Inclusion body myositis: clinical features and pathogenesis.
Journal
Nature reviews. Rheumatology
ISSN: 1759-4804
Titre abrégé: Nat Rev Rheumatol
Pays: United States
ID NLM: 101500080
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
pubmed:
7
3
2019
medline:
20
2
2020
entrez:
7
3
2019
Statut:
ppublish
Résumé
Inclusion body myositis (IBM) is often viewed as an enigmatic disease with uncertain pathogenic mechanisms and confusion around diagnosis, classification and prospects for treatment. Its clinical features (finger flexor and quadriceps weakness) and pathological features (invasion of myofibres by cytotoxic T cells) are unique among muscle diseases. Although IBM T cell autoimmunity has long been recognized, enormous attention has been focused for decades on several biomarkers of myofibre protein aggregates, which are present in <1% of myofibres in patients with IBM. This focus has given rise, together with the relative treatment refractoriness of IBM, to a competing view that IBM is not an autoimmune disease. Findings from the past decade that implicate autoimmunity in IBM include the identification of a circulating autoantibody (anti-cN1A); the absence of any statistically significant genetic risk factor other than the common autoimmune disease 8.1 MHC haplotype in whole-genome sequencing studies; the presence of a marked cytotoxic T cell signature in gene expression studies; and the identification in muscle and blood of large populations of clonal highly differentiated cytotoxic CD8
Identifiants
pubmed: 30837708
doi: 10.1038/s41584-019-0186-x
pii: 10.1038/s41584-019-0186-x
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
257-272Références
Unverricht, H. Polymyositis acuta progressiva. Z. Klin. Med. 12, 533–549 (1887).
Bohan, A. History and classification of polymyositis and dermatomyositis. Clin. Dermatol. 6, 3–8 (1988).
doi: 10.1016/0738-081X(88)90044-2
Uverricht, H. Dermatomyositis acuta. Dtsch. Med. Wochenschr. 17, 41–44 (1891).
doi: 10.1055/s-0029-1206170
Levine, T. D. History of dermatomyositis. Arch. Neurol. 60, 780–782 (2003).
doi: 10.1001/archneur.60.5.780
Carpenter, S., Karpati, G., Heller, I. & Eisen, A. Inclusion body myositis: a distinct variety of idiopathic inflammatory myopathy. Neurology 28, 8–17 (1978).
doi: 10.1212/WNL.28.1.8
Emslie-Smith, A. M. & Engel, A. G. Necrotizing myopathy with pipestem capillaries, microvascular deposition of the complement membrane attack complex (MAC), and minimal cellular infiltration. Neurology 41, 936–939 (1991).
doi: 10.1212/WNL.41.6.936
van der Meulen, M. F. et al. Polymyositis: an overdiagnosed entity. Neurology 61, 316–321 (2003).
doi: 10.1212/WNL.61.3.316
Hoogendijk, J. E. et al. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10-12 October 2003, Naarden, The Netherlands. Neuromuscul. Disord. 14, 337–345 (2004).
doi: 10.1016/j.nmd.2004.02.006
van de Vlekkert, J., Hoogendijk, J. E. & de Visser, M. Myositis with endomysial cell invasion indicates inclusion body myositis even if other criteria are not fulfilled. Neuromuscul. Disord. 25, 451–456 (2015).
doi: 10.1016/j.nmd.2015.02.014
Dalakas, M. C. Inflammatory muscle diseases. N. Engl. J. Med. 372, 1734–1747 (2015).
doi: 10.1056/NEJMra1402225
Wolstencroft, P. W. & Fiorentino, D. F. Dermatomyositis clinical and pathological phenotypes associated with myositis-specific autoantibodies. Curr. Rheumatol. Rep. 20, 28 (2018).
doi: 10.1007/s11926-018-0733-5
Schmidt, J. & Dalakas, M. C. Inclusion body myositis: from immunopathology and degenerative mechanisms to treatment perspectives. Expert Rev. Clin. Immunol. 9, 1125–1133 (2013).
doi: 10.1586/1744666X.2013.842467
Machado, P. M. et al. Ongoing developments in sporadic inclusion body myositis. Curr. Rheumatol. Rep. 16, 477 (2014).
doi: 10.1007/s11926-014-0477-9
pubmed: 4233319
pmcid: 4233319
Dimachkie, M. M. & Barohn, R. J. Inclusion body myositis. Neurol. Clin. 32, 629–646 (2014).
doi: 10.1016/j.ncl.2014.04.001
pubmed: 4115580
pmcid: 4115580
Mastaglia, F. L. & Needham, M. Inclusion body myositis: a review of clinical and genetic aspects, diagnostic criteria and therapeutic approaches. J. Clin. Neurosci. 22, 6–13 (2015).
doi: 10.1016/j.jocn.2014.09.012
Greenberg, S. A. Inclusion body myositis. Continuum 22, 1871–1888 (2016).
pubmed: 27922498
Gallay, L. & Petiot, P. Sporadic inclusion-body myositis: recent advances and the state of the art in 2016. Rev. Neurol. 172, 581–586 (2016).
doi: 10.1016/j.neurol.2016.07.016
Needham, M. & Mastaglia, F. L. Sporadic inclusion body myositis: a review of recent clinical advances and current approaches to diagnosis and treatment. Clin. Neurophysiol. 127, 1764–1773 (2016).
doi: 10.1016/j.clinph.2015.12.011
Schmidt, K. & Schmidt, J. Inclusion body myositis: advancements in diagnosis, pathomechanisms, and treatment. Curr. Opin. Rheumatol. 29, 632–638 (2017).
pubmed: 28832349
Benveniste, O. et al. Amyloid deposits and inflammatory infiltrates in sporadic inclusion body myositis: the inflammatory egg comes before the degenerative chicken. Acta Neuropathol. 129, 611–624 (2015).
doi: 10.1007/s00401-015-1384-5
pubmed: 4405277
pmcid: 4405277
Keller, C. W., Schmidt, J. & Lunemann, J. D. Immune and myodegenerative pathomechanisms in inclusion body myositis. Ann. Clin. Transl Neurol. 4, 422–445 (2017).
doi: 10.1002/acn3.419
pubmed: 5454400
pmcid: 5454400
Chou, S. M. Myxovirus-like structures in a case of human chronic polymyositis. Science 158, 1453–1455 (1967).
doi: 10.1126/science.158.3807.1453
Nishino, H., Engel, A. G. & Rima, B. K. Inclusion body myositis: the mumps virus hypothesis. Ann. Neurol. 25, 260–264 (1989).
doi: 10.1002/ana.410250309
Kallajoki, M. et al. Inclusion body myositis and paramyxoviruses. Hum. Pathol. 22, 29–32 (1991).
doi: 10.1016/0046-8177(91)90057-V
Fox, S. A., Ward, B. K., Robbins, P. D., Mastaglia, F. L. & Swanson, N. R. Inclusion body myositis: investigation of the mumps virus hypothesis by polymerase chain reaction. Muscle Nerve 19, 23–28 (1996).
doi: 10.1002/(SICI)1097-4598(199601)19:1<23::AID-MUS4>3.0.CO;2-A
Uruha, A. et al. Hepatitis C virus infection in inclusion body myositis: a case-control study. Neurology 86, 211–217 (2016).
doi: 10.1212/WNL.0000000000002291
Yunis, E. J. & Samaha, F. J. Inclusion body myositis. Lab. Invest. 25, 240–248 (1971).
pubmed: 5095321
Danon, M. J., Reyes, M. G., Perurena, O. H., Masdeu, J. C. & Manaligod, J. R. Inclusion body myositis. A corticosteroid-resistant idiopathic inflammatory myopathy. Arch. Neurol. 39, 760–764 (1982).
doi: 10.1001/archneur.1982.00510240022006
Eisen, A., Berry, K. & Gibson, G. Inclusion body myositis (IBM): myopathy or neuropathy? Neurology 33, 1109–1114 (1983).
doi: 10.1212/WNL.33.9.1109
Ringel, S. P., Kenny, C. E., Neville, H. E., Giorno, R. & Carry, M. R. Spectrum of inclusion body myositis. Arch. Neurol. 44, 1154–1157 (1987).
doi: 10.1001/archneur.1987.00520230042011
Calabrese, L. H., Mitsumoto, H. & Chou, S. M. Inclusion body myositis presenting as treatment-resistant polymyositis. Arthritis Rheum. 30, 397–403 (1987).
doi: 10.1002/art.1780300406
Lotz, B. P., Engel, A. G., Nishino, H., Stevens, J. C. & Litchy, W. J. Inclusion body myositis. Observations in 40 patients. Brain 112, 727–747 (1989).
doi: 10.1093/brain/112.3.727
Sayers, M. E., Chou, S. M. & Calabrese, L. H. Inclusion body myositis: analysis of 32 cases. J. Rheumatol. 19, 1385–1389 (1992).
pubmed: 1331441
Lindberg, C., Persson, L. I., Bjorkander, J. & Oldfors, A. Inclusion body myositis: clinical, morphological, physiological and laboratory findings in 18 cases. Acta Neurol. Scand. 89, 123–131 (1994).
doi: 10.1111/j.1600-0404.1994.tb01647.x
Amato, A. A. et al. Inclusion body myositis: clinical and pathological boundaries. Ann. Neurol. 40, 581–586 (1996).
doi: 10.1002/ana.410400407
Felice, K. J., Relva, G. M. & Conway, S. R. Further observations on forearm flexor weakness in inclusion body myositis. Muscle Nerve 21, 659–661 (1998).
doi: 10.1002/(SICI)1097-4598(199805)21:5<659::AID-MUS17>3.0.CO;2-Q
Phillips, B. A. et al. Patterns of muscle involvement in inclusion body myositis: clinical and magnetic resonance imaging study. Muscle Nerve 24, 1526–1534 (2001).
doi: 10.1002/mus.1178
Badrising, U. A. et al. Inclusion body myositis. Clinical features and clinical course of the disease in 64 patients. J. Neurol. 252, 1448–1454 (2005).
doi: 10.1007/s00415-005-0884-y
Benveniste, O. et al. Long-term observational study of sporadic inclusion body myositis. Brain 134, 3176–3184 (2011).
doi: 10.1093/brain/awr213
Price, M. A. et al. Mortality and causes of death in patients with sporadic inclusion body myositis: survey study based on the clinical experience of specialists in Australia, Europe and the USA. J. Neuromuscul. Dis. 3, 67–75 (2016).
doi: 10.3233/JND-150138
pubmed: 5271419
pmcid: 5271419
Felice, K. J. & North, W. A. Inclusion body myositis in Connecticut: observations in 35 patients during an 8-year period. Medicine 80, 320–327 (2001).
doi: 10.1097/00005792-200109000-00006
Needham, M. et al. Sporadic inclusion body myositis: phenotypic variability and influence of HLA-DR3 in a cohort of 57 Australian cases. J. Neurol. Neurosurg. Psychiatry 79, 1056–1060 (2008).
doi: 10.1136/jnnp.2007.138891
Cox, F. M. et al. A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities. Brain 134, 3167–3175 (2011).
doi: 10.1093/brain/awr217
Cortese, A. et al. Longitudinal observational study of sporadic inclusion body myositis: implications for clinical trials. Neuromuscul. Disord. 23, 404–412 (2013).
doi: 10.1016/j.nmd.2013.02.010
Hogrel, J. Y. et al. Four-year longitudinal study of clinical and functional endpoints in sporadic inclusion body myositis: implications for therapeutic trials. Neuromuscul. Disord. 24, 604–610 (2014).
doi: 10.1016/j.nmd.2014.04.009
Alfano, L. N. et al. Modeling functional decline over time in sporadic inclusion body myositis. Muscle Nerve 55, 526–531 (2016).
doi: 10.1002/mus.25373
Rose, M. R. et al. A prospective natural history study of inclusion body myositis: implications for clinical trials. Neurology 57, 548–550 (2001).
doi: 10.1212/WNL.57.3.548
Arahata, K. & Engel, A. G. Monoclonal antibody analysis of mononuclear cells in myopathies. I: Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells. Ann. Neurol. 16, 193–208 (1984).
doi: 10.1002/ana.410160206
Engel, A. G. & Arahata, K. Monoclonal antibody analysis of mononuclear cells in myopathies. II: Phenotypes of autoinvasive cells in polymyositis and inclusion body myositis. Ann. Neurol. 16, 209–215 (1984).
doi: 10.1002/ana.410160207
Arahata, K. & Engel, A. G. Monoclonal antibody analysis of mononuclear cells in myopathies. III: Immunoelectron microscopy aspects of cell-mediated muscle fiber injury. Ann. Neurol. 19, 112–125 (1986).
doi: 10.1002/ana.410190203
Arahata, K. & Engel, A. G. Monoclonal antibody analysis of mononuclear cells in myopathies. IV: Cell-mediated cytotoxicity and muscle fiber necrosis. Ann. Neurol. 23, 168–173 (1988).
doi: 10.1002/ana.410230210
O’Hanlon, T. P., Dalakas, M. C., Plotz, P. H. & Miller, F. W. The αβT cell receptor repertoire in inclusion body myositis: diverse patterns of gene expression by muscle-infiltrating lymphocytes. J. Autoimmun. 7, 321–333 (1994).
doi: 10.1006/jaut.1994.1023
Lindberg, C., Oldfors, A. & Tarkowski, A. Restricted use of T cell receptor V genes in endomysial infiltrates of patients with inflammatory myopathies. Eur. J. Immunol. 24, 2659–2663 (1994).
doi: 10.1002/eji.1830241114
Lindberg, C., Oldfors, A. & Tarkowski, A. Local T cell proliferation and differentiation in inflammatory myopathies. Scand. J. Immunol. 41, 421–426 (1995).
doi: 10.1111/j.1365-3083.1995.tb03587.x
Fyhr, I. M., Moslemi, A. R., Tarkowski, A., Lindberg, C. & Oldfors, A. Limited T cell receptor V gene usage in inclusion body myositis. Scand. J. Immunol. 43, 109–114 (1996).
doi: 10.1046/j.1365-3083.1996.d01-10.x
Fyhr, I. M. et al. Oligoclonal expansion of muscle infiltrating T cells in inclusion body myositis. J. Neuroimmunol. 79, 185–189 (1997).
doi: 10.1016/S0165-5728(97)00122-7
Bender, A., Behrens, L., Engel, A. G. & Hohlfeld, R. T cell heterogeneity in muscle lesions of inclusion body myositis. J. Neuroimmunol. 84, 86–91 (1998).
doi: 10.1016/S0165-5728(97)00246-4
Amemiya, K., Granger, R. P. & Dalakas, M. C. Clonal restriction of T cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time. Studies in repeated muscle biopsies. Brain 123, 2030–2039 (2000).
pubmed: 11004120
Muntzing, K., Lindberg, C., Moslemi, A. R. & Oldfors, A. Inclusion body myositis: clonal expansions of muscle-infiltrating T cells persist over time. Scand. J. Immunol. 58, 195–200 (2003).
doi: 10.1046/j.1365-3083.2003.01251.x
Dimitri, D. et al. Shared blood and muscle CD8
doi: 10.1093/brain/awl020
Salajegheh, M. et al. T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis. Neurology 69, 1672–1679 (2007).
doi: 10.1212/01.wnl.0000265398.77681.09
Pandya, J. M. et al. Expanded T cell receptor Vβ-restricted T cells from patients with sporadic inclusion body myositis are proinflammatory and cytotoxic CD28
doi: 10.1002/art.27665
Allenbach, Y. et al. Th1 response and systemic treg deficiency in inclusion body myositis. PLOS ONE 9, e88788 (2014).
doi: 10.1371/journal.pone.0088788
pubmed: 3942319
pmcid: 3942319
Greenberg, S. A., Pinkus, J. L., Amato, A. A., Kristensen, T. & Dorfman, D. M. Association of inclusion body myositis with T cell large granular lymphocytic leukaemia. Brain 139, 1348–1360 (2016).
doi: 10.1093/brain/aww024
Hohlfeld, R. & Schulze-Koops, H. Cytotoxic T cells go awry in inclusion body myositis. Brain 139, 1312–1314 (2016).
doi: 10.1093/brain/aww053
Lindberg, C., Trysberg, E., Tarkowski, A. & Oldfors, A. Anti-T-lymphocyte globulin treatment in inclusion body myositis: a randomized pilot study. Neurology 61, 260–262 (2003).
doi: 10.1212/01.WNL.0000071852.27182.C7
Dalakas, M. C. et al. Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain 132, 1536–1544 (2009).
doi: 10.1093/brain/awp104
pubmed: 2685923
pmcid: 2685923
Hogrel, J. Y. et al. Rapamycin vs. placebo for the treatment of inclusion body myositis: improvement of the 6 min walking distance, a functional scale, the FVC and muscle quantitative MRI. Arthritis Rheumatol. 69, 5L (2017).
doi: 10.1002/acr.22992
Targoff, I. N. Autoantibodies and their significance in myositis. Curr. Rheumatol. Rep. 10, 333–340 (2008).
doi: 10.1007/s11926-008-0053-2
Nishikai, M. & Reichlin, M. Heterogeneity of precipitating antibodies in polymyositis and dermatomyositis. Characterization of the Jo-1 antibody system. Arthritis Rheum. 23, 881–888 (1980).
doi: 10.1002/art.1780230802
Reichlin, M. & Mattioli, M. Description of a serological reaction characteristic of polymyositis. Clin. Immunol. Immunopathol. 5, 12–20 (1976).
doi: 10.1016/0090-1229(76)90145-8
McHugh, N. J. & Tansley, S. L. Autoantibodies in myositis. Nat. Rev. Rheumatol. 14, 290–302 (2018).
doi: 10.1038/nrrheum.2018.56
Greenberg, S. A. et al. Molecular profiles of inflammatory myopathies. Neurology 59, 1170–1182 (2002).
doi: 10.1212/WNL.59.8.1170
Greenberg, S. A. et al. Plasma cells in muscle in inclusion body myositis and polymyositis. Neurology 65, 1782–1787 (2005).
doi: 10.1212/01.wnl.0000187124.92826.20
Bradshaw, E. M. et al. A local antigen-driven humoral response is present in the inflammatory myopathies. J. Immunol. 178, 547–556 (2007).
doi: 10.4049/jimmunol.178.1.547
Salajegheh, M. et al. Permissive environment for B cell maturation in myositis muscle in the absence of B cell follicles. Muscle Nerve 42, 576–583 (2010).
doi: 10.1002/mus.21739
Ray, A. et al. Autoantibodies produced at the site of tissue damage provide evidence of humoral autoimmunity in inclusion body myositis. PLOS ONE 7, e46709 (2012).
doi: 10.1371/journal.pone.0046709
pubmed: 3465259
pmcid: 3465259
Salajegheh, M., Lam, T. & Greenberg, S. A. Autoantibodies against a 43kDa muscle protein in inclusion body myositis. PLOS ONE 6, e20266 (2011).
doi: 10.1371/journal.pone.0020266
pubmed: 3100335
pmcid: 3100335
Larman, H. B. et al. Cytosolic 5′-nucleotidase 1A autoimmunity in sporadic inclusion body myositis. Ann. Neurol. 73, 408–418 (2013).
doi: 10.1002/ana.23840
Pluk, H. et al. Autoantibodies to cytosolic 5′-nucleotidase IA in inclusion body myositis. Ann. Neurol. 73, 397–407 (2013).
doi: 10.1002/ana.23822
Mendell, J. R., Sahenk, Z., Gales, T. & Paul, L. Amyloid filaments in inclusion body myositis. Novel findings provide insight into nature of filaments. Arch. Neurol. 48, 1229–1234 (1991).
doi: 10.1001/archneur.1991.00530240033013
Oldfors, A., Larsson, N. G., Lindberg, C. & Holme, E. Mitochondrial DNA deletions in inclusion body myositis. Brain 116, 325–336 (1993).
doi: 10.1093/brain/116.2.325
Schmidt, J. et al. Interrelation of inflammation and APP in sIBM: IL-1β induces accumulation of β-amyloid in skeletal muscle. Brain 131, 1228–1240 (2008).
doi: 10.1093/brain/awn053
pubmed: 2367696
pmcid: 2367696
Freret, M. et al. Overexpression of MHC class I in muscle of lymphocyte-deficient mice causes a severe myopathy with induction of the unfolded protein response. Am. J. Pathol. 183, 893–904 (2013).
doi: 10.1016/j.ajpath.2013.06.003
Rygiel, K. A. et al. Mitochondrial and inflammatory changes in sporadic inclusion body myositis. Neuropathol. Appl. Neurobiol. 41, 288–303 (2015).
doi: 10.1111/nan.12149
pubmed: 4833191
pmcid: 4833191
Garlepp, M. J., Laing, B., Zilko, P. J., Ollier, W. & Mastaglia, F. L. HLA associations with inclusion body myositis. Clin. Exp. Immunol. 98, 40–45 (1994).
doi: 10.1111/j.1365-2249.1994.tb06604.x
pubmed: 1534165
pmcid: 1534165
Koffman, B. M., Sivakumar, K., Simonis, T., Stroncek, D. & Dalakas, M. C. HLA allele distribution distinguishes sporadic inclusion body myositis from hereditary inclusion body myopathies. J. Neuroimmunol. 84, 139–142 (1998).
doi: 10.1016/S0165-5728(97)00245-2
Lampe, J. B. et al. Analysis of HLA class I and II alleles in sporadic inclusion-body myositis. J. Neurol. 250, 1313–1317 (2003).
doi: 10.1007/s00415-003-0204-3
Price, P. et al. Two major histocompatibility complex haplotypes influence susceptibility to sporadic inclusion body myositis: critical evaluation of an association with HLA-DR3. Tissue Antigens 64, 575–580 (2004).
doi: 10.1111/j.1399-0039.2004.00310.x
Scott, A. P. et al. Sporadic inclusion body myositis in Japanese is associated with the MHC ancestral haplotype 52.1. Neuromuscul. Disord. 16, 311–315 (2006).
doi: 10.1016/j.nmd.2006.02.002
Rojana-udomsart, A. et al. The association of sporadic inclusion body myositis and Sjögren’s syndrome in carriers of HLA-DR3 and the 8.1 MHC ancestral haplotype. Clin. Neurol. Neurosurg. 113, 559–563 (2011).
doi: 10.1016/j.clineuro.2011.03.016
Rojana-udomsart, A. et al. High-resolution HLA-DRB1 genotyping in an Australian inclusion body myositis (s-IBM) cohort: an analysis of disease-associated alleles and diplotypes. J. Neuroimmunol. 250, 77–82 (2012).
doi: 10.1016/j.jneuroim.2012.05.003
Rojana-udomsart, A. et al. Analysis of HLA-DRB3 alleles and supertypical genotypes in the MHC class II region in sporadic inclusion body myositis. J. Neuroimmunol. 254, 174–177 (2013).
doi: 10.1016/j.jneuroim.2012.09.003
Rothwell, S. et al. Immune-array analysis in sporadic inclusion body myositis reveals HLA-DRB1 amino acid heterogeneity across the myositis spectrum. Arthritis Rheumatol. 69, 1090–1099 (2017).
doi: 10.1002/art.40045
pubmed: 5516174
pmcid: 5516174
Dalakas, M. C. et al. Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. Neurology 48, 712–716 (1997).
doi: 10.1212/WNL.48.3.712
Greenberg, S. A., Pinkus, J. L. & Amato, A. A. Nuclear membrane proteins are present within rimmed vacuoles in inclusion-body myositis. Muscle Nerve 34, 406–416 (2006).
doi: 10.1002/mus.20584
Chahin, N. & Engel, A. G. Correlation of muscle biopsy, clinical course, and outcome in PM and sporadic IBM. Neurology 70, 418–424 (2008).
doi: 10.1212/01.wnl.0000277527.69388.fe
Tawara, N. et al. Pathomechanisms of anti-cytosolic 5′-nucleotidase 1 A autoantibodies in sporadic inclusion body myositis. Ann. Neurol. 81, 512–525 (2017).
doi: 10.1002/ana.24919
Johns Hopkins University. Myopathy, myofibrillar, 1; MFM1. OMIM https://www.omim.org/entry/601419 (2014).
Ahmed, M. et al. Targeting protein homeostasis in sporadic inclusion body myositis. Sci. Transl Med. 8, 331ra41 (2016).
doi: 10.1126/scitranslmed.aad4583
pubmed: 5043094
pmcid: 5043094
Sivakumar, K., Semino-Mora, C. & Dalakas, M. C. An inflammatory, familial, inclusion body myositis with autoimmune features and a phenotype identical to sporadic inclusion body myositis. Studies in three families. Brain 120, 653–661 (1997).
pubmed: 9153127
Ranque-Francois, B. et al. Familial inflammatory inclusion body myositis. Ann. Rheum. Dis. 64, 634–637 (2005).
doi: 10.1136/ard.2004.025494
pubmed: 1755454
pmcid: 1755454
Tateyama, M. et al. Familial inclusion body myositis: a report on two Japanese sisters. Intern. Med. 42, 1035–1038 (2003).
doi: 10.2169/internalmedicine.42.1035
Callan, A., Capkun, G., Vasanthaprasad, V., Freitas, R. & Needham, M. A. Systematic review and meta-analysis of prevalence studies of sporadic inclusion body myositis. J. Neuromuscul. Dis. 4, 127–137 (2017).
doi: 10.3233/JND-160198
Tan, J. A. et al. Incidence and prevalence of idiopathic inflammatory myopathies in South Australia: a 30-year epidemiologic study of histology-proven cases. Int. J. Rheum. Dis. 16, 331–338 (2013).
doi: 10.1111/j.1756-185X.2011.01669.x
Badrising, U. A. et al. Epidemiology of inclusion body myositis in the Netherlands: a nationwide study. Neurology 55, 1385–1387 (2000).
doi: 10.1212/WNL.55.9.1385
Lefter, S., Hardiman, O. & Ryan, A. M. A population-based epidemiologic study of adult neuromuscular disease in the Republic of Ireland. Neurology 88, 304–313 (2017).
doi: 10.1212/WNL.0000000000003504
Suzuki, N. et al. Increase in number of sporadic inclusion body myositis (sIBM) in Japan. J. Neurol. 259, 554–556 (2012).
doi: 10.1007/s00415-011-6185-8
Dobloug, G. C. et al. High prevalence of inclusion body myositis in Norway; a population-based clinical epidemiology study. Eur. J. Neurol. 22, 672 (2015).
doi: 10.1111/ene.12627
Suzuki, N. et al. Multicenter questionnaire survey for sporadic inclusion body myositis in Japan. Orphanet J. Rare Dis. 11, 146 (2016).
doi: 10.1186/s13023-016-0524-x
pubmed: 5100251
pmcid: 5100251
Wilson, F. C., Ytterberg, S. R., St Sauver, J. L. & Reed, A. M. Epidemiology of sporadic inclusion body myositis and polymyositis in Olmsted County, Minnesota. J. Rheumatol. 35, 445–447 (2008).
pubmed: 18203321
Chilingaryan, A., Rison, R. A. & Beydoun, S. R. Misdiagnosis of inclusion body myositis: two case reports and a retrospective chart review. J. Med. Case Rep. 9, 169 (2015).
doi: 10.1186/s13256-015-0647-z
pubmed: 4533788
pmcid: 4533788
Paltiel, A. D. et al. Demographic and clinical features of inclusion body myositis in North America. Muscle Nerve 52, 527–533 (2015).
doi: 10.1002/mus.24562
pubmed: 4869122
pmcid: 4869122
Keshishian, A., Greenberg, S. A., Agashivala, N., Baser, O. & Johnson, K. Health care costs and comorbidities for patients with inclusion body myositis. Curr. Med. Res. Opin. 34, 1679–1685 (2018).
doi: 10.1080/03007995.2018.1486294
Ko, E. H. & Rubin, A. D. Dysphagia due to inclusion body myositis: case presentation and review of the literature. Ann. Otol. Rhinol. Laryngol. 123, 605–608 (2014).
doi: 10.1177/0003489414525588
Cox, F. M. et al. Detecting dysphagia in inclusion body myositis. J. Neurol. 256, 2009–2013 (2009).
doi: 10.1007/s00415-009-5229-9
pubmed: 2780610
pmcid: 2780610
Houser, S. M., Calabrese, L. H. & Strome, M. Dysphagia in patients with inclusion body myositis. Laryngoscope 108, 1001–1005 (1998).
doi: 10.1097/00005537-199807000-00009
Oh, T. H., Brumfield, K. A., Hoskin, T. L., Kasperbauer, J. L. & Basford, J. R. Dysphagia in inclusion body myositis: clinical features, management, and clinical outcome. Am. J. Phys. Med. Rehabil. 87, 883–889 (2008).
doi: 10.1097/PHM.0b013e31818a50e2
Riminton, D. S., Chambers, S. T., Parkin, P. J., Pollock, M. & Donaldson, I. M. Inclusion body myositis presenting solely as dysphagia. Neurology 43, 1241–1243 (1993).
doi: 10.1212/WNL.43.6.1241
Verma, A., Bradley, W. G., Adesina, A. M., Sofferman, R. & Pendlebury, W. W. Inclusion body myositis with cricopharyngeus muscle involvement and severe dysphagia. Muscle Nerve 14, 470–473 (1991).
doi: 10.1002/mus.880140514
Rodriguez Cruz, P. M., Needham, M., Hollingsworth, P., Mastaglia, F. L. & Hillman, D. R. Sleep disordered breathing and subclinical impairment of respiratory function are common in sporadic inclusion body myositis. Neuromuscul. Disord. 24, 1036–1041 (2014).
doi: 10.1016/j.nmd.2014.08.003
Brady, S., Squier, W. & Hilton-Jones, D. Clinical assessment determines the diagnosis of inclusion body myositis independently of pathological features. J. Neurol. Neurosurg. Psychiatry 84, 1240–1246 (2013).
doi: 10.1136/jnnp-2013-305690
Dion, E. et al. Magnetic resonance imaging criteria for distinguishing between inclusion body myositis and polymyositis. J. Rheumatol. 29, 1897–1906 (2002).
pubmed: 12233884
Cox, F. M. et al. Magnetic resonance imaging of skeletal muscles in sporadic inclusion body myositis. Rheumatology 50, 1153–1161 (2011).
doi: 10.1093/rheumatology/ker001
Inaishi, Y. et al. MRI for evaluation of flexor digitorum profundus muscle involvement in inclusion body myositis. Can. J. Neurol. Sci. 41, 780–781 (2014).
doi: 10.1017/cjn.2014.35
Tasca, G. et al. Magnetic resonance imaging pattern recognition in sporadic inclusion-body myositis. Muscle Nerve 52, 956–962 (2015).
doi: 10.1002/mus.24661
Guimaraes, J. B. et al. Sporadic inclusion body myositis: MRI findings and correlation with clinical and functional parameters. AJR Am. J. Roentgenol. 209, 1340–1347 (2017).
doi: 10.2214/AJR.17.17849
Tsukita, K., Yagita, K., Sakamaki-Tsukita, H. & Suenaga, T. Sporadic inclusion body myositis: magnetic resonance imaging and ultrasound characteristics. QJM 111, 667–668 (2018).
doi: 10.1093/qjmed/hcy065
Noto, Y. et al. Contrasting echogenicity in flexor digitorum profundus-flexor carpi ulnaris: a diagnostic ultrasound pattern in sporadic inclusion body myositis. Muscle Nerve 49, 745–748 (2014).
doi: 10.1002/mus.24056
Nodera, H. et al. Intramuscular dissociation of echogenicity in the triceps surae characterizes sporadic inclusion body myositis. Eur. J. Neurol. 23, 588–596 (2016).
doi: 10.1111/ene.12899
Albayda, J. et al. Pattern of muscle involvement in inclusion body myositis: a sonographic study. Clin. Exp. Rheumatol. 36, 996–1002 (2018).
pubmed: 29745890
Bachasson, D., Dubois, G. J. R., Allenbach, Y., Benveniste, O. & Hogrel, J. Y. Muscle shear wave elastography in inclusion body myositis: feasibility, reliability and relationships with muscle impairments. Ultrasound Med. Biol. 44, 1423–1432 (2018).
doi: 10.1016/j.ultrasmedbio.2018.03.026
Olthoff, A. et al. Evaluation of dysphagia by novel real-time MRI. Neurology 87, 2132–2138 (2016).
doi: 10.1212/WNL.0000000000003337
Koffman, B. M., Rugiero, M. & Dalakas, M. C. Immune-mediated conditions and antibodies associated with sporadic inclusion body myositis. Muscle Nerve 21, 115–117 (1998).
doi: 10.1002/(SICI)1097-4598(199801)21:1<115::AID-MUS15>3.0.CO;2-2
Greenberg, S. A. Cytoplasmic 5′-nucleotidase autoantibodies in inclusion body myositis: Isotypes and diagnostic utility. Muscle Nerve 50, 488–492 (2014).
doi: 10.1002/mus.24199
Goyal, N. A. et al. Seropositivity for NT5c1A antibody in sporadic inclusion body myositis predicts more severe motor, bulbar and respiratory involvement. J. Neurol. Neurosurg. Psychiatry 87, 373–378 (2016).
doi: 10.1136/jnnp-2014-310008
Lloyd, T. E. et al. Cytosolic 5′-nucleotidase 1A as a target of circulating autoantibodies in autoimmune diseases. Arthritis Care Res. 68, 66–71 (2016).
doi: 10.1002/acr.22600
Kramp, S. L. et al. Development and evaluation of a standardized ELISA for the determination of autoantibodies against cN-1A (Mup44, NT5C1A) in sporadic inclusion body myositis. Auto Immun. Highlights 7, 16 (2016).
doi: 10.1007/s13317-016-0088-8
pubmed: 5114199
pmcid: 5114199
Felice, K. J. et al. Sensitivity and clinical utility of the anti-cytosolic 5’-nucleotidase 1 A (cN1A) antibody test in sporadic inclusion body myositis: Report of 40 patients from a single neuromuscular center. Neuromuscul. Disord. 28, 600–664 (2018).
Herbert, M. K. et al. Disease specificity of autoantibodies to cytosolic 5′-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases. Ann. Rheum. Dis. 75, 696–701 (2016).
doi: 10.1136/annrheumdis-2014-206691
Muro, Y., Nakanishi, H., Katsuno, M., Kono, M. & Akiyama, M. Prevalence of anti-NT5C1A antibodies in Japanese patients with autoimmune rheumatic diseases in comparison with other patient cohorts. Clin. Chim. Acta 472, 1–4 (2017).
doi: 10.1016/j.cca.2017.07.002
Rietveld, A. et al. Autoantibodies to cytosolic 5′-nucleotidase 1A in primary Sjögren’s syndrome and systemic lupus erythematosus. Front. Immunol. 9, 1200 (2018).
doi: 10.3389/fimmu.2018.01200
pubmed: 5996144
pmcid: 5996144
Mhiri, C. & Gherardi, R. Inclusion body myositis in French patients. A clinicopathological evaluation. Neuropathol. Appl. Neurobiol. 16, 333–344 (1990).
doi: 10.1111/j.1365-2990.1990.tb01267.x
Askanas, V. & Engel, W. K. Molecular pathology and pathogenesis of inclusion-body myositis. Microsc. Res. Tech. 67, 114–120 (2005).
doi: 10.1002/jemt.20186
Rodriguez Cruz, P. M. et al. An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies. Neuromuscul. Disord. 24, 1025–1035 (2014).
doi: 10.1016/j.nmd.2014.06.436
Ikenaga, C. et al. Clinicopathologic features of myositis patients with CD8-MHC-1 complex pathology. Neurology 89, 1060–1068 (2017).
doi: 10.1212/WNL.0000000000004333
Temiz, P., Weihl, C. C. & Pestronk, A. Inflammatory myopathies with mitochondrial pathology and protein aggregates. J. Neurol. Sci. 278, 25–29 (2009).
doi: 10.1016/j.jns.2008.11.010
Pestronk, A. Acquired immune and inflammatory myopathies: pathologic classification. Curr. Opin. Rheumatol. 23, 595–604 (2011).
doi: 10.1097/BOR.0b013e32834bab42
van der Meulen, M. F. et al. Rimmed vacuoles and the added value of SMI-31 staining in diagnosing sporadic inclusion body myositis. Neuromuscul. Disord. 11, 447–451 (2001).
doi: 10.1016/S0960-8966(00)00219-4
Dalakas, M. C. Polymyositis, dermatomyositis and inclusion-body myositis. N. Engl. J. Med. 325, 1487–1498 (1991).
doi: 10.1056/NEJM199111213252107
Mastaglia, F. L. & Phillips, B. A. Idiopathic inflammatory myopathies: epidemiology, classification, and diagnostic criteria. Rheum. Dis. Clin. North Am. 28, 723–741 (2002).
doi: 10.1016/S0889-857X(02)00021-2
Tawil, R. & Griggs, R. C. Inclusion body myositis. Curr. Opin. Rheumatol. 14, 653–657 (2002).
doi: 10.1097/00002281-200211000-00004
Verschuuren, J. J., van Engelen, B. G. M., van der Hoeven, H. & Hoogendijk, J. Inclusion body myositis diagnostic criteria. Inclusion Body Myositis. http://ibmmyositis.com/emery81.pdf (1997).
Griggs, R. C. et al. Inclusion body myositis and myopathies. Ann. Neurol. 38, 705–713 (1995).
doi: 10.1002/ana.410380504
Hilton-Jones, D. et al. Inclusion body myositis: MRC Centre for Neuromuscular Diseases, IBM workshop, London, 13 June 2008. Neuromuscul Disord. 20, 142–147 (2010).
doi: 10.1016/j.nmd.2009.11.003
Benveniste, O. & Hilton-Jones, D. International Workshop on Inclusion Body Myositis held at the Institute of Myology, Paris, on 29 May 2009. Neuromuscul. Disord. 20, 414–421 (2010).
doi: 10.1016/j.nmd.2010.03.014
Rose, M. R. 188th ENMC International Workshop: Inclusion Body Myositis, 2–4 December 2011, Naarden, The Netherlands. Neuromuscul. Disord. 23, 1044–1055 (2013).
doi: 10.1016/j.nmd.2013.08.007
Lloyd, T. E. et al. Evaluation and construction of diagnostic criteria for inclusion body myositis. Neurology 83, 426–433 (2014).
doi: 10.1212/WNL.0000000000000642
pubmed: 4132572
pmcid: 4132572
Kanellopoulos, P., Baltoyiannis, C. & Tzioufas, A. G. Primary Sjögren’s syndrome associated with inclusion body myositis. Rheumatology 41, 440–444 (2002).
doi: 10.1093/rheumatology/41.4.440
Misterska-Skora, M., Sebastian, A., Dziegiel, P., Sebastian, M. & Wiland, P. Inclusion body myositis associated with Sjögren’s syndrome. Rheumatol. Int. 33, 3083–3086 (2013).
doi: 10.1007/s00296-012-2556-4
Colafrancesco, S. et al. Myositis in primary Sjögren’s syndrome: data from a multicentre cohort. Clin. Exp. Rheumatol. 33, 457–464 (2015).
pubmed: 26088683
Lloyd, T. E. et al. Overlapping features of polymyositis and inclusion body myositis in HIV-infected patients. Neurology 88, 1454–1460 (2017).
doi: 10.1212/WNL.0000000000003821
pubmed: 5386438
pmcid: 5386438
Hiniker, A., Daniels, B. H. & Margeta, M. T-cell-mediated inflammatory myopathies in HIV-positive individuals: a histologic study of 19 cases. J. Neuropathol. Exp. Neurol. 75, 239–245 (2016).
doi: 10.1093/jnen/nlv023
pubmed: 5009472
pmcid: 5009472
Cupler, E. J. et al. Inclusion body myositis in HIV-1 and HTLV-1 infected patients. Brain 119, 1887–1893 (1996).
doi: 10.1093/brain/119.6.1887
Couture, P. et al. Inclusion body myositis and human immunodeficiency virus type 1: a new case report and literature review. Neuromuscul. Disord. 28, 334–338 (2018).
doi: 10.1016/j.nmd.2018.01.005
Matsuura, E. et al. Inclusion body myositis associated with human T-lymphotropic virus-type I infection: eleven patients from an endemic area in Japan. J. Neuropathol. Exp. Neurol. 67, 41–49 (2008).
doi: 10.1097/nen.0b013e31815f38b7
Cox, F. M. et al. The heart in sporadic inclusion body myositis: a study in 51 patients. J. Neurol. 257, 447–451 (2010).
doi: 10.1007/s00415-009-5350-9
Limaye, V. S., Lester, S., Blumbergs, P. & Roberts-Thomson, P. J. Idiopathic inflammatory myositis is associated with a high incidence of hypertension and diabetes mellitus. Int. J. Rheum. Dis. 13, 132–137 (2010).
doi: 10.1111/j.1756-185X.2010.01470.x
Lai, Y. T. et al. Dermatomyositis is associated with an increased risk of cardiovascular and cerebrovascular events: a Taiwanese population-based longitudinal follow-up study. Br. J. Dermatol. 168, 1054–1059 (2013).
doi: 10.1111/bjd.12245
Wang, H., Tang, J., Chen, X., Li, F. & Luo, J. Lipid profiles in untreated patients with dermatomyositis. J. Eur. Acad. Dermatol. Venereol. 27, 175–179 (2013).
doi: 10.1111/j.1468-3083.2011.04437.x
Wang, H. et al. Altered lipid levels in untreated patients with early polymyositis. PLOS ONE 9, e89827 (2014).
doi: 10.1371/journal.pone.0089827
pubmed: 3933648
pmcid: 3933648
Diederichsen, L. P. et al. Traditional cardiovascular risk factors and coronary artery calcification in adults with polymyositis and dermatomyositis: a Danish multicenter study. Arthritis Care Res. 67, 848–854 (2015).
doi: 10.1002/acr.22520
Rai, S. K., Choi, H. K., Sayre, E. C. & Avina-Zubieta, J. A. Risk of myocardial infarction and ischaemic stroke in adults with polymyositis and dermatomyositis: a general population-based study. Rheumatology 55, 461–469 (2016).
pubmed: 26424835
Sherer, Y. & Shoenfeld, Y. Mechanisms of disease: atherosclerosis in autoimmune diseases. Nat. Clin. Pract. Rheumatol. 2, 99–106 (2006).
doi: 10.1038/ncprheum0092
Ahearn, J., Shields, K. J., Liu, C. C. & Manzi, S. Cardiovascular disease biomarkers across autoimmune diseases. Clin. Immunol. 161, 59–63 (2015).
doi: 10.1016/j.clim.2015.05.024
Alexanderson, H. Exercise in inflammatory myopathies, including inclusion body myositis. Curr. Rheumatol. Rep. 14, 244–251 (2012).
doi: 10.1007/s11926-012-0248-4
Arnardottir, S., Alexanderson, H., Lundberg, I. E. & Borg, K. Sporadic inclusion body myositis: pilot study on the effects of a home exercise program on muscle function, histopathology and inflammatory reaction. J. Rehabil. Med. 35, 31–35 (2003).
doi: 10.1080/16501970306110
Johnson, L. G., Edwards, D. J., Walters, S. E., Thickbroom, G. W. & Mastaglia, F. L. The effectiveness of an individualized, home-based functional exercise program for patients with sporadic inclusion body myositis. J. Clin. Neuromuscul. Dis. 8, 187–194 (2007).
doi: 10.1097/CND.0b013e3181237291
Parker, K. C. et al. Fast-twitch sarcomeric and glycolytic enzyme protein loss in inclusion body myositis. Muscle Nerve 39, 739–753 (2009).
doi: 10.1002/mus.21230
pubmed: 2753483
pmcid: 2753483
Cherin, P. et al. Intravenous immunoglobulin for dysphagia of inclusion body myositis. Neurology 58, 326 (2002).
doi: 10.1212/WNL.58.2.326
Pars, K. et al. Subcutaneous immunoglobulin treatment of inclusion-body myositis stabilizes dysphagia. Muscle Nerve 48, 838–839 (2013).
doi: 10.1002/mus.23895
Cherin, P., Delain, J. C., de Jaeger, C. & Crave, J. C. Subcutaneous immunoglobulin use in inclusion body myositis: a review of 6 cases. Case Rep. Neurol. 7, 227–232 (2015).
doi: 10.1159/000441490
pubmed: 4649754
pmcid: 4649754
Mendell, J. R. et al. Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes. Mol. Ther. 25, 870–879 (2017).
doi: 10.1016/j.ymthe.2017.02.015
pubmed: 5383643
pmcid: 5383643
Greenberg, S. A. Unfounded claims of improved functional outcomes attributed to follistatin gene therapy in inclusion body myositis. Mol. Ther. 25, 2235–2237 (2017).
doi: 10.1016/j.ymthe.2017.09.002
pubmed: 5628928
pmcid: 5628928
Walter, M. C. et al. High-dose immunoglobulin therapy in sporadic inclusion body myositis: a double-blind, placebo-controlled study. J. Neurol. 247, 22–28 (2000).
doi: 10.1007/s004150050005
Dalakas, M. C. et al. A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology 56, 323–327 (2001).
doi: 10.1212/WNL.56.3.323
Badrising, U. A. et al. Comparison of weakness progression in inclusion body myositis during treatment with methotrexate or placebo. Ann. Neurol. 51, 369–372 (2002).
doi: 10.1002/ana.10121
Muscle Study, G. Randomized pilot trial of βINF1a (Avonex) in patients with inclusion body myositis. Neurology 57, 1566–1570 (2001).
doi: 10.1212/WNL.57.9.1566
Muscle Study, G. Randomized pilot trial of high-dose βINF-1a in patients with inclusion body myositis. Neurology 63, 718–720 (2004).
doi: 10.1212/01.WNL.0000134675.98525.79
Rutkove, S. B. et al. A pilot randomized trial of oxandrolone in inclusion body myositis. Neurology 58, 1081–1087 (2002).
doi: 10.1212/WNL.58.7.1081
Amato, A. A. et al. Treatment of sporadic inclusion body myositis with bimagrumab. Neurology 83, 2239–2246 (2014).
doi: 10.1212/WNL.0000000000001070
pubmed: 25381300
pmcid: 25381300
Amato, A. A. et al. A randomized, double-blind, placebo-controlled study of bimagrumab in patients with sporadic inclusion body myositis [abstract 8L]. Arthritis Rheumatol. 68, 4367–4369 (2016).
Chou, S. M. Myxovirus-like structures and accompanying nuclear changes in chronic polymyositis. Arch. Pathol. 86, 649–658 (1968).
pubmed: 5701638
Rifai, Z., Welle, S., Kamp, C. & Thornton, C. A. Ragged red fibers in normal aging and inflammatory myopathy. Ann. Neurol. 37, 24–29 (1995).
doi: 10.1002/ana.410370107
Oldfors, A. et al. Mitochondrial abnormalities in inclusion-body myositis. Neurology 66, S49–S55 (2006).
doi: 10.1212/01.wnl.0000192127.63013.8d
Askanas, V., Serdaroglu, P., Engel, W. K. & Alvarez, R. B. Immunolocalization of ubiquitin in muscle biopsies of patients with inclusion body myositis and oculopharyngeal muscular dystrophy. Neurosci. Lett. 130, 73–76 (1991).
doi: 10.1016/0304-3940(91)90230-Q
Askanas, V., Engel, W. K. & Alvarez, R. B. Light and electron microscopic localization of β-amyloid protein in muscle biopsies of patients with inclusion-body myositis. Am. J. Pathol. 141, 31–36 (1992).
pubmed: 1886568
pmcid: 1886568
Askanas, V., Engel, W. K., Bilak, M., Alvarez, R. B. & Selkoe, D. J. Twisted tubulofilaments of inclusion body myositis muscle resemble paired helical filaments of Alzheimer brain and contain hyperphosphorylated tau. Am. J. Pathol. 144, 177–187 (1994).
pubmed: 1887131
pmcid: 1887131
Greenberg, S. A. Theories of the pathogenesis of inclusion body myositis. Curr. Rheumatol. Rep. 12, 221–228 (2010).
doi: 10.1007/s11926-010-0102-5
pubmed: 2929917
pmcid: 2929917
Askanas, V. & Engel, W. K. Proposed pathogenetic cascade of inclusion-body myositis: importance of amyloid-β, misfolded proteins, predisposing genes, and aging. Curr. Opin. Rheumatol. 15, 737–744 (2003).
doi: 10.1097/00002281-200311000-00009
Askanas, V. & Engel, W. K. Inclusion-body myositis: a myodegenerative conformational disorder associated with Aβ, protein misfolding, and proteasome inhibition. Neurology 66, S39–S48 (2006).
doi: 10.1212/01.wnl.0000192128.13875.1e
Askanas, V., Engel, W. K. & Nogalska, A. Sporadic inclusion-body myositis: a degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy. Biochim. Biophys. Acta 1852, 633–643 (2015).
doi: 10.1016/j.bbadis.2014.09.005
Greenberg, S. A. How citation distortions create unfounded authority: analysis of a citation network. BMJ 339, b2680 (2009).
doi: 10.1136/bmj.b2680
pubmed: 2714656
pmcid: 2714656
Fergusson, D. Inappropriate referencing in research. BMJ 339, b2049 (2009).
doi: 10.1136/bmj.b2049
Sarkozi, E., Askanas, V., Johnson, S. A., McFerrin, J. & Engel, W. K. Expression of β-amyloid precursor protein gene is developmentally regulated in human muscle fibers in vivo and in vitro. Exp. Neurol. 128, 27–33 (1994).
doi: 10.1006/exnr.1994.1109
Askanas, V. & Engel, W. K. Sporadic inclusion-body myositis: conformational multifactorial ageing-related degenerative muscle disease associated with proteasomal and lysosomal inhibition, endoplasmic reticulum stress, and accumulation of amyloid-β42 oligomers and phosphorylated tau. Presse Med. 40, e219–e235 (2011).
doi: 10.1016/j.lpm.2010.11.024
Salajegheh, M. et al. Nature of “Tau” immunoreactivity in normal myonuclei and inclusion body myositis. Muscle Nerve 40, 520–528 (2009).
doi: 10.1002/mus.21471
Pruitt, J. N. 2nd, Showalter, C. J. & Engel, A. G. Sporadic inclusion body myositis: counts of different types of abnormal fibers. Ann. Neurol. 39, 139–143 (1996).
doi: 10.1002/ana.410390122
Banwell, B. L. & Engel, A. G. αB-Crystallin immunolocalization yields new insights into inclusion body myositis. Neurology 54, 1033–1041 (2000).
doi: 10.1212/WNL.54.5.1033
Sherriff, F. E., Joachim, C. L., Squier, M. V. & Esiri, M. M. Ubiquitinated inclusions in inclusion-body myositis patients are immunoreactive for cathepsin D but not β-amyloid. Neurosci. Lett. 194, 37–40 (1995).
doi: 10.1016/0304-3940(95)11718-C
Dubourg, O. et al. Diagnostic value of markers of muscle degeneration in sporadic inclusion body myositis. Acta Myol 30, 103–108 (2011).
pubmed: 3235833
pmcid: 3235833
Hiniker, A., Daniels, B. H., Lee, H. S. & Margeta, M. Comparative utility of LC3, p62 and TDP-43 immunohistochemistry in differentiation of inclusion body myositis from polymyositis and related inflammatory myopathies. Acta Neuropathol. Commun. 1, 29 (2013).
doi: 10.1186/2051-5960-1-29
pubmed: 3893502
pmcid: 3893502
Vattemi, G., Engel, W. K., McFerrin, J. & Askanas, V. Endoplasmic reticulum stress and unfolded protein response in inclusion body myositis muscle. Am. J. Pathol. 164, 1–7 (2004).
doi: 10.1016/S0002-9440(10)63089-1
pubmed: 1602240
pmcid: 1602240
Lunemann, J. D. et al. β-amyloid is a substrate of autophagy in sporadic inclusion body myositis. Ann. Neurol. 61, 476–483 (2007).
doi: 10.1002/ana.21115
Nakano, S., Oki, M. & Kusaka, H. The role of p62/SQSTM1 in sporadic inclusion body myositis. Neuromuscul. Disord. 27, 363–369 (2017).
doi: 10.1016/j.nmd.2016.12.009
Pinkus, J. L., Amato, A. A., Taylor, J. P. & Greenberg, S. A. Abnormal distribution of heterogeneous nuclear ribonucleoproteins in sporadic inclusion body myositis. Neuromuscul. Disord. 24, 611–616 (2014).
doi: 10.1016/j.nmd.2014.04.012
Weihl, C. C. et al. TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia. J. Neurol. Neurosurg. Psychiatry 79, 1186–1189 (2008).
doi: 10.1136/jnnp.2007.131334
pubmed: 2586594
pmcid: 2586594
Salajegheh, M. et al. Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis. Muscle Nerve 40, 19–31 (2009).
doi: 10.1002/mus.21386
pubmed: 2700211
pmcid: 2700211
Nogalska, A., Terracciano, C., D’Agostino, C., King Engel, W. & Askanas, V. p62/SQSTM1 is overexpressed and prominently accumulated in inclusions of sporadic inclusion-body myositis muscle fibers, and can help differentiating it from polymyositis and dermatomyositis. Acta Neuropathol. 118, 407–413 (2009).
doi: 10.1007/s00401-009-0564-6
Hengstman, G. J. & van Engelen, B. G. Polymyositis invasion of non-necrotic muscle fibres, and the art of repetition. BMJ 329, 1464–1467 (2004).
doi: 10.1136/bmj.329.7480.1464
pubmed: 535982
pmcid: 535982
Callender, L. A. et al. Human CD8
doi: 10.1111/acel.12675
Chong, L. K. et al. Proliferation and interleukin 5 production by CD8
doi: 10.1002/eji.200737687
pubmed: 2843081
pmcid: 2843081
Henson, S. M. & Akbar, A. N. KLRG1—more than a marker for T cell senescence. Age 31, 285–291 (2009).
doi: 10.1007/s11357-009-9100-9
pubmed: 2813054
pmcid: 2813054
Akbar, A. N. & Henson, S. M. Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nat. Rev. Immunol. 11, 289–295 (2011).
doi: 10.1038/nri2959
Melis, L., Van Praet, L., Pircher, H., Venken, K. & Elewaut, D. Senescence marker killer cell lectin-like receptor G1 (KLRG1) contributes to TNF-α production by interaction with its soluble E-cadherin ligand in chronically inflamed joints. Ann. Rheum. Dis. 73, 1223–1231 (2014).
doi: 10.1136/annrheumdis-2013-203881
Dumitriu, I. E. The life (and death) of CD4
doi: 10.1111/imm.12506
pubmed: 4582960
pmcid: 4582960
Maly, K. & Schirmer, M. The story of CD4
pubmed: 4365319
pmcid: 4365319
Lima, X. T. et al. Frequency and characteristics of circulating CD4
doi: 10.1111/bjd.13993
Schirmer, M., Vallejo, A. N., Weyand, C. M. & Goronzy, J. J. Resistance to apoptosis and elevated expression of Bcl-2 in clonally expanded CD4
pubmed: 9670983
Schirmer, M. et al. Circulating cytotoxic CD8
doi: 10.1186/ar386
Liaskou, E. et al. Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis. Gastroenterology 147, 221–232 (2014).
doi: 10.1053/j.gastro.2014.04.003
pubmed: 4961260
pmcid: 4961260
Dejaco, C. et al. NKG2D stimulated T cell autoreactivity in giant cell arteritis and polymyalgia rheumatica. Ann. Rheum. Dis. 72, 1852–1859 (2013).
doi: 10.1136/annrheumdis-2012-201660
Dejaco, C., Duftner, C., Klauser, A. & Schirmer, M. Altered T cell subtypes in spondyloarthritis, rheumatoid arthritis and polymyalgia rheumatica. Rheumatol. Int. 30, 297–303 (2010).
doi: 10.1007/s00296-009-0949-9
Duftner, C. et al. Prevalence, clinical relevance and characterization of circulating cytotoxic CD4
doi: 10.1186/ar793
pubmed: 193730
pmcid: 193730
Pinto-Medel, M. J. et al. The CD4
doi: 10.1016/j.jneuroim.2011.11.008
Garcia de Tena, J. et al. Active Crohn’s disease patients show a distinctive expansion of circulating memory CD4
doi: 10.1023/B:JOCI.0000019784.20191.7f
Leblanc, F., Zhang, D., Liu, X. & Loughran, T. P. Large granular lymphocyte leukemia: from dysregulated pathways to therapeutic targets. Future Oncol. 8, 787–801 (2012).
doi: 10.2217/fon.12.75
pubmed: 3464048
pmcid: 3464048
Mastaglia, F. L. et al. Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms. Neuromuscul. Disord. 23, 969–974 (2013).
doi: 10.1016/j.nmd.2013.09.008
Gang, Q. et al. The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis. Neurobiol. Aging 36, 1766.e1–1766.e3 (2015).
doi: 10.1016/j.neurobiolaging.2014.12.039
De Paepe, B. & De Bleecker, J. L. The nonnecrotic invaded muscle fibers of polymyositis and sporadic inclusion body myositis: on the interplay of chemokines and stress proteins. Neurosci. Lett. 535, 18–23 (2013).
doi: 10.1016/j.neulet.2012.11.064
De Paepe, B., Creus, K. K. & De Bleecker, J. L. Chemokines in idiopathic inflammatory myopathies. Front. Biosci. 13, 2548–2577 (2008).
doi: 10.2741/2866
Ivanidze, J. et al. Inclusion body myositis: laser microdissection reveals differential up-regulation of IFN-γ signaling cascade in attacked versus nonattacked myofibers. Am. J. Pathol. 179, 1347–1359 (2011).
doi: 10.1016/j.ajpath.2011.05.055
pubmed: 3157228
pmcid: 3157228
Mammen, A. L. Autoimmune myopathies. Continuum 22, 1852–1870 (2016).
pubmed: 27922497
Mammen, A. L. Autoimmune myopathies: autoantibodies, phenotypes and pathogenesis. Nat. Rev. Neurol. 7, 343–354 (2011).
doi: 10.1038/nrneurol.2011.63
Mammen, A. L. Which nonautoimmune myopathies are most frequently misdiagnosed as myositis? Curr. Opin. Rheumatol. 29, 618–622 (2017).
pubmed: 5814131
pmcid: 5814131
Britson, K. A., Yang, S. Y. & Lloyd, T. E. New developments in the genetics of inclusion body myositis. Curr. Rheumatol. Rep. 20, 26 (2018).
doi: 10.1007/s11926-018-0738-0
pubmed: 6374100
pmcid: 6374100
Olive, M. et al. Expression of mutant ubiquitin (UBB
pubmed: 17931355
Olive, M. et al. TAR DNA-binding protein 43 accumulation in protein aggregate myopathies. J. Neuropathol. Exp. Neurol. 68, 262–273 (2009).
doi: 10.1097/NEN.0b013e3181996d8f
Duleh, S., Wang, X., Komirenko, A. & Margeta, M. Activation of the Keap1/Nrf2 stress response pathway in autophagic vacuolar myopathies. Acta Neuropathol. Commun. 4, 115 (2016).
doi: 10.1186/s40478-016-0384-6
pubmed: 5088660
pmcid: 5088660
Arahata, K. et al. Inflammatory response in facioscapulohumeral muscular dystrophy (FSHD): immunocytochemical and genetic analyses. Muscle Nerve Suppl. 2, S56–S66 (1995).
doi: 10.1002/mus.880181312
Gallardo, E. et al. Inflammation in dysferlin myopathy: immunohistochemical characterization of 13 patients. Neurology 57, 2136–2138 (2001).
doi: 10.1212/WNL.57.11.2136
Castets, P., Frank, S., Sinnreich, M. & Ruegg, M. A. “Get the balance right”: pathological significance of autophagy perturbation in neuromuscular disorders. J. Neuromuscul. Dis. 3, 127–155 (2016).
doi: 10.3233/JND-160153
pubmed: 5271579
pmcid: 5271579
Varadhachary, A. S., Weihl, C. C. & Pestronk, A. Mitochondrial pathology in immune and inflammatory myopathies. Curr. Opin. Rheumatol. 22, 651–657 (2010).
doi: 10.1097/BOR.0b013e32833f108a
Meyer, A. et al. IFN-β-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis. Acta Neuropathol. 134, 655–666 (2017).
doi: 10.1007/s00401-017-1731-9
Nathan, J. A. et al. Immuno- and constitutive proteasomes do not differ in their abilities to degrade ubiquitinated proteins. Cell 152, 1184–1194 (2013).
doi: 10.1016/j.cell.2013.01.037
pubmed: 3791394
pmcid: 3791394
Seifert, U. et al. Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress. Cell 142, 613–624 (2010).
doi: 10.1016/j.cell.2010.07.036
Nagaraju, K. et al. Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction. Arthritis Rheum. 52, 1824–1835 (2005).
doi: 10.1002/art.21103
Correia, A. S., Patel, P., Dutta, K. & Julien, J. P. Inflammation induces TDP-43 mislocalization and aggregation. PLOS ONE 10, e0140248 (2015).
doi: 10.1371/journal.pone.0140248
pubmed: 4596857
pmcid: 4596857
Zhong, Z. et al. NF-κB restricts inflammasome activation via elimination of damaged mitochondria. Cell 164, 896–910 (2016).
doi: 10.1016/j.cell.2015.12.057
pubmed: 26919428
pmcid: 26919428
Ozden, S. et al. Direct evidence for a chronic CD8
doi: 10.1128/JVI.78.19.10320-10327.2004
pubmed: 516372
pmcid: 516372
Green, D. R., Droin, N. & Pinkoski, M. Activation-induced cell death in T cells. Immunol. Rev. 193, 70–81 (2003).
doi: 10.1034/j.1600-065X.2003.00051.x
Vallejo, A. N., Schirmer, M., Weyand, C. M. & Goronzy, J. J. Clonality and longevity of CD4
doi: 10.4049/jimmunol.165.11.6301
Spaulding, C., Guo, W. & Effros, R. B. Resistance to apoptosis in human CD8
doi: 10.1016/S0531-5565(99)00033-9
Posnett, D. N., Edinger, J. W., Manavalan, J. S., Irwin, C. & Marodon, G. Differentiation of human CD8 T cells: implications for in vivo persistence of CD8
doi: 10.1093/intimm/11.2.229
Hodge, G. & Hodge, S. Steroid resistant CD8
doi: 10.3389/fimmu.2016.00617
pubmed: 5165019
pmcid: 5165019
Pandya, J. M. et al. Effects of conventional immunosuppressive treatment on CD244
doi: 10.1186/s13075-016-0974-5
pubmed: 4818535
pmcid: 4818535
Pearl, J. P. et al. Immunocompetent T cells with a memory-like phenotype are the dominant cell type following antibody-mediated T cell depletion. Am. J. Transplant. 5, 465–474 (2005).
doi: 10.1111/j.1600-6143.2005.00759.x
Olnes, M. J. et al. Effects of systemically administered hydrocortisone on the human immunome. Sci. Rep. 6, 23002 (2016).
doi: 10.1038/srep23002
pubmed: 4789739
pmcid: 4789739
Bohan, A. & Peter, J. B. Polymyositis and dermatomyositis (first of two parts). N. Engl. J. Med. 292, 344–347 (1975).
doi: 10.1056/NEJM197502132920706
Shah, M. V. et al. Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes. Blood 112, 770–781 (2008).
doi: 10.1182/blood-2007-11-121871
pubmed: 18477771
pmcid: 2481553
Bareau, B. et al. Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases. Haematologica 95, 1534–1541 (2010).
doi: 10.3324/haematol.2009.018481
pubmed: 20378561
pmcid: 2930955
Dumitriu, B. et al. Alemtuzumab in T cell large granular lymphocytic leukaemia: interim results from a single-arm, open-label, phase 2 study. Lancet Haematol. 3, e22–e29 (2016).
doi: 10.1016/S2352-3026(15)00227-6
Mohan, S. R. et al. Therapeutic implications of variable expression of CD52 on clonal cytotoxic T cells in CD8
doi: 10.3324/haematol.2009.009191
pubmed: 2754957
pmcid: 2754957
Gitelman, S. E. et al. Antithymocyte globulin therapy for patients with recent-onset type 1 diabetes: 2 year results of a randomised trial. Diabetologia 59, 1153–1161 (2016).
doi: 10.1007/s00125-016-3917-4
pubmed: 4869699
pmcid: 4869699
Scarsi, M. et al. The number of circulating recent thymic emigrants is severely reduced 1 year after a single dose of alemtuzumab in renal transplant recipients. Transpl. Int. 23, 786–795 (2010).
doi: 10.1111/j.1432-2277.2010.01052.x
Neujahr, D. C. et al. Accelerated memory cell homeostasis during T cell depletion and approaches to overcome it. J. Immunol. 176, 4632–4639 (2006).
doi: 10.4049/jimmunol.176.8.4632
Crepin, T. et al. ATG-induced accelerated immune senescence: clinical implications in renal transplant recipients. Am. J. Transplant. 15, 1028–1038 (2015).
doi: 10.1111/ajt.13092
Macedo, C. et al. Long-term effects of alemtuzumab on regulatory and memory T cell subsets in kidney transplantation. Transplantation 93, 813–821 (2012).
doi: 10.1097/TP.0b013e318247a717
pubmed: 3323763
pmcid: 3323763
Ramos-Casals, M. & Brito-Zeron, P. Emerging biological therapies in primary Sjögren’s syndrome. Rheumatology 46, 1389–1396 (2007).
doi: 10.1093/rheumatology/kem078
Lombard, M. et al. Cyclosporin A treatment in primary biliary cirrhosis: results of a long-term placebo controlled trial. Gastroenterology 104, 519–526 (1993).
doi: 10.1016/0016-5085(93)90422-9
Mitchison, H. C. et al. A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss. Hepatology 10, 420–429 (1989).
doi: 10.1002/hep.1840100405
Wiesner, R. H. et al. A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis. N. Engl. J. Med. 322, 1419–1424 (1990).
doi: 10.1056/NEJM199005173222003
Fujihara, T. et al. Preferential localization of CD8
pubmed: 10438965
Kita, H. Autoreactive CD8-specific T cell response in primary biliary cirrhosis. Hepatol. Res. 37 (Suppl. 3), 402–405 (2007).
doi: 10.1111/j.1872-034X.2007.00238.x
Si, L., Whiteside, T. L., Schade, R. R., Starzl, T. E. & Van Thiel, D. H. T-Lymphocyte subsets in liver tissues of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls. J. Clin. Immunol. 4, 262–272 (1984).
doi: 10.1007/BF00915293
pubmed: 3095831
pmcid: 3095831
Bjorkland, A. et al. Blood and liver-infiltrating lymphocytes in primary biliary cirrhosis: increase in activated T and natural killer cells and recruitment of primed memory T cells. Hepatology 13, 1106–1111 (1991).
pubmed: 2050330
Tasaki, S. et al. Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren’s syndrome. Ann. Rheum. Dis. 76, 1458–1466 (2017).
doi: 10.1136/annrheumdis-2016-210788
pubmed: 5738597
pmcid: 5738597
Tsuda, M. et al. Fine phenotypic and functional characterization of effector cluster of differentiation 8 positive T cells in human patients with primary biliary cirrhosis. Hepatology 54, 1293–1302 (2011).
doi: 10.1002/hep.24526
pubmed: 3184190
pmcid: 3184190
Yang, Z., Goronzy, J. J. & Weyand, C. M. Autophagy in autoimmune disease. J. Mol. Med. 93, 707–717 (2015).
doi: 10.1007/s00109-015-1297-8
pubmed: 4486076
pmcid: 4486076
Hosomi, S., Kaser, A. & Blumberg, R. S. Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease. Curr. Opin. Gastroenterol. 31, 81–88 (2015).
doi: 10.1097/MOG.0000000000000144
pubmed: 4592163
pmcid: 4592163
Grootjans, J., Kaser, A., Kaufman, R. J. & Blumberg, R. S. The unfolded protein response in immunity and inflammation. Nat. Rev. Immunol. 16, 469–484 (2016).
doi: 10.1038/nri.2016.62
pubmed: 5310224
pmcid: 5310224
Sasaki, M., Miyakoshi, M., Sato, Y. & Nakanuma, Y. A possible involvement of p62/sequestosome-1 in the process of biliary epithelial autophagy and senescence in primary biliary cirrhosis. Liver Int. 32, 487–499 (2012).
pubmed: 22098537
Sasaki, M., Miyakoshi, M., Sato, Y. & Nakanuma, Y. Autophagy mediates the process of cellular senescence characterizing bile duct damages in primary biliary cirrhosis. Lab. Invest. 90, 835–843 (2010).
doi: 10.1038/labinvest.2010.56
Sasaki, M., Yoshimura-Miyakoshi, M., Sato, Y. & Nakanuma, Y. A possible involvement of endoplasmic reticulum stress in biliary epithelial autophagy and senescence in primary biliary cirrhosis. J. Gastroenterol. 50, 984–995 (2015).
doi: 10.1007/s00535-014-1033-0
Katsiougiannis, S., Tenta, R. & Skopouli, F. N. Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular redistribution of the autoantigens Ro/Sjögren’s syndrome-related antigen A (SSA) and La/SSB in salivary gland epithelial cells. Clin. Exp. Immunol. 181, 244–252 (2015).
doi: 10.1111/cei.12638
pubmed: 4516440
pmcid: 4516440
Leff, R. L., Miller, F. W., Hicks, J., Fraser, D. D. & Plotz, P. H. The treatment of inclusion body myositis: a retrospective review and a randomized, prospective trial of immunosuppressive therapy. Medicine 72, 225–235 (1993).
doi: 10.1097/00005792-199307000-00002
Soueidan, S. A. & Dalakas, M. C. Treatment of inclusion-body myositis with high-dose intravenous immunoglobulin. Neurology 43, 876–879 (1993).
doi: 10.1212/WNL.43.5.876
Amato, A. A. et al. Inclusion body myositis: treatment with intravenous immunoglobulin. Neurology 44, 1516–1518 (1994).
doi: 10.1212/WNL.44.8.1516
Barohn, R. J., Amato, A. A., Sahenk, Z., Kissel, J. T. & Mendell, J. R. Inclusion body myositis: explanation for poor response to immunosuppressive therapy. Neurology 45, 1302–1304 (1995).
doi: 10.1212/WNL.45.7.1302
Barohn, R. J. et al. Pilot trial of etanercept in the treatment of inclusion-body myositis. Neurology 66, S123–S124 (2006).
doi: 10.1212/01.wnl.0000192258.32408.54
Kosmidis, M. L., Alexopoulos, H., Tzioufas, A. G. & Dalakas, M. C. The effect of anakinra, an IL1 receptor antagonist, in patients with sporadic inclusion body myositis (sIBM): a small pilot study. J. Neurol. Sci. 334, 123–125 (2013).
doi: 10.1016/j.jns.2013.08.007
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT00079768 (2010).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT00917956 (2010).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT01519349 (2017).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT02483845 (2017).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT02250443 (2018).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT00802815 (2014).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT00769860 (2017).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT01423110 (2017).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT01925209 (2017).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT02481453 (2019).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT02753530 (2018).