Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2002 Oct;73(4):420–428. doi: 10.1136/jnnp.73.4.420

Myopathy with antibodies to the signal recognition particle: clinical and pathological features

T Miller 1, M Al-Lozi 1, G Lopate 1, A Pestronk 1
PMCID: PMC1738058  PMID: 12235311

Abstract

Objectives: To study myopathies with serum antibodies to the signal recognition particle (SRP), an unusual, myositis specific antibody associated syndrome that has not been well characterised pathologically.

Methods: Clinical, laboratory, and myopathological features were evaluated in seven consecutive patients with a myopathy and serum anti-SRP antibodies, identified over three years. The anti-SRP myopathy was compared with myopathology in other types of inflammatory and immune myopathies.

Results: The patients with anti-SRP antibodies developed weakness at ages ranging from 32 to 70 years. Onset was seasonal (August to January). Weakness became severe and disability developed rapidly over a period of months. Muscle pain and fatigue were present in some patients. No patient had a dermatomyositis-like rash. Serum creatine kinase was very high (3000 to 25 000 IU/l). Muscle biopsies showed an active myopathy, including muscle fibre necrosis and regeneration. There was prominent endomysial fibrosis, but little or no inflammation. Endomysial capillaries were enlarged, reduced in number, and associated with deposits of the terminal components of complement (C5b-9, membrane attack complex). Strength improved in several patients after corticosteroid treatment.

Conclusions: Myopathies associated with anti-SRP antibodies may produce severe and rapidly progressive weakness and disability. Muscle biopsies show active myopathy with pathological changes in endomysial capillaries but little inflammation. Corticosteroid treatment early in the course of the illness is often followed by improvement in strength. In patients with rapidly progressive myopathies and a high serum creatine kinase but little inflammation on muscle biopsy, measurement of anti-SRP antibodies and pathological examination of muscle, including evaluation of endomysial capillaries, may provide useful information on diagnosis and treatment.

Full Text

The Full Text of this article is available as a PDF (263.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arahata K., Engel A. G. Monoclonal antibody analysis of mononuclear cells in myopathies. IV: Cell-mediated cytotoxicity and muscle fiber necrosis. Ann Neurol. 1988 Feb;23(2):168–173. doi: 10.1002/ana.410230210. [DOI] [PubMed] [Google Scholar]
  2. Blobe G. C., Schiemann W. P., Lodish H. F. Role of transforming growth factor beta in human disease. N Engl J Med. 2000 May 4;342(18):1350–1358. doi: 10.1056/NEJM200005043421807. [DOI] [PubMed] [Google Scholar]
  3. Blume G., Pestronk A., Frank B., Johns D. R. Polymyositis with cytochrome oxidase negative muscle fibres. Early quadriceps weakness and poor response to immunosuppressive therapy. Brain. 1997 Jan;120(Pt 1):39–45. doi: 10.1093/brain/120.1.39. [DOI] [PubMed] [Google Scholar]
  4. Bohan A., Peter J. B., Bowman R. L., Pearson C. M. Computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine (Baltimore) 1977 Jul;56(4):255–286. doi: 10.1097/00005792-197707000-00001. [DOI] [PubMed] [Google Scholar]
  5. Brouwer R., Hengstman G. J., Vree Egberts W., Ehrfeld H., Bozic B., Ghirardello A., Grøndal G., Hietarinta M., Isenberg D., Kalden J. R. Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis. 2001 Feb;60(2):116–123. doi: 10.1136/ard.60.2.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chizzolini Carlo, Raschi Elena, Rezzonico Roger, Testoni Cinzia, Mallone Roberto, Gabrielli Armando, Facchini Andrea, Del Papa Nicoletta, Borghi Maria Orietta, Dayer Jean Michel. Autoantibodies to fibroblasts induce a proadhesive and proinflammatory fibroblast phenotype in patients with systemic sclerosis. Arthritis Rheum. 2002 Jun;46(6):1602–1613. doi: 10.1002/art.10361. [DOI] [PubMed] [Google Scholar]
  7. Dalakas M. C. Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med. 1991 Nov 21;325(21):1487–1498. doi: 10.1056/NEJM199111213252107. [DOI] [PubMed] [Google Scholar]
  8. Emslie-Smith A. M., Engel A. G. Microvascular changes in early and advanced dermatomyositis: a quantitative study. Ann Neurol. 1990 Apr;27(4):343–356. doi: 10.1002/ana.410270402. [DOI] [PubMed] [Google Scholar]
  9. 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. 1991 Jun;41(6):936–939. doi: 10.1212/wnl.41.6.936. [DOI] [PubMed] [Google Scholar]
  10. Englund P., Lindroos E., Nennesmo I., Klareskog L., Lundberg I. E. Skeletal muscle fibers express major histocompatibility complex class II antigens independently of inflammatory infiltrates in inflammatory myopathies. Am J Pathol. 2001 Oct;159(4):1263–1273. doi: 10.1016/S0002-9440(10)62513-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grosshans H., Deinert K., Hurt E., Simos G. Biogenesis of the signal recognition particle (SRP) involves import of SRP proteins into the nucleolus, assembly with the SRP-RNA, and Xpo1p-mediated export. J Cell Biol. 2001 May 14;153(4):745–762. doi: 10.1083/jcb.153.4.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hilton-Jones D. Inflammatory muscle diseases. Curr Opin Neurol. 2001 Oct;14(5):591–596. doi: 10.1097/00019052-200110000-00007. [DOI] [PubMed] [Google Scholar]
  13. Keenan R. J., Freymann D. M., Stroud R. M., Walter P. The signal recognition particle. Annu Rev Biochem. 2001;70:755–775. doi: 10.1146/annurev.biochem.70.1.755. [DOI] [PubMed] [Google Scholar]
  14. Kissel J. T., Halterman R. K., Rammohan K. W., Mendell J. R. The relationship of complement-mediated microvasculopathy to the histologic features and clinical duration of disease in dermatomyositis. Arch Neurol. 1991 Jan;48(1):26–30. doi: 10.1001/archneur.1991.00530130034016. [DOI] [PubMed] [Google Scholar]
  15. Levin M. I., Mozaffar T., Al-Lozi M. T., Pestronk A. Paraneoplastic necrotizing myopathy: clinical and pathological features. Neurology. 1998 Mar;50(3):764–767. doi: 10.1212/wnl.50.3.764. [DOI] [PubMed] [Google Scholar]
  16. Mozaffar T., Pestronk A. Myopathy with anti-Jo-1 antibodies: pathology in perimysium and neighbouring muscle fibres. J Neurol Neurosurg Psychiatry. 2000 Apr;68(4):472–478. doi: 10.1136/jnnp.68.4.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Oldfors A., Fyhr I. M. Inclusion body myositis: genetic factors, aberrant protein expression, and autoimmunity. Curr Opin Rheumatol. 2001 Nov;13(6):469–475. doi: 10.1097/00002281-200111000-00003. [DOI] [PubMed] [Google Scholar]
  18. Pestronk A., Lopate G., Kornberg A. J., Elliott J. L., Blume G., Yee W. C., Goodnough L. T. Distal lower motor neuron syndrome with high-titer serum IgM anti-GM1 antibodies: improvement following immunotherapy with monthly plasma exchange and intravenous cyclophosphamide. Neurology. 1994 Nov;44(11):2027–2031. doi: 10.1212/wnl.44.11.2028. [DOI] [PubMed] [Google Scholar]
  19. Posner J. B. Anti-Hu autoantibody associated sensory neuropathy/encephalomyelitis: a model of paraneoplastic syndrome. Perspect Biol Med. 1995 Winter;38(2):167–181. doi: 10.1353/pbm.1995.0043. [DOI] [PubMed] [Google Scholar]
  20. Ringel S. P., Carry M. R., Aguilera A. J., Starcevich J. M. Quantitative histopathology of the inflammatory myopathies. Arch Neurol. 1986 Oct;43(10):1004–1009. doi: 10.1001/archneur.1986.00520100026010. [DOI] [PubMed] [Google Scholar]
  21. Schmidt W. A., Wetzel W., Friedländer R., Lange R., Sörensen H. F., Lichey H. J., Genth E., Mierau R., Gromnica-Ihle E. Clinical and serological aspects of patients with anti-Jo-1 antibodies--an evolving spectrum of disease manifestations. Clin Rheumatol. 2000;19(5):371–377. doi: 10.1007/s100670070030. [DOI] [PubMed] [Google Scholar]
  22. Targoff I. N., Johnson A. E., Miller F. W. Antibody to signal recognition particle in polymyositis. Arthritis Rheum. 1990 Sep;33(9):1361–1370. doi: 10.1002/art.1780330908. [DOI] [PubMed] [Google Scholar]
  23. Targoff I. N., Miller F. W., Medsger T. A., Jr, Oddis C. V. Classification criteria for the idiopathic inflammatory myopathies. Curr Opin Rheumatol. 1997 Nov;9(6):527–535. doi: 10.1097/00002281-199711000-00008. [DOI] [PubMed] [Google Scholar]
  24. Targoff I. N. Update on myositis-specific and myositis-associated autoantibodies. Curr Opin Rheumatol. 2000 Nov;12(6):475–481. doi: 10.1097/00002281-200011000-00001. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES