Polymyositis, Pulmonary Fibrosis and Autoantibodies to Aminoacyl-tRNA Synthetase Enzymes

Marguerie, Christopher; Bunn, Christopher; Beynon, H. L. C.; Bernstein, Robert; Hughes, Judith M.; So, Alex; Walport, Mark

doi:10.1093/qjmed/77.1.1019

Cited by 329 publications

(227 citation statements)

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“…There is a retrospective collaborative study in which chart reviews of patients whose sera were positive for anti-Jo-1 in 2 hospital laboratories over an 8-year period were conducted (16). Sera testing positive by counterimmunoelectrophoresis were further tested for anti-Jo-1 by immunoprecipitation and enzyme inhibition assays.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity and specificity of anti‐Jo‐1 antibodies in autoimmune diseases with myositis

Vázquez‐Abad

Rothfield

1996

Arthritis & Rheumatism

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Objective. To determine the sensitivity and specificity of anti-Jo-1 in systemic sclerosis (SSc) patients with and without myositis.Methods. Immunoblots on HeLa nuclei were used to screen sera from 554 consecutive connective tissue disease patients. Those who had 45-55-kd bands, all patients with polymyositis/derrnatomyositis (PM/DM), and a random selection of SSc, Raynaud's disease, systemic lupus erythematosus, and rheumatoid arthritis patients were also studied by anti-Jo-1 enzyme-linked immunosorbent assay and by immunoblots on rabbit pooled aminoacyl-transfer RNA synthetase.Results. Anti-Jo-1 was present only in 8 of the 40 PM/DM patients.Conclusion. Anti-Jo-1 is specific for PM/DM.Anti-Jo-1 antibodies are found in polymyositis/ dermatomyositis (PM/DM) patients, especially in those with lung involvement (1). Anti-Jo-1 is directed at histidyl-transfer RNA (tRNA) synthetase (Jo-1 autoantigen), which is a dimer of 50-kd subunits found in the cytoplasm (1,2). Anti-Jo-1 may be detected by double immunodiffusion, immunoblotting, and enzyme-linked immunosorbent assay (ELISA) (3) using an antigen containing Jo-1 and standard positive and negative control sera. The presence of anti-Jo-1 in systemic sclerosis (SSc) patients has not been examined in large-scale studies. SSc patients frequently present with lung involvement, and, in some cases, with myositis. Therefore, in the present study, we decided to screen our large series of consecutive SSc patients for the Submitted for publication July 25, 1995; accepted in revised form September 29, 1995. presence of anti-Jo-1 and compare them with other connective tissue disease patients with and without myositis.Our results show that anti-Jo-1 is present in 20.0% of PM/DM patients (8 of 40), and is absent from SSc patients' sera, including those with PM/DM overlap and those with elevated creatine phosphokinase (CPK) levels and muscle pain, but who do not fulfill criteria for PM/DM, with or without interstitial lung fibrosis. PATIENTS AND METHODSPatients and controls. All patients and controls were seen in the Rheumatology Clinics at

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Section: Discussionmentioning

confidence: 99%

Sensitivity and specificity of anti‐Jo‐1 antibodies in autoimmune diseases with myositis

Vázquez‐Abad

Rothfield

1996

Arthritis & Rheumatism

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“…(15,18,19), 10% had anti-La/SS-B antibodies (18,19), and 10% had anti-RNP antibodies (19). Moreover, anti-Ro/S-AA antibodies were detected most frequently in PM/DM patients with anti-ARS autoantibodies (20).…”

Section: T a B L E 1 Cl I N I C A L F E A T U R E S O F P A T I E Nmentioning

confidence: 99%

Clinical and Pathological Findings of Interstitial Lung Disease Patients with Anti-Aminoacyl-tRNA Synthetase Autoantibodies

et al. 2010

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Objective (range, 5-47 months) 5%) had ILD-preceding myositis, and 4 (50%) had simultaneous onset. Chest high-resolution computed tomography frequently showed lung-base predominant ground glass opacities (GGO) with volume loss. The results of surgical lung biopsies indicated that 4 patients had nonspecific interstitial pneumonia (NSIP) and/or organizing pneumonia (OP) patterns. All but 1 received corticosteroid therapy, and 6 patients were also given cyclosporin. The mean duration of follow-up was 22 months

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“…Initially thought to be a marker of inflammatory myopathy alone, anti-Jo-1 antibody is now associated with a distinct clinical entity known as the antisynthetase syndrome, which includes fever, myositis, interstitial lung disease (ILD), nonerosive arthropathy, mechanic's hands, and Raynaud's phenomenon (5). ILD is especially prevalent in the antisynthetase syndrome, occurring in ϳ75% of patients with anti-Jo-1 antibody compared to ϳ30% of patients with IIM in the absence of antisynthetase antibodies (6)(7)(8).…”

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confidence: 99%

“…Anti-Jo-1 antibody is one of several antisynthetase antibodies that have been described, each of which has been associated with overlapping features of the antisynthetase syndrome (5,9). Anti-Jo-1 antibody recognizes different epitopes of histidyl-tRNA synthetase (Jo-1), including the subunit that catalyzes binding between the amino acid histidine and its cognate tRNA in the process of protein synthesis (5,10,11).…”

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confidence: 99%

“…Anti-Jo-1 antibody recognizes different epitopes of histidyl-tRNA synthetase (Jo-1), including the subunit that catalyzes binding between the amino acid histidine and its cognate tRNA in the process of protein synthesis (5,10,11). Based on a range of immunologic and immunogenetic data, Jo-1 likely plays a direct role in the induction and maintenance of autoimmunity in the antisynthetase syndrome.…”

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Anti–Jo‐1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy

Stone¹,

Oddis²,

Fertig³

et al. 2007

Arthritis & Rheumatism

194

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Objective. Previous case series have examined the relationship between anti-Jo-1 antibody levels and myositis disease activity, demonstrating equivocal results. Using enzyme-linked immunosorbent assays (ELISAs) and novel measures of myositis disease activity, the current study was undertaken to systematically reexamine the association between anti-Jo-1 antibody levels and various disease manifestations of myositis.Methods. Serum anti-Jo-1 antibody levels were quantified using 2 independent ELISA methods, while disease activity was retrospectively graded using the Myositis Disease Activity Assessment Tool, which measures disease activity in 7 different organ systems via the Myositis Disease Activity Assessment Visual Analog Scale (VAS) and the Myositis Intention-to-Treat Index (MITAX) components. Spearman's rank correlation coefficients and mixed linear regression analysis were used to identify associations between anti-Jo-1 antibody levels and organ-specific disease activity in crosssectional and longitudinal analyses, respectively.Results. Cross-sectional assessment of 81 patients with anti-Jo-1 antibody revealed a modest correlation between the anti-Jo-1 antibody level and the serum creatine kinase (CK) level, as well as muscle and joint disease activity. Correlation coefficients were similar for CK levels (r s ‫؍‬ 0.38, P ‫؍‬ 0.002), myositis VAS (r s ‫؍‬ 0.36, P ‫؍‬ 0.002), and arthritis VAS (r s ‫؍‬ 0.40, P ‫؍‬ 0.001). In multiple regression analyses of 11 patients with serial samples, anti-Jo-1 antibody levels correlated significantly with CK levels (R 2 ‫؍‬ 0.65, P ‫؍‬ 0.0002), myositis VAS (R 2 ‫؍‬ 0.53, P ‫؍‬ 0.0008), arthritis VAS (R 2 ‫؍‬ 0.53, P ‫؍‬ 0.006), pulmonary VAS (R 2 ‫؍‬ 0.69, P ‫؍‬ 0.005), global VAS (R 2 ‫؍‬ 0.63, P ‫؍‬ 0.002), and global MITAX (R 2 ‫؍‬ 0.64, P ‫؍‬ 0.0003).Conclusion. In this large series of patients with idiopathic inflammatory myopathy, anti-Jo-1 antibody levels correlated modestly with muscle and joint disease, an association confirmed by a custom ELISA using recombinant human Jo-1. More striking associations emerged in a smaller longitudinal subset of patients that link anti-Jo-1 antibody levels to muscle, joint, lung, and global disease activity.

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Polymyositis, Pulmonary Fibrosis and Autoantibodies to Aminoacyl-tRNA Synthetase Enzymes

Cited by 329 publications

References 0 publications

Sensitivity and specificity of anti‐Jo‐1 antibodies in autoimmune diseases with myositis

Sensitivity and specificity of anti‐Jo‐1 antibodies in autoimmune diseases with myositis

Clinical and Pathological Findings of Interstitial Lung Disease Patients with Anti-Aminoacyl-tRNA Synthetase Autoantibodies

Anti–Jo‐1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy

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