Plasma Myokine Profiles in Patients With AChRand MuSK-Ab-Positive Myasthenia Gravis
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background and Purpose Myokines include cytokines secreted by muscle fibers, which are the final targets of myasthenia gravis (MG). This pilot study investigated whether myokine plasma concentrations are altered in patients with MG and assessed the association between the concentration of each myokine and disease severity. Methods We compared the plasma concentrations of 15 myokines in 63 patients with acetylcholine receptor antibody (Ab)-positive MG and 14 with muscle-specific tyrosine kinase Ab-positive MG (MuSK MG) with those in 15 healthy controls. Plasma myokine concentrations were measured using a Luminex multiplex assay kit with magnetic beads that contained Abs for 15 myokines. Correlations between myokine concentration and clinical scale results were analyzed. Results The concentration of fractalkine in plasma was higher in MG (median [interquartile range]=419.6 [38.7–732.5] pg/mL) than in controls (158.5 [0.0–313.2] pg/mL, p=0.034). The leukemia inhibitory factor concentration was also found to be higher in MuSK MG (29.9 [8.7–40.1] pg/mL) than in healthy controls (7.6 [0.0–15.6] pg/mL, p=0.013). Fatty-acid-binding protein 3 (FABP3) concentrations in plasma were positively associated with clinical parameters for MG severity, including scores on the Quantitative Myasthenia Gravis score (p= 0.008), Myasthenia Gravis Activities of Daily Living (p=0.003), and Myasthenia Gravis Composite (p=0.024) scales. FABP3 concentration in plasma tended to decrease after treatment in patients without additional relapse but increased in those with further relapse. Conclusions The plasma myokine profile was significantly altered in patients with MG. FABP3 concentration may be useful in assessing disease severity and predicting the treatment response.
Abstract
Background and Purpose Myokines include cytokines secreted by muscle fibers, which are the final targets of myasthenia gravis (MG). This pilot study investigated whether myokine plasma concentrations are altered in patients with MG and assessed the association between the concentration of each myokine and disease severity. Methods We compared the plasma concentrations of 15 myokines in 63 patients with acetylcholine receptor antibody (Ab)-positive MG and 14 with muscle-specific tyrosine kinase Ab-positive MG (MuSK MG) with those in 15 healthy controls. Plasma myokine concentrations were measured using a Luminex multiplex assay kit with magnetic beads that contained Abs for 15 myokines. Correlations between myokine concentration and clinical scale results were analyzed. Results The concentration of fractalkine in plasma was higher in MG (median [interquartile range]=419.6 [38.7–732.5] pg/mL) than in controls (158.5 [0.0–313.2] pg/mL, p=0.034). The leukemia inhibitory factor concentration was also found to be higher in MuSK MG (29.9 [8.7–40.1] pg/mL) than in healthy controls (7.6 [0.0–15.6] pg/mL, p=0.013). Fatty-acid-binding protein 3 (FABP3) concentrations in plasma were positively associated with clinical parameters for MG severity, including scores on the Quantitative Myasthenia Gravis score (p= 0.008), Myasthenia Gravis Activities of Daily Living (p=0.003), and Myasthenia Gravis Composite (p=0.024) scales. FABP3 concentration in plasma tended to decrease after treatment in patients without additional relapse but increased in those with further relapse. Conclusions The plasma myokine profile was significantly altered in patients with MG. FABP3 concentration may be useful in assessing disease severity and predicting the treatment response.
참고문헌 (55)
- Feferman T, "Overexpression of IFN-induced protein 10 and its receptor CXCR3in myasthenia gravis", J Immunol, 174, pp.5324~5331 (2005)
- Garcia YR, "Acetylcholine receptorreactive antibody induces nitric oxide production by a rat skeletal muscle cell line : influence of cytokine environment", J Neuroimmunol, 120, pp.103~111 (2001)
- Li H, "Cytokine and chemokine mRNA expressing cells in muscle tissues of experimental autoimmune myasthenia gravis", J Neurol Sci, 161, pp.40~46 (1998)
- Maurer M, "IL-6 and Akt are involved in muscular pathogenesis in myasthenia gravis", Acta Neuropathol Commun, 3, pp.1~ (2015)
- Zhu D, "Lipid rafts serve as a signaling platform for nicotinic acetylcholine receptor clustering", J Neurosci, 26, pp.4841~4851 (2006)
- Iwasa K, "Caveolin-3 is aberrantly expressed in skeletal muscle cells in myasthenia gravis", J Neuroimmunol, 301, pp.30~34 (2016)
- Iwasa K, "Increased skeletal muscle expression of the endoplasmic reticulum chaperone GRP78 in patients with myasthenia gravis", J Neuroimmunol, 273, pp.72~76 (2014)
- Attia M, "Muscle satellite cells are functionally impaired in myasthenia gravis : consequences on muscle regeneration", Acta Neuropathol, 134, pp.869~888 (2017)
- Lee JH, "Role of myokines in regulating skeletal muscle mass and function", Front Physiol, 10, pp.42~ (2019)
- Covington JD, "Myokine expression in muscle and myotubes in response to exercise stimulation", Med Sci Sports Exerc, 48, pp.384~390 (2016)
- 소병훈, "Exercise-induced myokines in health and metabolic diseases", Integrative Medicine Research, 3(4), pp.172~179 (2014), 한국한의학연구원[DOI]
- Hutchinson KA, "Examination of the myokine response in pregnant and nonpregnant women following an acute bout of moderate-intensity walking", Front Physiol, 10, pp.1188~ (2019)
- Aoi W, "A novel myokine, secreted protein acidic and rich in cysteine(SPARC), suppresses colon tumorigenesis via regular exercise", Gut, 62, pp.882~889 (2013)
- Fontes-Oliveira CC, "A differential pattern of gene expression in skeletal muscle of tumor-bearing rats reveals dysregulation of excitation–contraction coupling together with additional muscle alterations", Muscle Nerve, 49, pp.233~248 (2014)
- Vernerová L, "Alterations in activin A-myostatin-follistatin system associate with disease activity in inflammatory myopathies", Rheumatology(Oxford), 59, pp.2491~2501 (2020)
- Jørgensen LH, "Secreted protein acidic and rich in cysteine(SPARC)in human skeletal muscle", J Histochem Cytochem, 57, pp.29~39 (2009)
- Mageriu V, "Role of myokines in myositis pathogenesis and their potential to be new therapeutic targets in idiopathic inflammatory myopathies", J Immunol Res, 2020, pp.9079083~ (2020)
- Zhang L, "Fatty acid binding protein 3 is associated with skeletal muscle strength in polymyositis and dermatomyositis", Int J Rheum Dis, 20, pp.252~260 (2017)
- Jaretzki A 3rd, "Myasthenia gravis : recommendations for clinical research standards. Task force of the medical scientific advisory board of the myasthenia gravis foundation of America", Neurology, 55, pp.16~23 (2000)
- Barohn RJ, "Reliability testing of the quantitative myasthenia gravis score", Ann N Y Acad Sci, 841, pp.769~772 (1998)
- Wolfe GI, "Myasthenia gravis activities of daily living profile", Neurology, 52, pp.1487~1489 (1999)
- Burns TM, "The MG Composite : a valid and reliable outcome measure for myasthenia gravis", Neurology, 74, pp.1434~1440 (2010)
- Klosowska K, "Fractalkine functions as a chemoattractant for osteoarthritis synovial fibroblasts and stimulates phosphorylation of mitogen-activated protein kinases and Akt", Clin Exp Immunol, 156, pp.312~319 (2009)
- Jones B, "Pathological role of fractalkine", CX3CL1in rheumatic diseases : a unique chemokine with multiple functions, 2011, pp.2, 82~
- Suzuki F, "Serum level of soluble CX3CL1", fractalkine is elevated in patients with polymyositis and dermatomyositis, which is correlated with disease activity, 2012, pp.14, R48~
- Matsunawa M, "Increased serum levels of soluble fractalkine(CX3CL1)correlate with disease activity in rheumatoid vasculitis", Arthritis Rheum, 54, pp.3408~3416 (2006)
- Lee JH, "Role of fractalkine in the pathogenesis of primary Sjögren syndrome : increased serum levels of fractalkine, its expression in labial salivary glands, and the association with clinical manifestations", J Rheumatol, 41, pp.2425~2438 (2014)
- Fahy OL, "Inhibition of cytokine-induced fractalkine production by bacterial invasion of human-dermal fibroblasts", Lab Invest, 83, pp.721~730 (2003)
- Fraticelli P, "Fractalkine(CX3CL1)as an amplification circuit of polarized Th1 responses", J Clin Invest, 107, pp.1173~1181 (2001)
- Uzawa A, "Serum cytokine and chemokine profiles in patients with myasthenia gravis", Clin Exp Immunol, 176, pp.232~237 (2014)
- Yilmaz V, "Differential cytokine changes in patients with myasthenia gravis with antibodies against AChR and MuSK", PLoS One, 10, pp.e0123546~ (2015)
- Uzawa A, "Roles of cytokines and T cells in the pathogenesis of myasthenia gravis", Clin Exp Immunol, 203, pp.366~374 (2021)
- Strömberg A, "CX3CL1--a macrophage chemoattractant induced by a single bout of exercise in human skeletal muscle", Am J Physiol Regul Integr Comp Physiol, 310, pp.R297~R304 (2016)
- Heuckeroth RO, "Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent gene encoding heart fatty acid binding protein", J Biol Chem, 262, pp.9709~9717 (1987)
- Kusudo T, "Fatty acid-binding protein 3 stimulates glucose uptake by facilitating AS160 phosphorylation in mouse muscle cells", Genes Cells, 16, pp.681~691 (2011)
- Lee SM, "FABP3-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging", Nat Commun, 11, pp.5661~ (2020)
- Furuhashi M, "Fatty acid-binding proteins : role in metabolic diseases and potential as drug targets", Nat Rev Drug Discov, 7, pp.489~503 (2008)
- Sorichter S, "Early assessment of exercise induced skeletal muscle injury using plasma fatty acid binding protein", Br J Sports Med, 32, pp.121~124 (1998)
- McDermott MM, "Skeletal muscle pathology in peripheral artery disease : a brief review", Arterioscler Thromb Vasc Biol, 40, pp.2577~2585 (2020)
- Syed MH, "Fatty acid binding protein 3 is associated with peripheral arterial disease", JVS Vasc Sci, 1, pp.168~175 (2020)
- Gupta L, "Serum fatty acid-binding protein 3 levels differentiate active from inactive myositis and correlate with response to therapy", Indian J Rheumatol, 15, pp.187~190 (2020)
- Plomp JJ, "A bioassay for neuromuscular junction-restricted complement activation by myasthenia gravis acetylcholine receptor antibodies", J Neurosci Methods, 373, pp.109551~ (2022)
- Luo YB, "Dermatomyositis, polymyositis and immunemediated necrotising myopathies", Biochim Biophys Acta, 1852, pp.622~632 (2015)
- Su S, "Clinical predictors of relapse in a cohort of steroid-treated patients with well-controlled myasthenia gravis", Front Neurol, 13, pp.816243~ (2022)
- Kim KH, "Anti-titin antibody is associated with more frequent hospitalization to manage thymomaassociated myasthenia gravis", Front Neurol, 13, pp.978997~ (2022)
- Narayanaswami P, "International consensus guidance for management of myasthenia gravis : 2020 update", Neurology, 96, pp.114~122 (2021)
- Sempowski GD, "Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy", J Immunol, 164, pp.2180~2187 (2000)
- Youm YH, "Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution", Proc Natl Acad Sci U S A, 113, pp.1026~1031 (2016)
- Drennan MB, "The thymic microenvironment differentially regulates development and trafficking of invariant NKT cell sublineages", J Immunol, 193, pp.5960~5972 (2014)
- Cufi P, "Implication of double-stranded RNA signaling in the etiology of autoimmune myasthenia gravis", Ann Neurol, 73, pp.281~293 (2013)
- Payet CA, "Myasthenia gravis : an acquired interferonopathy?", Cells, 11, pp.1218~ (2022)
- Lefeuvre CM, "Risk factors associated with myasthenia gravis in thymoma patients : the potential role of thymic germinal centers", J Autoimmun, 106, pp.102337~ (2020)
- Murillo-Saich JD, "Association of myostatin, a cytokine released by muscle, with inflammation in rheumatoid arthritis: a cross-sectional study", Medicine(Baltimore), 100, pp.e24186~ (2021)
- Ebert T, "Serum levels of the myokine irisin in relation to metabolic and renal function", Eur J Endocrinol, 170, pp.501~506 (2014)
- Singhal V, "Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates", PLoS One, 9, pp.e100218~ (2014)