Anti‐signal recognition particle autoantibodies: marker of a necrotising myopathy
Department of Neurology, Neuromuscular Centre Nijmegen, University Medical Centre Nijmegen, PO Box 9101, Internal Code 935, 6500 HB Nijmegen, The Netherlands; g.hengstman@neuro.umcn.nl
Department of Neurology, Neuromuscular Centre Nijmegen, University Medical Centre Nijmegen, PO Box 9101, Internal Code 935, 6500 HB Nijmegen, The Netherlands; g.hengstman@neuro.umcn.nl
Abstract
Objective
To elucidate the clinical importance of the anti‐signal recognition particle (SRP) autoantibody in patients with myositis.
Methods
Retrospective systematic assessment of the clinical, laboratory and histological characteristics of 23 anti‐SRP‐positive patients from six European centres. Data were compared with a large group of anti‐SRP‐negative patients with myositis published previously.
Results
Clinically, patients with anti‐SRP autoantibodies often had a severe symmetric proximal muscle weakness resulting in marked disability, dysphagia and highly elevated levels of serum creatine kinase. Three patients had typical dermatomyositis rashes. The disease was associated with the occurrence of extramuscular signs and symptoms including interstitial lung disease. No association was found with an increased risk of cardiac involvement, and the disease carried a reasonably favourable prognosis with most patients responding to treatment. None of the patients had the typical histological features of myositis. Most muscle biopsy specimens showed the presence of necrotic muscle fibres and no inflammatory infiltrates.
Conclusions
Anti‐SRP autoantibodies are associated with a syndrome of a necrotising myopathy in the spectrum of immune‐mediated myopathies that differs from typical polymyositis. Further studies are needed to elucidate the pathogenesis and to clarify the role of the anti‐SRP autoantibodies in this unique disease.
Defined autoantibodies are detected in about 50% of patients with myositis and are traditionally divided into myositis‐specific autoantibodies and myositis‐associated autoantibodies, the myositis‐associated autoantibodies also occurring in autoimmune diseases without the presence of myositis.1 One of the myositis‐specific autoantibodies is the anti‐signal recognition particle (SRP) autoantibody, which is directed against components of the signal recognition particle.2
Earlier studies suggested an association between anti‐SRP autoantibodies and the presence of an acute and severe form of polymyositis with cardiac involvement, a poor response to immunosuppressive treatment and an increased mortality.3456 Others confirmed the presence of a relatively aggressive disease, but cardiac involvement was not found.7 In a recent study, Miller et al8 described the clinical and pathological features of seven patients with anti‐SRP autoantibodies. They concluded that anti‐SRP is associated with an immune‐mediated necrotising myopathy and not with polymyositis, characterised by a rapidly progressive severe proximal muscle weakness with an incomplete response to corticosteroids and no clinical signs or symptoms suggestive of multiorgan involvement. Furthermore, they found a predilection for the disease to start in the autumn. Kao et al9 were unable to confirm several of Miller's observations. In contrast with Miller et al,8 their patients did not have a large number of necrotic muscle fibres, nor was there a clear seasonal onset. Furthermore, they found multiorgan involvement in 25% of their patients.
To elucidate whether anti‐SRP is associated with a specific form of immune‐mediated myopathy, we analysed the clinical and histological data of the largest group of anti‐SRP‐positive patients to date in a systematic manner and compared this group with a large group of patients with myositis published previously.7
Acknowledgements
We thank Dr K Strub, University of Geneva, Switzerland for providing a 7SL cDNA/pSP64 construct. The work of GJDH was supported by NWO‐MW grant 940‐37‐009. The work is of WJvV and WTMVE were in part supported by the council for Chemical Sciences of The Netherlands Organization for Research (NWO‐CW), with financial aid from the Netherlands Technology Foundation (grant 349–3699). JV obtained institutional support MSM 0021620812 from the Ministry of Education, Youth and Sports.
Abbreviations
HLA - human leucocyte antigen
ILD - interstitial lung disease
MAC - membrane attack complex
SRP - signal recognition particle
Footnotes
Competing interests: None.
References
- 1. Brouwer R, Hengstman G J D, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A. et al Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis 200160116–123.
- 2. Reeves W H, Nigam S K, Blobel GHuman autoantibodies reactive with the signal‐recognition particle. Proc Natl Acad Sci USA 1986839507–9511. [Google Scholar]
- 3. Love L A, Leff R L, Fraser D D, Targoff I N, Dalakas M, Plotz P H, Miller F W. et al A new approach to the classification of idiopathic inflammatory myopathy: myositis‐specific autoantibodies define useful homogeneous groups. Medicine 199170360–374. [[PubMed]
- 4. Hausmanowa‐Petrusewicz I, Kowalska‐Olędzka E, Miller F W, Jarzabek C M, Targoff I N, Blaszczyk K M. et al Clinical, serologic, and immunogenetic features in Polish patients with idiopathic inflammatory myopathy. Arthritis Rheum 1997401257–1266. [[PubMed]
- 5. Hirakata M, Mimori T, Akizuki M, Craft J, Hardin J A, Homma MAutoantibodies to small nuclear and cytoplasmic ribonucleoproteins in Japanese patients with inflammatory muscle disease. Arthritis Rheum 199235449–456. [[PubMed][Google Scholar]
- 6. Targoff I N, Johnson A E, Miller F WAntibody to signal recognition particle in polymyositis. Arthritis Rheum 1990331361–1370. [[PubMed][Google Scholar]
- 7. Hengstman G J D, Brouwer R, Vree Egberts W T M. et al Clinical and serological characteristics of 125 Dutch myositis patients. Myositis specific autoantibodies aid in the differential diagnosis of the idiopathic inflammatory myopathies. J Neurol 200224969–75. [[PubMed]
- 8. Miller T, Al‐Lozi M T, Lopate G, Pestronk AMyopathy with antibodies to the signal recognition particle: clinical and pathological features. J Neurol Neurosurg Psychiatry 200273420–428. [Google Scholar]
- 9. Kao A H, Lacomis D, Lucas M, Fertig N, Oddis C VAnti‐signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy. Arthritis Rheum 200450209–215. [[PubMed][Google Scholar]
- 10. Phillips B A, Zilko P, Garlepp M J, Mastaglia F LFrequency of relapses in patients with polymyositis and dermatomyositis. Muscle Nerve 1998211668–1672. [[PubMed][Google Scholar]
- 11. Hirakata M, Nagai SInterstitial lung disease in polymyositis and dermatomyositis. Curr Opin Rheumatol 200012501–508. [[PubMed][Google Scholar]
- 12. Stern R, Godbold J H, Chess Q, Kagen L JECG abnormalities in polymyositis. Arch Intern Med 19841442185–2189. [[PubMed][Google Scholar]
- 13. Dalakas M C, Hohlfeld RPolymyositis and dermatomyositis. Lancet 2003362971–982. [[PubMed][Google Scholar]
- 14. Van der Pas J, Hengstman G J D, Ter Laak H J, Van Engelen B G MDiagnostic value of MHC class I staining in idiopathic inflammatory myopathies. J Neurol Neurosurg Psychiatry 200475136–139. [Google Scholar]
- 15. Sieb J P, Gillessen TIatrogenic and toxic myopathies. Muscle Nerve 200327142–156. [[PubMed][Google Scholar]
- 16. Levin M I, Mozaffar T, Al‐Lozi M T, Pestronk AParaneoplastic necrotizing myopathy: clinical and pathological features. Neurology 199850764–767. [[PubMed][Google Scholar]
- 17. Emslie‐Smith A M, Engel A GNecrotizing myopathy with pipestem capillaries, microvascular deposition of the complement membrane attack complex (MAC), and minimal cellular infiltration. Neurology 199141936–939. [[PubMed][Google Scholar]
- 18. Authier F J, Kondo H, Ghnassia R T, Revuz J, Gherardi R KNecrotizing myopathy with pipestem capillaries and minimal cellular infiltration: a case associated with cutaneous signs of dermatomyositis. Neurology 1996461448–1451. [[PubMed][Google Scholar]