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Arthritis und Rheuma 2015; 35(03): 176-182
DOI: 10.1055/s-0037-1618370
Kinder-rheumatologie: Übersichtsartikel
Schattauer GmbH

Autoantikörper bei juveniler idiopathischer inflammat orischer Myopathie

Autoantibodies in juvenile idiopathic inflammatory myopathy
J.-B. González-González
1   Labor Berlin – Charité Vivantes GmbH, Fachbereich Autoimmundiagnostik, Berlin
,
C. Meisel
1   Labor Berlin – Charité Vivantes GmbH, Fachbereich Autoimmundiagnostik, Berlin
,
N. Unterwalder
1   Labor Berlin – Charité Vivantes GmbH, Fachbereich Autoimmundiagnostik, Berlin
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
27. Dezember 2017 (online)

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Zusammenfassung

Klassische Myositis-spezifische Autoantikörper (MSA) gegen t-RNA-Synthetasen, Mi-2 und SRP lassen sich nur selten bei juvenilen idiopathischen inflammatorischen Myopathien (JIIM) nachweisen und trugen bisher wenig zur Diagnosestellung bei. Die Entdeckung neuer MSA wie TIF-1 gamma, NXP-2, MDA5 und SAE ermöglicht eine bessere Diagnostik und serologische Klassifikation der JIIM sowie prognostische Aussagen. MSA können bei etwa 60 % der JIIM nachgewiesen werden, wobei Antikörper gegen TIF-1 gamma und NXP-2 am häufigsten sind. Diese sind vor allem mit juveniler Dermatomyositis assoziiert, wobei Patienten mit NXP-2-Antiköpern jünger sind, häufiger eine subkutane Kalzinose entwickeln und einen schwereren Krankheitsverlauf zeigen. Kinder mit MDA5-Antikörper zeigen vorwiegend Hautmanifestationen und eine milde Form der Myositis. SAE-Antikörper sind extrem selten. Die Konzentration von Antikörpern gegen Jo-1, SRP und MDA-5 korreliert mit der Krankheitsaktivität. Das erweiterte Spektrum nachweisbarer MSA könnte in Zukunft die Notwendigkeit invasiver diagnostischer Methoden wie der Muskelbiopsie reduzieren und neue Möglichkeiten zur Therapie -stratifizierung und -überwachung schaffen.

Summary

The classical myositis specific antibodies (MSA) against t-RNA-synthetases, Mi-2, and SRP are infrequently detected in juvenile idipopathic inflammatory myopathy (JIIM) and have contributed little to the diagnosis until now. The discovery of new MSA such as those against TIF-1 gamma, NXP-2, MDA5 and SAE makes possible a better diagnostic and serological classification of JIIM as well as a better prognostic estimation. MSA can be detected in about 60 % of JIIM cases, being antibodies against TIF-1 gamma and NXP-2 the most frequent ones. These are primarily associated with juvenile dermatomyositis. Patients with NXP-2 antibodies are younger, develop more frequently subcutaneous calcinosis and show a more severe disease. Children with MDA5 antibodies show predominantly skin manifestations and a milder form of myositis. SAE antibodies are extremely rare. The concentration of antibodies against Jo-1, SRP and MDA-5 correlates with disease activity. The extended spectrum of detectable MSA might reduce in the future the necessity of invasive diagnostic procedures such as the muscle biopsy and might open new possibilities for the therapeutic stratification and survey.

Schlüsselwörter

Juvenile Myositis - neue Autoantikörper

Keywords

Juvenile myositis - new antibodies
 

  • Literatur

  • 1 Myositissyndrome. Leitlinien für Diagnostik und Therapie in der Neurologie 2012; AWMF-Registernummer 030/054 1-16.
  • 2 Rider LG, Katz JD, Jones OY. Developments in the classification and treatment of the juvenile idiopathic inflammatory myopathies. Rheumatic diseases clinics of North America 2013; 39 (04) 877-904.
    CrossrefPubMedSuche in Google Scholar
  • 3 Rider LG, Shah M, Mamyrova G. et al The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory myopathies. Medicine 2013; 92 (04) 223-243.
    CrossrefPubMedSuche in Google Scholar
  • 4 Tansley SL, Betteridge ZE, McHugh NJ. The diagnostic utility of autoantibodies in adult and juvenile myositis. Current opinion in rheumatology 2013; 25 (06) 772-777.
    CrossrefPubMedSuche in Google Scholar
  • 5 Robinson AB, Reed AM. Clinical features, pathogenesis and treatment of juvenile and adult dermatomyositis. Nature reviews Rheumatology 2011; 7 (11) 664-675.
    CrossrefPubMedSuche in Google Scholar
  • 6 Tansley SL, McHugh NJ. Myositis specific and associated autoantibodies in the diagnosis and management of juvenile and adult idiopathic inflammatory myopathies. Current rheumatology reports 2014; 16 (12) 464.
    CrossrefPubMedSuche in Google Scholar
  • 7 Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). NEJM 1975; 292 (07) 344-347.
    CrossrefPubMedSuche in Google Scholar
  • 8 Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). NEJM 1975; 292 (08) 403-407.
    CrossrefPubMedSuche in Google Scholar
  • 9 Shah M, Mamyrova G, Targoff IN. et al The clinical phenotypes of the juvenile idiopathic inflammatory myopathies. Medicine 2013; 92 (01) 25-41.
    CrossrefPubMedSuche in Google Scholar
  • 10 Stone KB, Oddis CV, Fertig N. et al Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis and rheumatism 2007; 56 (09) 3125-3131.
    CrossrefPubMedSuche in Google Scholar
  • 11 Wang HB, Zhang Y. Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor. Nucleic Acids Res 2001; 29 (12) 2517-2521.
    CrossrefPubMedSuche in Google Scholar
  • 12 Chiu YE, Co DO. Juvenile dermatomyositis: immunopathogenesis, role of myositis-specific autoantibodies, and review of rituximab use. Pediatric dermatology 2011; 28 (04) 357-367.
    CrossrefPubMedSuche in Google Scholar
  • 13 Ghirardello A, Bassi N, Palma L. et al Autoantibodies in polymyositis and dermatomyositis. Current rheumatology reports 2013; 15 (06) 335.
    CrossrefPubMedSuche in Google Scholar
  • 14 Hamaguchi Y, Kuwana M, Hoshino K. et al Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study. Archives of dermatology 2011; 147 (04) 391-398.
    CrossrefPubMedSuche in Google Scholar
  • 15 Satoh T, Okano T, Matsui T. et al Novel autoantibodies against 7SL RNA in patients with polymyositis/dermatomyositis. The Journal of rheumatology 2005; 32 (09) 1727-1733.
    PubMedSuche in Google Scholar
  • 16 Hengstman GJ, van Engelen BG, Vree Egberts WT, van Venrooij WJ. Myositis-specific autoantibodies: overview and recent developments. Current opinion in rheumatology 2001; 13 (06) 476-482.
    CrossrefPubMedSuche in Google Scholar
  • 17 Rouster-Stevens KA, Pachman LM. Autoantibody to signal recognition particle in African American girls with juvenile polymyositis. The Journal of rheumatology 2008; 35 (05) 927-929.
    PubMedSuche in Google Scholar
  • 18 Casciola-Rosen L, Mammen AL. Myositis autoantibodies. Current opinion in rheumatology 2012; 24 (06) 602-608.
    CrossrefPubMedSuche in Google Scholar
  • 19 Suzuki S, Ohta M, Shimizu Y. et al Anti-signal recognition particle myopathy in the first decade of life. Pediatric neurology 2011; 45 (02) 114-116.
    CrossrefPubMedSuche in Google Scholar
  • 20 Momomura M, Miyamae T, Nozawa T. et al Serum levels of anti-SRP54 antibodies reflect disease activity of necrotizing myopathy in a child treated effectively with combinatorial methylprednisolone pulses and plasma exchanges followed by intravenous cyclophosphamide. Modern rheumatology/the Japan Rheumatism Association 2014; 24 (03) 529-531.
    Suche in Google Scholar
  • 21 Targoff IN, Mamyrova G, Trieu EP. et al A novel autoantibody to a 155-kd protein is associated with dermatomyositis. Arthritis and rheumatism 2006; 54 (11) 3682-3689.
    CrossrefPubMedSuche in Google Scholar
  • 22 Gunawardena H, Wedderburn LR, North J. et al Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis. Rheumatology 2008; 47 (03) 324-328.
    PubMedSuche in Google Scholar
  • 23 Trallero-Araguas E, Rodrigo-Pendas JA, Selva-O’Callaghan A. et al Usefulness of anti-p155 autoantibody for diagnosing cancer-associated dermatomyositis: a systematic review and meta-analysis. Arthritis and rheumatism 2012; 64 (02) 523-532.
    CrossrefPubMedSuche in Google Scholar
  • 24 Espada G, Maldonado Cocco JA, Fertig N, Oddis CV. Clinical and serologic characterization of an Argentine pediatric myositis cohort: identification of a novel autoantibody (anti-MJ) to a 142-kDa protein. The Journal of rheumatology 2009; 36 (11) 2547-2551.
    CrossrefPubMedSuche in Google Scholar
  • 25 Ceribelli A, Fredi M, Taraborelli M. et al Anti-MJ/NXP-2 autoantibody specificity in a cohort of adult Italian patients with polymyositis/dermatomyositis. Arthritis research & therapy 2012; 14 (02) R97.
    CrossrefPubMedSuche in Google Scholar
  • 26 Ichimura Y, Matsushita T, Hamaguchi Y. et al Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: possible association with malignancy. Annals of the rheumatic diseases 2012; 71 (05) 710-713.
    CrossrefPubMedSuche in Google Scholar
  • 27 Tansley SL, Betteridge ZE, Shaddick G. et al Calcinosis in juvenile dermatomyositis is influenced by both anti-NXP2 autoantibody status and age at disease onset. Rheumatology 2014; 53 (12) 2204-2208.
    CrossrefPubMedSuche in Google Scholar
  • 28 Tansley SL, Betteridge ZE, Gunawardena H. et al Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study. Arthritis research & therapy 2014; 16 (04) R138.
    CrossrefPubMedSuche in Google Scholar
  • 29 Sato S, Hoshino K, Satoh T. et al RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease. Arthritis and rheumatism 2009; 60 (07) 2193-2200.
    CrossrefPubMedSuche in Google Scholar
  • 30 Nakashima R, Imura Y, Kobayashi S. et al The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody. Rheumatology 2010; 49 (03) 433-440.
    CrossrefPubMedSuche in Google Scholar
  • 31 Fiorentino D, Chung L, Zwerner J. et al The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): a retrospective study. Journal of the American Academy of Dermatology 2011; 65 (01) 25-34.
    CrossrefPubMedSuche in Google Scholar
  • 32 Hall JC, Casciola-Rosen L, Samedy LA. et al Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum. Arthritis care & research 2013; 65 (08) 1307-1315.
    CrossrefPubMedSuche in Google Scholar
  • 33 Betteridge Z, Gunawardena H, North J. et al Identification of a novel autoantibody directed against small ubiquitin-like modifier activating enzyme in dermatomyositis. Arthritis and rheumatism 2007; 56 (09) 3132-3137.
    CrossrefPubMedSuche in Google Scholar
  • 34 Betteridge ZE, Gunawardena H, Chinoy H. et al Clinical and human leucocyte antigen class II haplotype associations of autoantibodies to small ubiquitin-like modifier enzyme, a dermatomyositis-specific autoantigen target, in UK Caucasian adult-onset myositis. Annals of the rheumatic diseases 2009; 68 (10) 1621-1625.
    CrossrefPubMedSuche in Google Scholar
  • 35 Tarricone E, Ghirardello A, Rampudda M. et al Anti-SAE antibodies in autoimmune myositis: identification by unlabelled protein immunoprecipitation in an Italian patient cohort. Journal of immunological methods 2012; 384 1-2 128-134.
    CrossrefPubMedSuche in Google Scholar
  • 36 Muro Y, Sugiura K, Akiyama M. Low prevalence of anti-small ubiquitin-like modifier activating enzyme antibodies in dermatomyositis patients. Autoimmunity 2013; 46 (04) 279-284.
    CrossrefPubMedSuche in Google Scholar
  • 37 Marie I, Hatron PY, Dominique S. et al Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody. Seminars in arthritis and rheumatism 2012; 41 (06) 890-899.
    CrossrefPubMedSuche in Google Scholar
  • 38 Benveniste O, Drouot L, Jouen F. et al Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy. Arthritis and rheumatism 2011; 63 (07) 1961-1971.
    CrossrefPubMedSuche in Google Scholar
  • 39 Tansley SL, McHugh NJ, Wedderburn LR. Adult and juvenile dermatomyositis: are the distinct clinical features explained by our current understanding of serological subgroups and pathogenic mechanisms?. Arthritis research & therapy 2013; 15 (02) 211.
    CrossrefPubMedSuche in Google Scholar
  • 40 Baechler EC, Bilgic H, Reed AM. Type I interferon pathway in adult and juvenile dermatomyositis. Arthritis research & therapy 2011; 13 (06) 249.
    CrossrefPubMedSuche in Google Scholar