scholarly journals THU0365 INCREASED HSP90 IN MUSCLE TISSUE AND PLASMA ASSOCIATES WITH DISEASE ACTIVITY AND SKELETAL MUSCLE INVOLVEMENT IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 414.1-414
Author(s):  
H. Štorkánová ◽  
S. Oreska ◽  
M. Špiritović ◽  
B. Heřmánková ◽  
O. Kryštůfková ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Disease Activity ◽  
Inflammatory Cells ◽  
Healthy Controls ◽  
Inflammatory Myopathies ◽  
Muscle Enzymes ◽  
Muscle Involvement ◽  
Hsp90 Expression ◽  
Muscle Biopsies ◽  
Skeletal Muscle Involvement

Background:Heat shock proteins (Hsps) are chaperones playing important roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cellsObjectives:The aim of our study was to assess Hsp90 expression in muscle biopsies and plasma of patients with idiopathic inflammatory myopathies (IIM) and to characterize its association with IIM-related features.Methods:Total of 277 patients with IIM (198 females, 79 males; mean age 54.8; disease duration 4.1 years; DM, 104/PM, 108/CADM, 31/IMNM, 25) and 157 healthy individuals (92 females, 65 males; mean age 47.0) were included in plasma analysis. Muscle biopsy samples (PM, DM, IMNM, myodystrophy, myasthenia gravis) were stained for Hsp90α (Thermo Fisher Scientific, USA) and Hsp90β (Abcam, UK). Plasma Hsp90 was measured by ELISA kit (eBioscience, Vienna, Austria). The cytokines/chemokines were analysed by using Bio-Plex ProTMhuman Cytokine 27-plex Assay (BIO-RAD, California, USA.Data are presented as median(IQR).Results:In muscle biopsies, Hsp90 expression of both subunits (alpha and beta) was higher in IIM than in controls. Increased Hsp90 was detected in perifascicular degenerating and regenerating fibers, inflammatory cells (DM, PM), and necrotic and regenerating fibers (IMNM). Plasma Hsp90 levels were increased in IIM patients compared to healthy controls (55.9 (46.9 – 62.5)vs 9.76(7.5 – 13.8), p<0.0001), and in individual subgroups of IIM vs. healthy controls (DM-22.01(14.1 – 41.2), PM-19.7(14.3 – 42.2), CADM-18.9(11.7 – 29.7), IMNM-19.6(16.3 – 45.5), p<0.0001 for all). Hsp90 was higher in males compared to females (p=0.040) and in patients with ILD (p=0.003), cardiac involvement (p=0.004), dysphagia (p=0.018) and presence of anti-Ro52 (p=0.036). Hsp90 levels in all patients positively correlated with muscle enzymes (Tab.1). Hsp90 was associated with disease activity and skeletal muscle involvement (Tab.1). Out of all clinical parameters listed in above-mentioned univariate analysis, in multiple regression analysis Hsp90 levels in IIM patients were significantly affected by muscle enzymes only (p<0.0001, β=0.345). Furthermore, Hsp90 positively correlated with some crucial cytokines involved in pathogenesis of myositis (Tab. 1).Tab 1Clinical parametersSpearman’s rp – valueLDH; AST; ALT0.554; 0.383; 0.181< 0.0001; < 0.0001; 0.003PtDGA; PhDGA; MITAX; MYOACT0.223; 0.217; 0.175; 0.159< 0.001; < 0.001; 0.004; 0.012Pulmonary disease activity0.2010.001Muscle disease activity0.1460.018MMT8, total score; m. biceps brachii; m. gluteus maximus; m. iliopsoas-0.126; -0.125; -0.159; -0.1430.042; 0.043; 0.011; 0.023MDI – Myositis damage index – severity0.1500.041Current Prednisone equivalent dose0.1830.006Cytokines:IL-1b; IL-2; IL-4; IL-6; IFN-γ0.188; 0.269; 0.190; 0.182; 0.2290.002; < 0.0001; 0.002; 0.003; < 0.0001Conclusion:We demonstrate increased Hsp90 expression in IIM muscle biopsy samples, specifically in inflammatory cells, degenerating, regenerating and/or necrotic fibers. Increased Hsp90 plasma levels in IIM patients are associated with disease activity and damage, and with the involvement of proximal skeletal muscles, heart and lungs.Acknowledgments:Supported by AZV-16-33542A, MHCR 023728 and SVV – 260373.Disclosure of Interests:Hana Štorkánová: None declared, Sabina Oreska: None declared, Maja Špiritović: None declared, Barbora Heřmánková: None declared, Olga Kryštůfková: None declared, Heřman Mann: None declared, Martin Komarc: None declared, Josef Zámečník: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiří Vencovský: None declared, Ladislav Šenolt: None declared, Michal Tomcik: None declared

A Case of Immune-Mediated Necrotizing Myopathy With Associated Skeletal Muscle Involvement by Sarcoid Granulomata: A Rare Association

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S69-S69
Author(s):  
Shalla Akbar ◽  
Sandhya Dasaraju ◽  
Osama Elkadi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Weakness ◽  
Inflammatory Myopathies ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Muscle Enzymes ◽  
Muscle Involvement ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Skeletal Muscle Involvement

Abstract Skeletal muscle involvement by noncaseating granulomata occurs in a variety of conditions, including sarcoidosis, infections, and rarely in association with primary inflammatory myopathies such as inclusion body myositis (IBM) and dermatomyositis (DM). Sarcoid myopathy is typically asymptomatic; however, a picture of acute myositis with proximal muscle weakness has been described. Immune-mediated necrotizing myopathy (IMNM) is a subgroup of inflammatory myopathies typically presenting with proximal muscle weakness and markedly elevated muscle enzymes, mostly occurring in the setting of statin treatment. IMNM is associated with positive autoantibodies, but a subset of cases is antibody negative. Here we describe a case of myopathy occurring in association with sarcoidosis with combined features of granulomatous and necrotizing myopathy. The patient was a 54-year-old African American male with medical history significant for statin use 3 years ago, which was discontinued due to myalgia and elevated muscle enzymes and biopsy-proven sarcoidosis diagnosed on a pulmonary lymph node biopsy. He presented with progressive worsening of bilateral proximal weakness involving the upper and lower extremities. Electromyogram showed features of active myopathy with no evidence of peripheral neuropathy. Myositis panel was negative for the following antibodies: anti-Jo1, Mi-2, anti-Ku, PL-7, PL-12, OJ, EJ, and SRP. However, there was elevation of aldolase, CRP, and CK-MB. Biopsy of thigh and deltoid muscle showed necrotic muscle fibers, myophagocytosis with associated minimal inflammation, and multiple well-formed nonnecrotizing granulomas with multinucleated giant cells. Myopathic features include increased internalized nuclei, round atrophic fibers, and scattered split fibers. Specific features of IBM or DM were not present. Conclusion Myopathies developing or worsening after discontinuation of statin are rare. The association of necrotizing myopathy with sarcoidosis is not well described in the literature. Additional studies are warranted to elucidate this association.

Alterations in activin A–myostatin–follistatin system associate with disease activity in inflammatory myopathies

Rheumatology ◽  
2020 ◽  
Vol 59 (9) ◽  
pp. 2491-2501 ◽  
Author(s):  
Lucia Vernerová ◽  
Veronika Horváthová ◽  
Tereza Kropáčková ◽  
Martina Vokurková ◽  
Martin Klein ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Disease Activity ◽  
Muscle Tissue ◽  
Activin A ◽  
Muscle Disease ◽  
Manual Muscle Testing ◽  
Healthy Controls ◽  
Inflammatory Myopathies ◽  
Muscle Testing ◽  
Tgf Β1

Abstract Objectives The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis. Methods A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-β1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR. Results We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = −0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls. Conclusion This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A–myostatin–follistatin system in muscle wasting diseases.

scholarly journals Antiangiogenic VEGF Isoform in Inflammatory Myopathies

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nila Volpi ◽  
Alessandra Pecorelli ◽  
Paola Lorenzoni ◽  
Francesco Di Lazzaro ◽  
Giuseppe Belmonte ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Western Blot ◽  
Inflammatory Cells ◽  
Human Muscle ◽  
Vascular Endothelial ◽  
Inflammatory Myopathies ◽  
Vegf Expression ◽  
Inflammatory Score ◽  
Endothelial Growth Factor ◽  
Muscle Biopsies

Objective. To investigate expression of vascular endothelial growth factor (VEGF) antiangiogenic isoformA-165bon human muscle in idiopathic inflammatory myopathies (IIM) and to compare distribution of angiogenic/antiangiogenic VEGFs, as isoforms shifts are described in other autoimmune disorders.Subjects and Methods. We analyzedVEGF-A165band VEGF-A by western blot and immunohistochemistry on skeletal muscle biopsies from 21 patients affected with IIM (polymyositis, dermatomyositis, and inclusion body myositis) and 6 control muscle samples. TGF-β, a prominent VEGF inductor, was analogously evaluated. Intergroup differences of western blot bands density were statistically examined. Endomysial vascularization, inflammatory score, and muscle regeneration, as pathological parameters of IIM, were quantitatively determined and their levels were confronted with VEGF expression.Results.VEGF-A165bwas significantly upregulated in IIM, as well as TGF-β. VEGF-A was diffusely expressed on unaffected myofibers, whereas regenerating/atrophic myofibres strongly reacted for both VEGF-A isoforms. Most inflammatory cells and endomysial vessels expressed both isoforms.VEGF-A165blevels were in positive correlation to inflammatory score, endomysial vascularization, and TGF-β.Conclusions. Our findings indicate skeletal muscle expression of antiangiogenicVEGF-A165band preferential upregulation in IIM, suggesting that modulation of VEGF-A isoforms may occur in myositides.

Skeletal muscle involvement in tropical spastic paraparesis/HTLV-1-associated myelopathy

1994 ◽  
Vol 17 (8) ◽  
pp. 923-930 ◽  
Author(s):  
Alberto Alain Gabbai ◽  
Clayton A. Wiley ◽  
Acary S. B. Oliveira ◽  
Ricardo Smith ◽  
Beny Schmidt ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Spastic Paraparesis ◽  
Tropical Spastic Paraparesis ◽  
Muscle Involvement ◽  
Skeletal Muscle Involvement

Relationship between Thyroid Function and Skeletal Muscle Involvement in Subclinical and Overt Hypothyroidism

2001 ◽  
Vol 11 (3) ◽  
pp. 217-221 ◽  
Author(s):  
Elisabeth Hartl ◽  
Josef Finsterer ◽  
Carmen Grossegger ◽  
Alois Kroiss ◽  
Claudia Stöllberger
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Function ◽  
Overt Hypothyroidism ◽  
Muscle Involvement ◽  
Skeletal Muscle Involvement

scholarly journals THU0358 NEGATIVE CHANGES OF BODY COMPOSITION IN MYOSITIS PATIENTS AND THEIR ASSOCIATION WITH DISEASE SPECIFIC CHARACTERISTICS, PHYSICAL ACTIVITY AND NUTRITIONAL STATUS.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 410.3-410
Author(s):  
S. Oreska ◽  
M. Špiritović ◽  
P. Česák ◽  
O. Marecek ◽  
H. Štorkánová ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Lipid Metabolism ◽  
Nutritional Status ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Disease Duration ◽  
Serum Levels ◽  
Muscle Involvement

Background:Skeletal muscle, pulmonary and articular involvement in idiopathic inflammatory myopathies (IIM) limit the mobility/self-sufficiency of patients, and can have a negative impact on body composition.Objectives:The aim was to assess body composition and physical activity of IIM patients and healthy controls (HC) and the association with selected inflammatory cytokines/chemokines and laboratory markers of nutrition and lipid metabolism.Methods:54 patients with IIM (45 females; mean age 57.7; disease duration 5.8 years; polymyositis (PM, 22) / dermatomyositis (DM, 25) / necrotizing myopathy (IMNM, 7)) and 54 age-/sex-matched HC (45 females, mean age 57.7) without rheumatic/tumor diseases were included. PM/DM patients fulfilled Bohan/Peter criteria for PM/DM. We assessed body composition (densitometry: iDXA Lunar, bioelectric impedance: BIA2000-M), physical activity (Human Activity Profile, HAP questionnaire), serum levels of 27 cytokines/chemokines (commercial multiplex ELISA kit, Bio-Rad Laboratories) and serum levels of selected parameters of nutrition and lipidogram. Disease activity (MITAX and MYOACT activity score) and muscle involvement (manual muscle testing, MMT-8, and functional index 2, FI2) were evaluated. Data are presented as mean±SD.Results:Compared to HC, patients with IIM had a trend towards significantly increased body fat % (BF%; iDXA: 39.9±7.1 vs. 42.4±7.1 %, p=0.077), but significantly decreased lean body mass (LBM; iDXA: 45.6±8.1 vs. 40.6±7.2 kg, p=0.001; BIA: 52.6±8.8 vs. 48.7±9.0 kg, p=0.023), increased extracellular mass/body cell mass (ECM/BCM) ratio (1.06±0.15 vs. 1.44±0.42, p<0.001), reflecting deteriorated nutritional status and predisposition for physical activity, and significantly lower bone mineral density (BMD: 1.2±0.1 vs. 1.1±0.1 g/cm2, p<0.001). Disease duration negatively correlated with BMD and LBM-BIA. Disease activity (MITAX, MYOACT) positively correlated with LBM (by BIA and DXA), similarly as with basal metabolic rate (BMR), and fat free mass (FFM). CRP was positively associated with BF% (BIA and DXA). Higher BF%-DEXA was associated with worse physical endurance (FI2) and worse ability to perform physical activity (HAP). MMT-8 score negatively correlated with ECM/BCM ratio. Serum levels of several inflammatory cytokines/chemokines (specifically IL-1ra, MCP, IL-10) and markers of nutrition (specifically albumin, C3-, C4-complement, cholinesterase, amylase, insulin and C-peptide, vitamin-D, orosomucoid), and lipid metabolism (specifically triglycerides, high-density lipoprotein, apolipoprotein A and B, atherogenic index of plasma) were significantly associated with alterations of body composition in IIM patients. (p<0.05 for all correlations)Conclusion:Compared to healthy age-/sex-matched individuals we found significant negative changes in body composition of our IIM patients associated with their disease activity and duration, inflammatory status, skeletal muscle involvement, and physical activity. These data could reflect their impaired nutritional status and predispositions for physical exercise, aerobic fitness and performance.Serum levels of certain inflammatory cytokines/chemokines and markers of nutrition and lipid metabolism were associated with alterations of body composition in IIM patients. This might further support the role of systemic inflammation and nutritional status on the negative changes in body composition of IIM patients.Acknowledgments:Supported by AZV NV18-01-00161A, MHCR 023728, SVV 260373 and GAUK 312218Disclosure of Interests:Sabina Oreska: None declared, Maja Špiritović: None declared, Petr Česák: None declared, Ondrej Marecek: None declared, Hana Štorkánová: None declared, Barbora Heřmánková: None declared, Kateřina Kubinova: None declared, Martin Klein: None declared, Lucia Vernerová: None declared, Olga Růžičková: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Ladislav Šenolt: None declared, Heřman Mann: None declared, Jiří Vencovský: None declared, Michal Tomčík: None declared

Skeletal muscle involvement in infantile systemic hyalinosis

2003 ◽  
Vol 7 (6) ◽  
pp. 401-406 ◽  
Author(s):  
Zarazuela Zolkipli ◽  
Cheryl Longman ◽  
Sue Brown ◽  
Nazneen Rahman ◽  
S.E Holder ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Involvement ◽  
Infantile Systemic Hyalinosis ◽  
Skeletal Muscle Involvement
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