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BMC Cardiovascular Disorders

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Open Access 01-12-2021 | Diseases of the neuromuscular synapses and muscles | Case report

Immunotherapy reversed myopathy but not cardiomyopathy in a necrotizing autoimmune myopathy patient with positive anti-SRP and MDA-5 autoantibodies

Authors: Xue Ma, Li Xu, Yue Li, Bitao Bu

Published in: BMC Cardiovascular Disorders | Issue 1/2021

Abstract

Background

Necrotizing autoimmune myopathy (NAM) is pathologically characterized by myofiber necrosis and regeneration with paucity or absence of inflammatory cells in muscle biopsy. Two autoantibodies, namely anti-signal recognition particle (SRP)-antibodies and anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)-antibodies, are typically specific with NAM. Anti-SRP-positive NAM can be associated with cardiomyopathy which responds well to immunotherapy. Here we reported an anti-SRP-antibody and anti-MDA5-antibody NAM patient who developed severe cardiomyopathy after gaining significant improvement of myopathy and subsequently accepted heart transplantation.

Case presentation

A NAM case with both positive anti-SRP and MDA-5 antibodies who gained significant improvement of the skeletal muscle weakness with immunotherapy, but 3 years later he developed severe dilated cardiomyopathy and at last received heart transplantation. Myocardial biopsy showed disarranged and atrophic myofibers, remarkable interstitial fibrosis without inflammatory infiltrates. Immunohistochemistry analysis revealed increased polyubiquitin-binding protein p62/SQSTM1 protein expression and the positive staining of cleaved-caspase 3 in a few cardiomyocytes. After the transplantation, the patient was symptom-free on oral prednisone (10 mg/day) and tacrolimus (2 mg/day).

Conclusions

We described the first case of anti-SRP and anti-MAD5 positive NAM who had received heart transplantation because of cardiopathy. Though the myopathy had been clinically improved after immunotherapy, the cardiomyopathy remained progressive and lethal. The processes of dysfunctional autophagy and augmented apoptosis were putatively pathophysiological mechanisms underlying cardiac damage in anti-SRP and anti-MAD5 positive NAM.

Day JA, Limaye V. Immune-mediated necrotising myopathy: a critical review of current concepts. Semin Arthritis Rheum. 2019. https://doi.org/10.1016/j.semarthrit.2019.04.002.CrossRefPubMed

Anquetil C, Boyer O, Wesner N, Benveniste O, Allenbach Y. Myositis-specific autoantibodies, a cornerstone in immune-mediated necrotizing myopathy. Autoimmun Rev. 2019;18(3):223–30. https://doi.org/10.1016/j.autrev.2018.09.008.CrossRefPubMed

Romisch K, Ribes V, High S, Lutcke H, Tollervey D, Dobberstein B. Structure and function of signal recognition particle (SRP). Mol Biol Rep. 1990;14(2–3):71–2. https://doi.org/10.1007/BF00986769.CrossRefPubMed

Reeves WH, Nigam SK, Blobel G. Human autoantibodies reactive with the signal-recognition particle. Proc Natl Acad Sci USA. 1986;83(24):9507–11. https://doi.org/10.1073/pnas.83.24.9507.CrossRefPubMedPubMedCentral

Bergua C, Chiavelli H, Allenbach Y, Arouche-Delaperche L, Arnoult C, Bourdenet G, et al. In vivo pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy. Ann Rheum Dis. 2019;78(1):131–9. https://doi.org/10.1136/annrheumdis-2018-213518.CrossRefPubMed

Gupta R, Wayangankar SA, Targoff IN, Hennebry TA. Clinical cardiac involvement in idiopathic inflammatory myopathies: a systematic review. Int J Cardiol. 2011;148(3):261–70. https://doi.org/10.1016/j.ijcard.2010.08.013.CrossRefPubMed

Khoo T, Stokes MB, Teo K, Proudman S, Basnayake S, Sanders P, et al. Cardiac involvement in idiopathic inflammatory myopathies detected by cardiac magnetic resonance imaging. Clin Rheumatol. 2019;38(12):3471–6. https://doi.org/10.1007/s10067-019-04678-z.CrossRefPubMed

Thiebaut M, Terrier B, Menacer S, Berezne A, Bussone G, Goulvestre C, et al. Antisignal recognition particle antibodies-related cardiomyopathy. Circulation. 2013;127(5):e434–6. https://doi.org/10.1161/CIRCULATIONAHA.112.118877.CrossRefPubMed

Hara A, Amano R, Yokote H, Ijima M, Zeniya S, Uchihara T, et al. Secondary cardiac involvement in anti-SRP-antibody-positive myopathy: an 87-year-old woman with heart failure symptoms as the first clinical presentation. BMC Neurol. 2020;20(1):29. https://doi.org/10.1186/s12883-020-1599-5.CrossRefPubMedPubMedCentral

10.

Takeguchi-Kikuchi S, Hayasaka T, Katayama T, Kano K, Takahashi K, Saito T, et al. Anti-signal recognition particle antibody-positive necrotizing myopathy with secondary cardiomyopathy: the first myocardial biopsy- and multimodal imaging-proven case. Intern Med. 2019. https://doi.org/10.2169/internalmedicine.2564-18.CrossRefPubMedPubMedCentral

11.

Betteridge Z, Tansley S, Shaddick G, Chinoy H, Cooper RG, New RP, et al. Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients. J Autoimmun. 2019;101:48–55. https://doi.org/10.1016/j.jaut.2019.04.001.CrossRefPubMedPubMedCentral

12.

Ortiz-Santamaria V, Babot A, Ferrer C. Anti-MDA5-positive dermatomyositis: an emerging entity with a variable clinical presentation. Scand J Rheumatol. 2017;46(6):509–11. https://doi.org/10.1080/03009742.2017.1340512.CrossRefPubMed

13.

Pau-Charles I, Moreno PJ, Ortiz-Ibanez K, Lucero MC, Garcia-Herrera A, Espinosa G, et al. Anti-MDA5 positive clinically amyopathic dermatomyositis presenting with severe cardiomyopathy. J Eur Acad Dermatol Venereol. 2014;28(8):1097–102. https://doi.org/10.1111/jdv.12300.CrossRefPubMed

14.

Kassardjian CD, Lennon VA, Alfugham NB, Mahler M, Milone M. Clinical features and treatment outcomes of necrotizing autoimmune myopathy. Jama Neurol. 2015;72(9):996–1003. https://doi.org/10.1001/jamaneurol.2015.1207.CrossRefPubMed

15.

Danko K, Ponyi A, Constantin T, Borgulya G, Szegedi G. Long-term survival of patients with idiopathic inflammatory myopathies according to clinical features—a longitudinal study of 162 cases. Medicine. 2004;83(1):35–42. https://doi.org/10.1097/01.md.0000109755.65914.5e.CrossRefPubMed

16.

Targoff IN, Johnson AE, Miller FW. Antibody to signal recognition particle in polymyositis. Arthritis Rheum. 1990;33(9):1361–70. https://doi.org/10.1002/art.1780330908.CrossRefPubMed

17.

Hengstman GJ, ter Laak HJ, Vree Egberts WT, Lundberg IE, Moutsopoulos HM, Vencovsky J, et al. Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy. Ann Rheum Dis. 2006;65(12):1635–8. https://doi.org/10.1136/ard.2006.052191.CrossRefPubMedPubMedCentral

18.

Li JM, Horsfall AC, Maini RN. Anti-La (SS-B) but not anti-Ro52 (SS-A) antibodies cross-react with laminin—a role in the pathogenesis of congenital heart block? Clin Exp Immunol. 1995;99(3):316–24. https://doi.org/10.1111/j.1365-2249.1995.tb05552.x.CrossRefPubMedPubMedCentral

19.

Ambrosi A, Dzikaite V, Park J, Strandberg L, Kuchroo VK, Herlenius E, et al. Anti-Ro52 monoclonal antibodies specific for amino acid 200–239, but not other Ro52 epitopes, induce congenital heart block in a rat model. Ann Rheum Dis. 2012;71(3):448–54. https://doi.org/10.1136/annrheumdis-2011-200414.CrossRefPubMed

20.

Li W, Yang Q, Mao Z. Signaling and induction of chaperone-mediated autophagy by the endoplasmic reticulum under stress conditions. Autophagy. 2018;14(6):1094–6. https://doi.org/10.1080/15548627.2018.1444314.CrossRefPubMedPubMedCentral

21.

Girolamo F, Lia A, Annese T, Giannini M, Amati A, D’Abbicco D, et al. Autophagy markers LC3 and p62 accumulate in immune-mediated necrotizing myopathy. Muscle Nerve. 2019. https://doi.org/10.1002/mus.26608.CrossRefPubMed

22.

Fischer N, Preusse C, Radke J, Pehl D, Allenbach Y, Schneider U, et al. Sequestosome-1 (p62) expression reveals chaperone-assisted selective autophagy in immune-mediated necrotizing myopathies. Brain Pathol. 2019. https://doi.org/10.1111/bpa.12772.CrossRefPubMedPubMedCentral

23.

Giannini M, Girolamo F, Lia A, Amati A, Serlenga L, Abbicco D, et al. Autophagy marker LC3 accumulates in immune-mediated necrotizing myopathy muscle fibres. Arthritis Rheumatol. 2018. https://doi.org/10.1002/mus.26608.CrossRefPubMedPubMedCentral

24.

Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8(9):741–52. https://doi.org/10.1038/nrm2239.CrossRefPubMed

25.

Charge SBP, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiol Rev. 2004;84(1):209–38. https://doi.org/10.1152/physrev.00019.2003.CrossRefPubMed

26.

Tidball JG. Regulation of muscle growth and regeneration by the immune system. Nat Rev Immunol. 2017;17(3):165–78. https://doi.org/10.1038/nri.2016.150.CrossRefPubMedPubMedCentral

27.

Hashimoto H, Olson EN, Bassel-Duby R. Therapeutic approaches for cardiac regeneration and repair. Nat Rev Cardiol. 2018;15(10):585–600. https://doi.org/10.1038/s41569-018-0036-6.CrossRefPubMedPubMedCentral

28.

van Berlo JH, Molkentin JD. An emerging consensus on cardiac regeneration. Nat Med. 2014;20(12):1386–93. https://doi.org/10.1038/nm.3764.CrossRefPubMedPubMedCentral

Title: Immunotherapy reversed myopathy but not cardiomyopathy in a necrotizing autoimmune myopathy patient with positive anti-SRP and MDA-5 autoantibodies
Authors: Xue Ma
Li Xu
Yue Li
Bitao Bu
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Diseases of the neuromuscular synapses and muscles
Cardiomyopathy
Heart Transplantation
Heart Transplantation
Heart Transplantation
Heart Transplantation
Heart Transplantation
Myopathy
Tacrolimus
Published in: BMC Cardiovascular Disorders / Issue 1/2021
Electronic ISSN: 1471-2261
DOI: https://doi.org/10.1186/s12872-021-01900-2

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Conclusions

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