Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2019

Open Access 01-12-2019 | Research article

The immune system in sporadic inclusion body myositis patients is not compromised by blood-flow restricted exercise training

Authors: Kasper Yde Jensen, Mikkel Jacobsen, Henrik Daa Schrøder, Per Aagaard, Jakob Lindberg Nielsen, Anders Nørkær Jørgensen, Eleanor Boyle, Rune Dueholm Bech, Sofie Rosmark, Louise Pyndt Diederichsen, Ulrik Frandsen

Published in: Arthritis Research & Therapy | Issue 1/2019

Login to get access

Abstract

Background

Sporadic inclusion body myositis (sIBM) is clinically characterised by progressive proximal and distal muscle weakness and impaired physical function while skeletal muscle tissue displays abnormal cellular infiltration of T cells, macrophages, and dendritic cells. Only limited knowledge exists about the effects of low-load blood flow restriction exercise in sIBM patients, and its effect on the immunological responses at the myocellular level remains unknown. The present study is the first to investigate the longitudinal effects of low-load blood flow restriction exercise on innate and adaptive immune markers in skeletal muscle from sIBM patients.

Methods

Twenty-two biopsy-validated sIBM patients were randomised into either 12 weeks of low-load blood flow restriction exercise (BFRE) or no exercise (CON). Five patients from the control group completed 12 weeks of BFRE immediately following participation in the 12-week control period leading to an intervention group of 16 patients. Muscle biopsies were obtained from either the m. tibialis anterior or the m. vastus lateralis for evaluation of CD3-, CD8-, CD68-, CD206-, CD244- and FOXP3-positive cells by three-colour immunofluorescence microscopy and Visiopharm-based image analysis quantification. A linear mixed model was used for the statistical analysis.

Results

Myocellular infiltration of CD3−/CD8+ expressing natural killer cells increased following BFRE (P < 0.05) with no changes in CON. No changes were observed for CD3+/CD8− or CD3+/CD8+ T cells in BFRE or CON. CD3+/CD244+ T cells decreased in CON, while no changes were observed in BFRE. Pronounced infiltration of M1 pro-inflammatory (CD68+/CD206−) and M2 anti-inflammatory (CD68+/CD206+) macrophages were observed at baseline; however, no longitudinal changes in macrophage content were observed for both groups.

Conclusions

Low-load blood flow restriction exercise elicited an upregulation in CD3−/CD8+ expressing natural killer cell content, which suggests that 12 weeks of BFRE training evokes an amplified immune response in sIBM muscle. However, the observation of no changes in macrophage or T cell infiltration in the BFRE-trained patients indicates that patients with sIBM may engage in this type of exercise with no risk of intensified inflammatory activity.
Literature
1.
Greenberg SA. Inclusion body myositis: clinical features and pathogenesis. Nat Rev Rheumatol. 2019;15(5):257–72.PubMedCrossRef
2.
Yunis EJ, Samaha FJ. Inclusion body myositis. Lab Invest. 1971;25(3):240–8.PubMed
3.
Griggs RC, Askanas V, DiMauro S, Engel A, Karpati G, Mendell JR, et al. Inclusion body myositis and myopathies. Ann Neurol. 1995;38(5):705–13.PubMedCrossRef
4.
Karpati G, O'Ferrall EK. Sporadic inclusion body myositis: pathogenic considerations. Ann Neurol. 2009;65(1):7–11.PubMedCrossRef
5.
Askanas V, Engel WK, Nogalska A. Pathogenic considerations in sporadic inclusion-body myositis, a degenerative muscle disease associated with aging and abnormalities of myoproteostasis. J Neuropathol Exp Neurol. 2012;71(8):680–93.PubMedCrossRef
6.
Cox FM, Titulaer MJ, Sont JK, Wintzen AR, Verschuuren JJ, Badrising UA. A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities. Brain. 2011;134(Pt 11):3167–75.PubMedCrossRef
7.
Hogrel JY, Allenbach Y, Canal A, Leroux G, Ollivier G, Mariampillai K, et al. Four-year longitudinal study of clinical and functional endpoints in sporadic inclusion body myositis: implications for therapeutic trials. Neuromuscular Disord. 2014;24(7):604–10.CrossRef
8.
Skelton DA, Greig CA, Davies JM, Young A. Strength, power and related functional ability of healthy people aged 65-89 years. Age Ageing. 1994;23(5):371–7.PubMedCrossRef
9.
Pearson SJ, Young A, Macaluso A, Devito G, Nimmo MA, Cobbold M, et al. Muscle function in elite master weightlifters. Med Sci Sports Exerc. 2002;34(7):1199–206.PubMedCrossRef
10.
Askanas V, Engel WK. Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer’s and Parkinson’s disease brains. Acta Neuropathol. 2008;116(6):583–95.PubMedPubMedCentralCrossRef
11.
Lundberg IE, Nader GA. Molecular effects of exercise in patients with inflammatory rheumatic disease. Nat Clin Pract Rheumatol. 2008;4(11):597–604.PubMedCrossRef
12.
Nader GA, Lundberg IE. Exercise as an anti-inflammatory intervention to combat inflammatory diseases of muscle. Curr Opin Rheumatol. 2009;21(6):599–603.PubMedCrossRef
13.
Alexanderson H. Exercise in myositis. Curr Treat Options Rheumatol. 2018;4(4):289–98.CrossRef
14.
Benatti FB, Pedersen BK. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat Rev Rheumatol. 2015;11(2):86–97.PubMedCrossRef
15.
Dorneles GP, Colato AS, Galvao SL, Ramis TR, Ribeiro JL, Romao PR, et al. Acute response of peripheral CCr5 chemoreceptor and NK cells in individuals submitted to a single session of low-intensity strength exercise with blood flow restriction. Clin Physiol Funct Imaging. 2016;36(4):311–7.PubMedCrossRef
16.
Nielsen JL, Aagaard P, Prokhorova TA, Nygaard T, Bech RD, Suetta C, et al. Blood flow restricted training leads to myocellular macrophage infiltration and upregulation of heat shock proteins, but no apparent muscle damage. J Physiol. 2017;595(14):4857–73.PubMedPubMedCentralCrossRef
17.
Hughes L, Paton B, Rosenblatt B, Gissane C, Patterson SD. Blood flow restriction training in clinical musculoskeletal rehabilitation: a systematic review and meta-analysis. Br J Sports Med. 2017;51(13):1003–11.PubMedCrossRef
18.
Gualano B, Neves M Jr, Lima FR, Pinto AL, Laurentino G, Borges C, et al. Resistance training with vascular occlusion in inclusion body myositis: a case study. Med Sci Sports Exerc. 2010;42(2):250–4.PubMedCrossRef
19.
Jorgensen AN, Aagaard P, Nielsen JL, Frandsen U, Diederichsen LP. Effects of blood-flow-restricted resistance training on muscle function in a 74-year-old male with sporadic inclusion body myositis: a case report. Clin Physiol Funct Imaging. 2016;36(6):504–9.PubMedCrossRef
20.
Mattar MA, Gualano B, Perandini LA, Shinjo SK, Lima FR, Sa-Pinto AL, et al. Safety and possible effects of low-intensity resistance training associated with partial blood flow restriction in polymyositis and dermatomyositis. Arthritis Re Ther. 2014;16(5):473.CrossRef
21.
Jorgensen AN, Aagaard P, Frandsen U, Boyle E, Diederichsen LP. Blood-flow restricted resistance training in patients with sporadic inclusion body myositis: a randomized controlled trial. Scand J Rheumatol. 2018;47(5):400–9.PubMedCrossRef
22.
Pandya JM, Fasth AE, Zong M, Arnardottir S, Dani L, Lindroos E, et al. Expanded T cell receptor Vbeta-restricted T cells from patients with sporadic inclusion body myositis are proinflammatory and cytotoxic CD28null T cells. Arthritis Rheum. 2010;62(11):3457–66.PubMedCrossRef
23.
Pandya JM, Loell I, Hossain MS, Zong M, Alexanderson H, Raghavan S, et al. Effects of conventional immunosuppressive treatment on CD244+ (CD28null) and FOXP3+ T cells in the inflamed muscle of patients with polymyositis and dermatomyositis. Arthritis Res Ther. 2016;18:80.PubMedPubMedCentralCrossRef
24.
Pandya JM, Venalis P, Al-Khalili L, Shahadat Hossain M, Stache V, Lundberg IE, et al. CD4+ and CD8+ CD28(null) T cells are cytotoxic to autologous muscle cells in patients with polymyositis. Arthritis Rheumatol. 2016;68(8):2016–26.PubMedCrossRef
25.
26.
27.
Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133(5):775–87.PubMedCrossRef
28.
Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010;10(7):490–500.PubMedCrossRef
29.
Waschbisch A, Schwab N, Ruck T, Stenner MP, Wiendl H. FOXP3+ T regulatory cells in idiopathic inflammatory myopathies. J Neuroimmunol. 2010;225(1–2):137–42.PubMedCrossRef
30.
Castiglioni A, Corna G, Rigamonti E, Basso V, Vezzoli M, Monno A, et al. FOXP3+ T cells recruited to sites of sterile skeletal muscle injury regulate the fate of satellite cells and guide effective tissue regeneration. PLoS One. 2015;10(6):e0128094.PubMedPubMedCentralCrossRef
31.
32.
33.
Allenbach Y, Chaara W, Rosenzwajg M, Six A, Prevel N, Mingozzi F, et al. Th1 response and systemic treg deficiency in inclusion body myositis. PLoS One. 2014;9(3):e88788.PubMedPubMedCentralCrossRef
34.
Tidball JG, Wehling-Henricks M. Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J Physiol. 2007;578(Pt 1):327–36.PubMedCrossRef
35.
Massimino ML, Rapizzi E, Cantini M, Libera LD, Mazzoleni F, Arslan P, et al. ED2+ macrophages increase selectively myoblast proliferation in muscle cultures. Biochem Biophys Res Commun. 1997;235(3):754–9.PubMedCrossRef
36.
Gleeson M, Bishop NC. The T cell and NK cell immune response to exercise. Ann Transplantation. 2005;10(4):43–8.
37.
Bigley AB, Simpson RJ. NK cells and exercise: implications for cancer immunotherapy and survivorship. Discov Med. 2015;19(107):433–45.PubMed
38.
Jorgensen AN, Aagaard P, Nielsen JL, Christiansen M, Hvid LG, Frandsen U, et al. Physical function and muscle strength in sporadic inclusion body myositis. Muscle Nerve. 2017;56(6):E50–e8.PubMedCrossRef
39.
Nielsen JL, Aagaard P, Bech RD, Nygaard T, Hvid LG, Wernbom M, et al. Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance training with blood flow restriction. J Physiol. 2012;590(17):4351–61.PubMedPubMedCentralCrossRef
40.
Nader GA, Dastmalchi M, Alexanderson H, Grundtman C, Gernapudi R, Esbjornsson M, et al. A longitudinal, integrated, clinical, histological and mRNA profiling study of resistance exercise in myositis. Mol Med. 2010;16(11–12):455–64.PubMedPubMedCentralCrossRef
41.
Munters LA, Loell I, Ossipova E, Raouf J, Dastmalchi M, Lindroos E, et al. Endurance exercise improves molecular pathways of aerobic metabolism in patients with myositis. Arthritis Rheumatol. 2016;68(7):1738–50.PubMedCrossRef
42.
Fasth AE, Dastmalchi M, Rahbar A, Salomonsson S, Pandya JM, Lindroos E, et al. T cell infiltrates in the muscles of patients with dermatomyositis and polymyositis are dominated by CD28null T cells. J Immunol. 2009;183(7):4792–9.PubMedCrossRef
43.
Loell I, Pandya J, Raghvan S, Zong M, Malmström V, Lundberg IE. Persisting CD28<sup>null</sup> T cells, but not regulatory T cells, in muscle tissue of myositis patients after immunosuppressive therapy. Ann Rheumatic Dis. 2012;71(Suppl 1):A44-A.
44.
Pandya J, Venalis P, Stache V, Al-Khalili L, Malmström V, Lundberg I, et al. CD28<sup>null</sup> T cells from myositis patients are cytotoxic to autologous muscle cells in vitro. Ann Rheum Dis. 2012;71(Suppl 1):A44–A5.CrossRef
45.
Vallejo AN. CD28 extinction in human T cells: altered functions and the program of T-cell senescence. Immunol Rev. 2005;205:158–69.PubMedCrossRef
46.
Fagnoni FF, Vescovini R, Mazzola M, Bologna G, Nigro E, Lavagetto G, et al. Expansion of cytotoxic CD8+ CD28- T cells in healthy ageing people, including centenarians. Immunology. 1996;88(4):501–7.PubMedPubMedCentralCrossRef
47.
Effros RB, Boucher N, Porter V, Zhu X, Spaulding C, Walford RL, et al. Decline in CD28+ T cells in centenarians and in long-term T cell cultures: a possible cause for both in vivo and in vitro immunosenescence. Exp Gerontol. 1994;29(6):601–9.PubMedCrossRef
48.
49.
Wilson LD, Zaldivar FP, Schwindt CD, Wang-Rodriguez J, Cooper DM. Circulating T-regulatory cells, exercise and the elite adolescent swimmer. Pediatr Exerc Sci. 2009;21(3):305–17.PubMedPubMedCentralCrossRef
50.
Kruger K, Alack K, Ringseis R, Mink L, Pfeifer E, Schinle M, et al. Apoptosis of T-cell subsets after acute high-intensity interval exercise. Med Sci Sports Exerc. 2016;48(10):2021–9.PubMedCrossRef
51.
Young NA, Sharma R, Friedman AK, Kaffenberger BH, Bolon B, Jarjour WN. Aberrant muscle antigen exposure in mice is sufficient to cause myositis in a Treg cell-deficient milieu. Arthritis Rheum. 2013;65(12):3259–70.PubMedPubMedCentralCrossRef
52.
Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol. 2005;98(4):1154–62.CrossRefPubMed
53.
Schiaffino S, Pereira MG, Ciciliot S, Rovere-Querini P. Regulatory T cells and skeletal muscle regeneration. FEBS J. 2017;284(4):517–24.PubMedCrossRef
54.
Weavers H, Evans IR, Martin P, Wood W. Corpse engulfment generates a molecular memory that primes the macrophage inflammatory response. Cell. 2016;165(7):1658–71.PubMedPubMedCentralCrossRef
55.
Moretta L, Bottino C, Pende D, Vitale M, Mingari MC, Moretta A. Human natural killer cells: molecular mechanisms controlling NK cell activation and tumor cell lysis. Immunol Lett. 2005;100(1):7–13.PubMedCrossRef
56.
Shepard RJ, Shek PN. Impact of physical activity and sport on the immune system. Rev Environ Health. 1996;11(3):133–47.PubMed
57.
Nieman DC, Henson DA, Gusewitch G, Warren BJ, Dotson RC, Butterworth DE, et al. Physical activity and immune function in elderly women. Med Sci Sports Exerc. 1993;25(7):823–31.PubMedCrossRef
58.
De Bleecker JL, De Paepe B, Aronica E, de Visser M, Amato A, Aronica E, et al. 205th ENMC International Workshop: pathology diagnosis of idiopathic inflammatory myopathies part II 28-30 March 2014, Naarden, The Netherlands. Neuromuscular Disord. 2015;25(3):268–72.CrossRef
Metadata
Title
The immune system in sporadic inclusion body myositis patients is not compromised by blood-flow restricted exercise training
Authors
Kasper Yde Jensen
Mikkel Jacobsen
Henrik Daa Schrøder
Per Aagaard
Jakob Lindberg Nielsen
Anders Nørkær Jørgensen
Eleanor Boyle
Rune Dueholm Bech
Sofie Rosmark
Louise Pyndt Diederichsen
Ulrik Frandsen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2019
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-019-2036-2

Other articles of this Issue 1/2019

Arthritis Research & Therapy 1/2019 Go to the issue

Review

The burden of metabolic syndrome on osteoarthritic joints

Research article

Interferon-α exacerbates neuropsychiatric phenotypes in lupus-prone mice

Research article

Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis

Correction

Correction to: The association between sonographic enthesitis and radiographic damage in psoriatic arthritis

Research article

A novel function of artesunate on inhibiting migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients

Research article

Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits