […] The pathogenesis of IBM is not known but probably involves abnormal protein processing associated with ageing of myofibers, and the deposition of toxic protein polymers that damage myofibers and trigger inflammation.

• #8

  https://journals.lww.com/ijd/fulltext/2012/57050/polymyositis_and_dermatomyositis__disease_spectrum.6.aspx

  Polymyositis (PM) and Dermatomyositis (DM) are autoimmune myopathies characterized by inflammation and weakness of proximal muscles with extra muscular manifestations. […] Involvement of skin is the primary clinical feature, which distinguishes DM from PM. […] From the immunological point of view these two diseases are different. Dermatomyositis is humorally mediated disease whereas polymyositis is T cell mediated disease. […] In PM the characteristic feature is presence of CD8 + T cells and macrophages in the myofibers. […] The expression of MHC-I on myositis muscle suggest that these cells may be killed by CD8 + T cells which contain perforin, a pore-forming protein that mediates the entry of cytotoxic proteases and calcium into target cells. […] Although MHC-I has been proposed to mediate cell death in PM, but it is also expressed in DM patients mainly on perifascicular fibers.

• #9 Polymyositis and dermatomyositis overview – wikidoc

  https://www.wikidoc.org/index.php/Polymyositis_and_dermatomyositis_overview

  The exact pathogenesis of polymyositis and dermatomyositis is not fully understood. However, it is understood that polymyositis and dermatomyositis are the result of autoimmune attack but triggering factors are not well-known. […] Polymyositis is caused by inflammation and degeneration of the muscles. In polymyositis, CD8-positive cytotoxic T cells invade muscle fibers that express MHC class I antigens which may leads to fiber necrosis via the perforin pathway. […] In dermatomyositis, activation and deposition of complements may lead to lysis of endomysial capillaries and muscle ischemia. […] Genes including HLA DRB1*0301 and HLA DQA1*0501 alleles, and tumour necrosis factor 308A might be associated with development of polymyositis and dermatomyositis, especially in familial cases. […] The key pathological change of dermatomyositis is a vasculitis, which involves endomysial and perimysial capillaries and arterioles. This vasculitis begins with endothelial swelling and is followed by endothelial necrosis and capillary loss. […] The vasculitis is thought to be caused by circulating anti-endothelial antibodies. Interaction of these antibodies with vascular antigens activates complement, leading to formation of the membranolytic attack complex (MAC), which destroys endothelial cells.

• #10

  https://journals.lww.com/ijd/fulltext/2012/57050/polymyositis_and_dermatomyositis__disease_spectrum.6.aspx

  In one study Fasth et al. have reported that in muscles of patients of PM and DM, the main effector T-cell subset is CD28null T-cells, which are resistant to apoptosis and thus may be responsible for recurrence of disease following treatment. […] It has also been shown that in DM patients there is increase in Ki-67 positive keratinocytes and decreased number of Bcl-2 positive cells in the basal layer of epidermis suggesting increase proliferation and abnormal apoptotic pathway in skin of DM patients. […] The exact role of these auto-antibodies in the disease pathology is not clear. […] In one study by Stone et al. it has been found that in 81 patients with positive anti-Jo-1, there was modest correlation between auto-antibody titer, creatinine kinase level, muscle and lung involvement.

• #11 Polymyositis and Dermatomyositis: Novel Insights into the Pathogenesis and Potential Therapeutic Targets – Arash H Lahouti – Discovery Medicine

  https://www.discoverymedicine.com/Arash-H-Lahouti/2015/06/polymyositis-and-dermatomyositis-novel-insights-into-the-pathogenesis-and-potential-therapeutic-targets/

  Current literature supports both autoimmune and non-immune mediators of muscle damage in both polymyositis and dermatomyositis. However, the exact contribution of each pathway to the muscle damage is still unclear. Traditionally, muscle damage in dermatomyositis is believed to be mediated by humoral factors (antibodies and complement system) directed against endomysial capillary endothelial cells. In contrast, a cytotoxic T cell-mediated muscle fiber injury is perceived to be the predominant mechanism in polymyositis. […] Evidence supporting the role of B cells in the pathogenesis of myositis arises from the frequent presence of myositis-specific autoantibodies (MSAs) in PM and DM patients. […] Recent studies have shown that the majority of CD4+ and CD8+ lymphocytes infiltrating myositis muscle are lacking co-stimulatory molecule CD28. It is postulated that CD28 down-regulation occurs as a result of decreased transcription.

• #12 Immune mechanisms in the pathogenesis of idiopathic inflammatory myopathies | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar2139

  Damage or activation of blood vessels could indicate that the microvessels are targets of the immune reaction in some subsets of patients with IIM. […] One such non-immune mechanism, endoplasmic reticulum stress, has been proposed, on the basis of observations both from human studies and from an animal model for myositis, the major histocompatibility complex (MHC) class I transgene. […] The presence of granulysin-expressing CD8+ T lymphocytes tended to correlate with steroid resistance in polymyositis. […] A role for B lymphocytes as well as one for CD4+ T lymphocytes in the pathogenesis of IIMs is supported by frequently detected autoantibodies in polymyositis and dermatomyositis but less often in inclusion-body myositis. […] These autoantibodies are both non-specific (frequently also being found in other autoimmune disease) and myositis-specific. […] A role for CD4+ T lymphocytes in the disease mechanism is further supported by the genetic association with HLA-DRB1*0301, DQA1*0501, and DQB1*0201, which was particularly seen for subgroups of patients with autoantibodies.

• #13 Polymyositis & Dermatomyositis – Free Sketchy Medical Lesson

  https://www.sketchy.com/medical-lessons/polymyositis-dermatomyositis

  The pathogenesis of polymyositis begins with increased expression of MHC I on the sarcolemma of striated muscle cells. This allows autoantigens to be presented to CD8+ cytotoxic T-cells, thus setting off the cascade leading to muscle fiber destruction. […] In polymyositis, there’s an increased expression of MHC I on the sarcolemma, leading to the activation of CD8+ cytotoxic T cells that initiate myofiber destruction, with muscle biopsies showing endomysial inflammatory infiltrate.

• #14 Polymyositis and Dermatomyositis: Pathophysiology | Musculoskeletal Key

  https://musculoskeletalkey.com/polymyositis-and-dermatomyositis-pathophysiology/

  The endomysial inflammatory infiltrates contain a high percentage of activated CD8 + T lymphocytes, macrophages, and CD4 + T lymphocytes. […] The authors and other researchers have shown that overexpression of MHC class I on muscle fibers of patients with myositis and the transgenic mouse model of myositis results in activation of the nuclear factor (NF)-B and ER stress response pathways. […] Thus, MHC class I expression in the skeletal muscle links the classic immune (through CD8 T cells) and nonimmune (ER stress) mediated mechanisms of muscle impairment and damage. […] The mechanisms that cause muscle fiber degeneration or muscle atrophy have not been clarified, and both cytotoxic cell death and an effect of disuse or a negative effect of glucocorticoids have been suggested.

• #15 Polymyositis and Dermatomyositis: Novel Insights into the Pathogenesis and Potential Therapeutic Targets – Arash H Lahouti – Discovery Medicine

  https://www.discoverymedicine.com/Arash-H-Lahouti/2015/06/polymyositis-and-dermatomyositis-novel-insights-into-the-pathogenesis-and-potential-therapeutic-targets/

  Given the inconsistent presence of IL-2, the most important T cell growth factor, it is thought that IL-15 is responsible for proliferation of T cells in myositis muscle. […] A variety of inflammatory cytokines are strongly expressed in IIMs. The cellular sources of these cytokines include adaptive immune system cells (CD4+ and CD8+ T lymphocytes, and B lymphocytes), macrophages, dendritic cells, mast cells, and regenerating muscle cells. […] Several studies have demonstrated increased expression of TLRs in muscle biopsies from myositis patients. […] HMGB1 may have a dual role in the pathogenesis of myositis. This protein acts through TLR-4 receptor to up-regulate MHC class I expression in muscle fibers. […] There is growing evidence that several non-immune mechanisms may be involved in the pathogenesis of inflammatory myopathies. A common feature on muscle biopsies from patients with myositis is overexpression of MHC class I. […] Recent studies provide evidence that multiple immune and non-immune mechanisms are involved in the pathophysiology of inflammatory myopathies. However, the contribution of each pathway to the pathogenesis may depend on the specific subset of IIM.

• #16 Polymyositis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563129/

  In addition to causing direct damage, certain cytokines such as IL-1alpha and IL-17 also upregulate the nuclear factor kappa B signaling pathway to increase major histocompatibility complex 1 class expression. NF-kappaB also damages myofibrils by affecting the myocytes’ differentiating ability negatively. […] Other possible pathological causes for polymyositis include damage to vascular endothelium leading to extravasation of inflammatory mediators from circulation as well as the involvement of humoral immune response depending on the presence of certain antibodies.

• #17

  https://link.springer.com/article/10.1007/s004010000207

  Polymyositis (PM) is a cell-mediated autoimmune disease. Perforin (PF), Fas ligand (FasL) and TNF- are considered to be important factors in cytotoxic T lymphocyte-mediated cell injury, and several studies have established a role of lymphotoxin (LT) in T helper type 1 (Th1)-induced cell-mediated autoimmune diseases. […] Our results indicated that the expression of LT was up-regulated in PM, and LT plays an important role in muscle injury and orchestrating the inflammatory reaction in PM.

• #18 Polymyositis and dermatomyositis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Polymyositis_and_dermatomyositis_pathophysiology

  The exact pathogenesis of polymyositis and dermatomyositis is not fully understood. However, it is understood that polymyositis and dermatomyositis are the result of autoimmune attack but triggering factors are not well-known. […] Polymyositis is caused by inflammation and degeneration of the muscles. In polymyositis, CD8-positive cytotoxic T cells invade muscle fibers that express MHC class I antigens which may lead to fiber necrosis via the perforin pathway. Hypoxia may reduce creatine phosphate and adenosine triphosphate (ATP) levels in muscle and lead to fatigue and muscle weakness. […] Interleukin (IL) 21, tumor growth factor-b (TGF-b), and high-mobility group protein 1 (HMG-1) induce muscle fatigue by decreasing Ca release. […] In dermatomyositis, activation and deposition of complements may lead to lysis of endomysial capillaries and muscle ischemia.

• #19 Idiopathic inflammatory myopathy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/idiopathic-inflammatory-myopathy/

  Idiopathic inflammatory myopathy is thought to arise from a combination of genetic and environmental factors. […] Researchers have identified variations in several genes that may influence the risk of developing idiopathic inflammatory myopathy. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. […] Specific variations of several HLA genes seem to affect the risk of developing idiopathic inflammatory myopathy. […] It is likely that specific genetic variations increase a person’s risk of developing idiopathic inflammatory myopathy, and then exposure to certain environmental factors triggers the disorder.

• #20 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

  The cause of idiopathic inflammatory myopathy seems to be an autoimmune reaction to muscle tissue in genetically susceptible people. […] For example, the alleles of the 8.1 ancestral haplotype (HLA-DRB1*03-DQA1*05-DQB1*02) increase risk of polymyositis, dermatomyositis, and interstitial lung disease. […] 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. […] Polymyositis and dermatomyositis can often be distinguished by muscle biopsy. In polymyositis, histology is usually characterized by predominant endomysial CD8+ T cell infiltrates without vasculopathy, whereas in dermatomyositis, histology is characterized by perifascicular B cell-predominant infiltrates with perivascular inflammation.

• #21 Myositis – Polymyositis and Dermatomyositis – Patient.info

  https://patient.info/doctor/myositis-polymyositis-and-dermatomyositis

  Polymyositis and dermatomyositis have an autoimmune basis. […] Viral infection has been implicated in the form of the human retroviruses HIV and human T-cell lymphotropic virus type I (HTLV-I), the simian retroviruses, and Coxsackievirus B. […] Polymyositis produces muscle weakness. […] The diagnosis is established by electromyography (EMG) and is confirmed by muscle biopsy. In polymyositis it is the definitive test. […] Polymyositis and dermatomyositis may be associated with other autoimmune diseases such as myasthenia gravis, Hashimoto’s thyroiditis, systemic sclerosis and Waldenstrm’s macroglobulinaemia. […] Myositis is associated with an increased risk of malignancy, particularly within three years of initial diagnosis. Dermatomyositis appears to have the strongest association with malignancy.

• #22 Microorganisms in Pathogenesis and Management of Dermatomyositis (DM) and Polymyositis (PM) | SpringerLink

  https://link.springer.com/chapter/10.1007/978-981-19-1946-6_23

  As with most autoimmune diseases, the etiology and especially the prime mover of idiopathic inflammatory myopathies are not well defined. It is assumed that the disease is related to a chronic immune impairment, following exposure to environmental agents in genetically predisposed individuals. […] In this chapter we discuss the role of microorganisms in pathogenesis of myopathies, especially polymyositis and dermatomyositis. We focused on interaction between immune response and biological and molecular networks created by host characteristics and most common pathogens as described in the literature on the topic. Infectious agents proved a strong connection with autoimmune myositis in several animal models, and, learning from the infamous recent zoonosis which started the SARS-CoV-2 (the autoimmune virus) pandemic, new challenges and discoveries are around the corner.

• #23 Dermatomyositis, Polymyositis and Necrotizing Myopathy – The Myositis Association

  https://www.myositis.org/research/tma-grants-fellowships/tma-funded-projects/dermatomyositis-polymyositis-and-necrotizing-myopathy/

  A pilot study grant of $200,000 has been provided to Kanneboyina Nagaraju, DVM, PhD of Binghamton University in New York. Dr. Nagarahus research will focus on inflammatory muscle changes seen in Dermatomyositis and Polymyositis and their similarity to those seen in viral infections. The study will evaluate whether this inflammation can be blocked using viral proteins. If successful, it could open up a new strategy for potential treatments. […] The aim of our study is to analyze the way in which these new cancer treatments cause myositis. This understanding is important in order to find new treatments for this new entity, since the usual treatments for myositis may not be effective and they may adversely affect the cancer treatment. […] This research project aims to test for differential gene expression in individuals with myositis-ILD in order to discover what abnormal processes within the lungs may be causing the disease. This will develop a better understanding of the molecular basis of myositis-ILD, which will help identify potential targets for drug treatments.

• #24 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.

• #25 AB0201 Altered Serum Fatty Acid Profiles in Patients with Polymyositis or Dermatomyositis Compared to Healthy Individuals and in Relation to Immunosuppressive Treatment | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/74/Suppl_2/958.1

  Polymyositis (PM) and dermatomyositis (DM) are chronic autoimmune diseases, characterized by muscle fatigue and low muscle endurance. Histopathological characteristics of muscle biopsies are infiltration of inflammatory cells, muscle fiber degeneration and regeneration. […] Our group has recently found that immunosuppressive treatment has significant effects on gene expression related to lipid and fatty acid (FA) metabolism that may contribute to the persistent muscle weakness often seen in myositis patients. Lipid dysregulation might lead to generation of lipotoxic mediators which contribute to cell dysfunction or death. Furthermore, a number of studies have confirmed the important effects of FA on skeletal muscle growth, strength and inflammation. However the involvement of lipids and FA in the pathogenesis of polymyositis and dermatomyositis has not been clarified.

• #26 AB0201 Altered Serum Fatty Acid Profiles in Patients with Polymyositis or Dermatomyositis Compared to Healthy Individuals and in Relation to Immunosuppressive Treatment | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/74/Suppl_2/958.1

  Our preliminary results suggest that FA composition of total serum lipids was different in myositis patients compared to healthy donors; the levels of palmitic16:0 acid was significantly higher (0.05) in myositis patients whereas the levels of arachidonic 20:4 (n-6) acid was significantly lower (p=0.05). Immunosuppressive treatment did not affect the total levels of lipid classes in the serum from myositis patients. However, the levels of phosphatidylcholine (PC) PC (32:1), phosphatidylethanolamine (PE) PE (36:5) and lysophosphatidylcholine (LPC) LPC (16:1) were all significantly higher (p0.05) in myositis patients after 6 months of immunosuppressive treatment. […] FA composition of total serum lipids is altered in myositis patients compared to healthy controls. Immunosuppressive treatment resulted in changed FA composition of serum PC, PE and LPC. These findings indicate that FA metabolism might be deregulated in PM and DM patients and may be further affected by immunosuppressive treatment.

• #27 Dermatomyositis, Polymyositis and Necrotizing Myopathy – The Myositis Association

  https://www.myositis.org/research/tma-grants-fellowships/tma-funded-projects/dermatomyositis-polymyositis-and-necrotizing-myopathy/

  There is increasing evidence that certain immune system cells called B cells are involved in the development of IIM, and that IIM B cells are abnormal. The purpose of this project is to better understand the immune mechanisms of IIM by studying how B cells from IIM patients function differently from healthy B cells. […] It has been shown that signals from the immune system, called type I interferons, reduce the ability of muscle cells to generate energy via mitochondria. It has also been shown that when muscle cells cant generate enough energy, they arent able to repair themselves after damage. The weakness and poor ability to repair damage to muscles seen in myositis may be due to these interferons reducing the capacity of muscle cells to produce energy via mitochondria. […] This study attempted to understand how muscle inflammation causes weakness, speculating that a loss of small blood vessels in the muscles leads to low oxygenation in muscle tissue and loss of muscle strength.

• #28 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. […] Understanding the relative contributions of each of these pathways to disease pathogenesis would help us to identify suitable drug targets to alleviate muscle damage and also improve muscle weakness and quality of life for patients suffering from these debilitating muscle diseases.

• #29 YKL-40-mediated Inflammatory Pathogenesis Common to Polymyositis / Dermatomyositis – ACR Meeting Abstracts

  https://acrabstracts.org/abstract/ykl-40-mediated-inflammatory-pathogenesis-common-to-polymyositis-dermatomyositis/

  YKL-40 is a chitinase-like protein that is associated with interstitial lung disease in patients with polymyositis (PM)/dermatomyositis (DM) but not with myositis. […] Here, we investigated whether YKL-40 is associated with PM/DM and assessed its role in PM/DM pathogenesis. […] Age-corrected serum YKL-40 values were significantly increased in patients with PM/DM compared to the HC but significantly decreased before and after treatment. […] Immunohistochemical analysis showed infiltration of YKL-40-positive inflammatory cells in the endomysium and perimysium of the muscle sheath. […] CD8+ and CD4+ T cells are believed to play predominant roles in muscle destruction in PM and DM, respectively. However, YKL-40-positive macrophages observed in both diseases suggest that cells other than CD8+ and CD4+ T cells may cause inflammation. This provides new insights to understand pathophysiological mechanisms of atypical myositis.

• #30 Meta-Analysis of Polymyositis and Dermatomyositis Microarray Data Reveals Novel Genetic Biomarkers

  https://www.mdpi.com/2073-4425/10/11/864

  Polymyositis (PM) and dermatomyositis (DM) are both classified as idiopathic inflammatory myopathies. […] Previous studies have indicated that these diseases present aspects of an auto-immune disorder; however, their exact pathogenesis is still unclear. […] The up-regulated genes were significantly enriched in interferon-signaling pathways in protein secretion, and/or in unfolded-protein response. […] We detected 10 single nucleotide polymorphisms (SNPs) which could potentially play key roles in driving the PM and DM. […] Previous studies demonstrated that there is a relationship between the muscle lesion and auto-antibodies and muscle-infiltrating immune cells. […] The importance of genetic variants in gene expression has been emphasized. […] This study is the first meta-analysis to combine multiple microarray datasets from different studies on the two diseases.

• #31 A key mechanism is discovered in Idiopathic Inflammatory Myopathies

  https://www.clinicbarcelona.org/en/news/a-key-mechanism-is-discovered-in-idiopathic-inflammatory-myopathies

  Researchers from the Clnic-IDIBAPS have taken part in a study that provides new information on the mechanisms involved in idiopathic inflammatory myopathies (IIM), a group of minority diseases that affect the muscles. […] The researchers showed that the antibodies can enter the muscle cells and accumulate in specific areas, where they can interfere with the normal cell functions. […] In cell culture, they observed that, when antibodies enter muscle cells, the effects observed were similar to those seen in patients, confirming that antibodies can directly cause dysfunction.

• #32 A Case of Refractory Polymyositis Successfully Treated With Abatacept Monotherapy | Volume 35 – Issue 4 – December 2020 | Archives of Rheumatology

  https://tjr.org.tr/full-text/1127

  The preferred management of PM has traditionally been with corticosteroids; however, some patients require adjunctive immunosuppressive agents because of insufficient response to glucocorticoids. The administration of abatacept monotherapy in patients with PM may be considered as a treatment option because it allows for monotherapy in patients with PM that cannot be managed with biological or other immunosuppressive agents and develop adverse effects because of corticosteroids. […] In conclusion, abatacept monotherapy can safely be used in patients with PM that do not respond to conventional treatment or develop treatment-related complications, with due consideration given to the pathogenesis of the disease and the action mechanism of the agent.

• #33 Considering IVIG for Polymyositis? Here’s What You Need to Know – AmeriPharma® Specialty Care

  https://ameripharmaspecialty.com/ivig/considering-ivig-for-polymyositis-heres-what-you-need-to-know/

  The exact mechanism of action is not fully understood. In polymyositis, white blood cells enter into and destroy the muscle fibers. IVIG suppresses these cells and helps improve your symptoms. Researchers believe IVIG may also work in other ways, such as by: […] Boosting your immune system […] Keeping your body from making large amounts of autoantibodies (proteins that destroy muscle fibers) […] Blocking the action of pro-inflammatory molecules […] Neutralizing molecules that trigger inflammation.

• #34 Myositis – Polymyositis and Dermatomyositis – Patient.info

  https://patient.info/doctor/myositis-polymyositis-and-dermatomyositis

  Although immunosuppressive and immunomodulatory therapies are frequently used, the optimal therapeutic regimen remains unclear. […] There is a lack of high-quality studies that assess the efficacy and toxicity of immunosuppressants in inflammatory myositis. […] Anti-155/140 antibody is associated with malignancy.

• #35 Polymyositis and Dermatomyositis: Novel Insights into the Pathogenesis and Potential Therapeutic Targets – Arash H Lahouti – Discovery Medicine

  https://www.discoverymedicine.com/Arash-H-Lahouti/2015/06/polymyositis-and-dermatomyositis-novel-insights-into-the-pathogenesis-and-potential-therapeutic-targets/

  Polymyositis (PM) and dermatomyositis (DM) are the two major forms of inflammatory muscle diseases. They are characterized clinically primarily by proximal muscle weakness. The disease mechanisms that cause muscle damage and dysfunction are not fully understood. However, because of the association with other autoimmune diseases, the presence of autoantibodies, and response to immunosuppressive medication, they are believed to be autoimmune in origin. Recent studies have highlighted the importance of the innate immune system and non-immune mechanisms and described novel adaptive immune-based pathways in the pathogenesis of polymyositis and dermatomyositis. […] Stimulation of Toll-like receptors (TLRs) by endogenous antigens, e.g., aminoacyl-tRNA synthetase enzyme, may trigger activation of signaling pathways and thereby induces expression of multiple genes involved in the inflammatory response. High-mobility group box-1 (HMGB1) might interact with the same receptors and cause skeletal muscle inflammation. In addition, this protein may be involved in T lymphocyte survival in muscle tissue. A newly described T cell subset, CD28- T cells, may have strong myotoxic properties and comprises the predominant muscle-infiltrating T cell phenotype. Future studies should focus more on understanding the relative contribution of each pathway to the pathogenesis of inflammatory myopathies. Given the connections between the pathways, targeting multiple pathways through combination therapies may be beneficial.

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