Inflammatory myopathy with anti-signal recognition particle antibodies: case series of 100 patients

Abstract

Background: Anti-signal recognition particle (SRP) antibodies are used as serological markers of necrotizing myopathy, which is characterized by many necrotic and regenerative muscle fibers without or with minimal inflammatory cell infiltration. The clinical spectrum associated with anti-SRP antibodies seems to be broad.

Objective: To describe the clinical characteristics, autoantibodies status, and neurological outcome associated with anti-SRP antibody.

Methods: We studied clinical and laboratory findings of 100 patients with inflammatory myopathy and anti-SRP antibodies. Anti-SRP antibodies in serum were detected by the presence of 7S RNA using RNA immunoprecipitation. In addition, enzyme-linked immunosorbent assays (ELISAs) using a 54-kD protein of SRP (SRP54) and 3-hydroxyl-3-methylglutatyl-coenzyme A reductase (HMGCR) were also conducted.

Results: The mean onset age of the 61 female and 39 male patients was 51 years (range 4-82 years); duration ≥ 12 months before diagnosis was seen in 23 cases. All patients presented limbs weakness; 63 had severe weakness, 70 neck weakness, 41 dysphagia, and 66 muscle atrophy. Extramuscular symptoms and associated disorders were infrequent. Creatine kinase levels were mostly more than 1000 IU/L. Histological diagnosis showed 84 patients had necrotizing myopathy, and apparent cell infiltration was observed in 16 patients. Anti-SRP54 antibodies were undetectable in 18 serum samples with autoantibodies to 7S RNA. Anti-HMGCR antibodies were positive in 3 patients without the statin treatment, however, were negative in 5 patients with statin-exposure at disease onset. All but 3 patients were treated by corticosteroids and 62 (77 %) of these 81 patients required additional immunotherapy. After 2-years treatment, 22 (27 %) of these 81 patients had poor neurological outcomes with modified Rankin scale scores of 3-5. Multivariate analysis revealed that pediatric disease onset was associated with the poor outcomes.

Conclusion: Anti-SRP antibodies are associated with different clinical courses and histological presentations.

Fig. 1

RNA immunoprecipitation assay. Urea and 8 % PAGE of phenol-extracted immunoprecipitation from HeLa cell extracts were developed with silver staining. Total RNA indicates 7S RNA and transfer RNA regions. The serum samples #2 and #6 contained anti-signal recognition particle (SRP) antibodies. In contrast, one of autoantibodies against aminoacyl transfer RNA synthetase, anti-PL-7 antibody (anti-threonyl-tRNA synthetase) was found in serum #5

Fig. 2

Distribution of onset ages in the 100 patients with inflammatory myopathy with anti- SRP antibody

Fig. 3

Muscle images of thighs in patients with anti-SRP antibodies. (a) Muscle atrophy on MRI T1 images. (b) High signal intensity on MRI STIR images. (c) Increased signals on MRI STIR images (upper) and muscle atrophy in CT (lower)

Fig. 4

SRP54 enzyme-linked immunosorbent assay (ELISA). (a) Antibodies reactive with recombinant SRP54 protein by ELISA in sera from patients with anti-7S RNA positive myopathy, myositis without autoantibodies, myasthenia gravis, muscular dystrophy, and healthy controls. The cut-off level for positivity of anti-SRP54 antibody index is indicated by the broken line. (b) Serial changes of anti-SRP54 antibody index between pre- and post-treatment in 10 patients with anti-SRP antibodies. (c) Correlation of anti-SRP54 antibody index determined by ELISA and serum creatine kinase in 100 patients with anti-SRP antibodies