Anti‐signal recognition particle autoantibodies: marker of a necrotising myopathy

G Hengstman

H ter Laak

W Egberts

I Lundberg

G J D Hengstman, H J ter Laak, B G M van Engelen, Department of Neurology, Neuromuscular Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

W T M Vree Egberts, W J van Venrooij, Department of Biochemistry, Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands

I E Lundberg, Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden

H M Moutsopoulos, Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece

J Vencovsky, Institute of Rheumatology, Prague, Czech Republic

A Doria, Division of Rheumatology, University of Padova, Padova, Italy

M Mosca, Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy

Correspondence to: G J D Hengstman
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

G J D Hengstman, H J ter Laak, B G M van Engelen, Department of Neurology, Neuromuscular Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, The NetherlandsW T M Vree Egberts, W J van Venrooij, Department of Biochemistry, Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The NetherlandsI E Lundberg, Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, SwedenH M Moutsopoulos, Department of Pathophysiology, School of Medicine, National University of Athens, Athens, GreeceJ Vencovsky, Institute of Rheumatology, Prague, Czech RepublicA Doria, Division of Rheumatology, University of Padova, Padova, ItalyM Mosca, Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, ItalyCorrespondence to: G J D Hengstman
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

Accepted 2006 May 1.

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.

Abstract

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.

Acknowledgements

Abbreviations

HLA - human leucocyte antigen

ILD - interstitial lung disease

MAC - membrane attack complex

SRP - signal recognition particle

Abbreviations

Footnotes

Competing interests: None.

Footnotes

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