Anti- C N1A antibodies in South Australian patients with inclusion body myositis.

Only recently, with the identification of antibodies to a 43-kDa muscle autoantigen, subsequently identified as cytoplasmic 50-nucleotidase 1A (cN1A) in sera from patients with inclusion body myositis (IBM), has a role for B-cell autoimmunity in IBM been demonstrated. IgG antibodies to cN1A have> 90% specificity and 34%–70% sensitivity in IBM. Detection of all 3 isotypes (IgG, IgM, and IgA) by enzyme-linked immunoassay (ELISA) has increased sensitivity to 76%. Hence, these antibodies may be useful biomarkers for IBM. We determined the prevalence and serological associations of anti-cN1A in South Australian patients with a definitive histological diagnosis of IBM, made by accepted histological criteria. All 58 patients fulfilled the histopathological requirements, and 55 of 58 fulfilled the clinicopathological requirements of the European Neuromuscular Centre (ENMC) criteria, which have superior performance in IBM diagnosis compared with other diagnostic criteria. The clinical distribution of muscle involvement is shown in Table 1. Autoantibody production in inflammatory myopathies is at least partially genetically determined, and myositis-specific autoantibodies (MSA) and myositis-associated autoantibodies (MAA) are associated with DR3 and DR4 in South Australian patients with inflammatory myositis. Hence, we sought to further determine whether production of anticN1A is also determined by class II alleles. Antibodies to cN1A were detected by ELISA, as described elsewhere in 24 of 69 (34.8%) patients with IBM. Autoantibodies of the IgM isotype were the most frequent (n5 17), followed by IgG (n5 13) and IgA (n5 5). All 3 isotypes were present in 1 patient; 9 sera showed antibodies of 2 isotypes (IgM and IgA, n5 2; IgM and IgG, n5 5; IgA and IgG, n5 2). There was no gender difference between IBM patients with anti-cN1A (15 of 24 women) compared with those without antibodies (27 of 45 women). Although some MSA have been associated with malignancy, there was no difference in FIGURE 1. Pedigree of the family with a non-dystrophic myotonic syndrome and a new mutation in the CLCN1 gene. The following individuals had DNA analysis, either by complete CLCN1 sequencing (III-2), or by targeted sequencing of CLCN1 exon 9 (II-2, IV-1, and IV-2).White symbols: healthy; white symbols with ?: history of myotonia is unclear; gray symbols: clinically affected; square: man; circle: woman; arrow: proband; cross: deceased; asterisk: year of birth.