Anti-PM-Scl antibodies in a patient with inclusion body myositis

A. Selva-O'Callaghan1,, T. Mijares-Boeckh-Behrens1, M. Labrador-Horrillos2, R. Solans-Laque1, J. Ma Grau-Junyent3 and M. Vilardell-Tarres1

1 Internal Medicine Department,
2 Autoimmunity Research Unit, Vall d'Hebron General Hospital and
3 Grup d'Investigació Muscular, Hospital Clínic Provincial, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

SIR, The term inclusion body myositis (IBM) was coined in 1971 by Yunis and Samaha [1] to describe a subset of patients with refractory chronic myositis whose muscle biopsies showed, in addition to inflammation, abnormal muscle fibers containing vacuoles and characteristic filamentous inclusions in the cytoplasm and nuclei. A sporadic and a hereditary form have been recognized [2]. The cause of sporadic IBM is not known and it is considered an idiopathic inflammatory myopathy together with polymyositis and dermatomyositis. In the latter two diseases a number of autoantibodies have been detected, some of them being specific of myositis (anti-Jo-1, other antisynthetases and anti-Mi-2) and others associated with myositis, occurring also in other related conditions (anti-PM-Scl, anti-U1RNP). It has recently been suggested that myositis-specific or myositis-associated autoantibodies do not occur in IBM [3]. We describe the case of a patient with IBM and anti-PM-Scl autoantibodies.

A 36-yr-old woman presented with a history of progressive, proximal, symmetrical muscle weakness of the limb girdles and the neck. Physical examination showed asymmetric proximal and distal muscle weakness of arms and legs. An objective determination of strength assessed by MRC scale showed: neck flexors 3, right and left triceps 3, right iliopsoas 4, right quadriceps 3 and left quadriceps 2.5, right and left anterior tibial 3, left gastrocnemius 4, and all other muscles 5. The patient did not complain of arthralgias, Raynaud's phenomenon, skin changes or dysphagia. Laboratory analysis showed elevated serum creatinine phosphokinase (243 IU/l; normal value<195 IU/l). Fibrillation potentials with positive sharp waves and a mixed pattern of short duration/small-amplitude motor unit potentials, with several long duration high-amplitude motor unit potentials in proximal and distal muscles, were found on electromyogram. A muscle biopsy of left gastrocnemius revealed endomysial inflammatory infiltrates and the presence of rimmed vacuoles characteristic of IBM (Fig. 1Go). Antinuclear antibodies were positive (1/640 in a nucleolar and nucleoplasmic pattern) and anti-PM-Scl antibodies were found by immunoprecipitation from [35S]methionine-labelled HeLa cell extracts (Fig. 2Go). Wide-angle microscopy of nailfolds showed unspecific changes of the capillary bed, without loss of capillaries, and a few enlarged nailfold capillary loops. Treatment with corticosteroids was instituted without significant clinical response. Muscle strength deteriorated progressively during the following 5-yr period, with little subjective improvement after treatment with azathioprine and intravenous immunoglobulin. No features of systemic sclerosis were observed during follow up in this time period.



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FIG. 1. Muscle biopsy tissue, showing marked variability in fibre size with mild endomisial inflammatory infiltrate together with numerous rimmed vacuoles (black arrow) in some muscle fibres. Modified Gomori's trichrome in frozen tissue x182.

 


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FIG. 2. Autoradiogram of a 12.5% polyacrylamide gel fractionation of [35S]methionine-labelled proteins present in protein A–Sepharose-facilitated immunoprecipitates from a total HeLa cell extract, using five serum samples from patients with anti-PM-Scl. These antisera immunoprecipitate the characteristic protein complex of PM-Scl with molecular weight of 20–110 kDa (a–g). Lane 4 contains anti-PM-Scl of the IBM patient. C+ contains anti-PM-Scl reference serum. shn, normal human serum; MW, molecular weight.

 
IBM is an inflammatory myopathy that occurs most frequently in patients older than 50 yr, with a male predominance. Some histological features resemble polymyositis, but the finding of vacuoles within muscle fibres, its chronic, progressive and refractory clinical course, and the lack of immunological abnormalities in blood differentiate IBM from this disease. IBM has been found associated with other autoimmune diseases in some cases [4] and one report also suggests the rare occurrence (3%) of anti-Jo-1 antibodies [5]. Others did not find anti-Jo-1 or other myositis-specific or myositis associated antibodies in IBM [3, 6, 7]. In a single case, positivity to anti-Jo-1 antibodies seems to confer a marked and sustained clinical improvement after oral prednisone treatment, favouring the hypothesis that the presence of myositis-specific autoantibodies (MSA) in patients with IBM is the result of an identical immunological mechanism as in MSA-positive patients with dermatomyositis or polymyositis [8]. Nevertheless, in the case presented here the presence of a myositis-associated autoantibody does not confer a good prognosis to the patient.

Inflammatory myopathies are characterized by distinctive autoantibodies that are associated with certain clinical features and immunogenetic patterns. The anti-PM-Scl autoantibody is directed against a multi-subunit nucleolar and nucleolar protein complex. It has been found in patients with myositis, scleroderma and the polymyositis–scleroderma overlap syndrome, which combines myositis, Raynaud's phenomenon, arthritis and interstitial lung disease, but not in IBM patients [9, 10]. This patient did not have any features of scleroderma except for the unspecific nailfold capillary bed changes that could be related tothe presence of the autoantibody. To our knowledge the association of IBM and anti-PM-Scl antibodies has not been described previously. This case adds some evidence to the possible autoimmune basis in patients with IBM.

Notes

Correspondence to: A. Selva-O'Callaghan, C/Siracusa No.12 BIS ‘A’, Barcelona 08012, Spain. E-mail: aselva{at}hg.vhebron.es Back

References

  1. Yunis J, Samaha F. Inclusion body myositis. Lab Invest 1971;25:240–8.[ISI][Medline]
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  3. Targoff IN. Update on myositis-specific and myositis associated autoantibodies. Curr Opin Rheumatol 2000;12:475–81.[CrossRef][ISI][Medline]
  4. Mikol J, Engel AG. Inclusion body myositis. In: Engel AG, Franzini-Armstrong C, eds. Myology, Vol. II. New York: McGraw Hill, 1994:1384–98.
  5. Koffman BM, Rugiero M, Dalakas MC. Immune-mediated conditions and antibodies associated with sporadic inclusion body myositis. Muscle Nerve 1998;21:115–7.[CrossRef][ISI][Medline]
  6. Hengstman GJ, van Engelen BG, Badrising UA, van den Hoogen FHJ, van Venrooij WJ. Presence of anti-Jo-1 autoantibody excludes inclusion body myositis. Ann Neurol 1998;44:423.[ISI][Medline]
  7. Love LA, Leff RL, Fraser DD et al. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore) 1991;70:360–74.[ISI][Medline]
  8. Hengstman GJD, Ter Laak HJ, Van Engelen BGM, Van Venrooij WJ. Anti-Jo-1 positive inclusion body myositis with a marked and sustained clinical improvement after oral prednisone. J Neurol Neurosurg Psychiatry 2001;70:706.[Free Full Text]
  9. Ioannou Y, Sultan S, Isenberg DA. Myositis overlap syndromes. Curr Opin Rheumatol 1999;11:468–74.[CrossRef][Medline]
  10. Jablonska S, Blaszczyk M. Scleromyositis: a scleroderma/polymyositis overlap syndrome. Clin Rheumatol 1998;17:525–32.
Accepted 19 December 2002





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