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Autoantibodies directed to novel components of the PM/Scl complex, the human exosome

Rick Brouwer1, Wilma TM Vree Egberts1, Gerald JD Hengstman2, Reinout Raijmakers1, Baziel GM van Engelen2, Hans Peter Seelig3, Manfred Renz3, Rudolf Mierau4, Ekkehard Genth4, Ger JM Pruijn1 and Walther J van Venrooij1*

Author Affiliations

1 Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands

2 Neuromuscular Centre Nijmegen, Institute of Neurology, University Medical Centre St Radboud, Nijmegen, The Netherlands

3 Institute of Immunology and Molecular Genetics, Karlsruhe, Germany

4 Research Institute and Clinic of Rheumatic Diseases, Aachen, Germany

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Arthritis Res 2002, 4:134-138  doi:10.1186/ar389

Published: 12 November 2001


The autoantigenic polymyositis/scleroderma (PM/Scl) complex was recently shown to be the human homologue of the yeast exosome, which is an RNA-processing complex. Our aim was to assess whether, in addition to targeting the known autoantigens PM/Scl-100 and PM/Scl-75, autoantibodies also target recently identified components of the PM/Scl complex. The prevalence of autoantibodies directed to six novel human exosome components (hRrp4p, hRrp40p, hRrp41p, hRrp42p, hRrp46p, hCsl4p) was determined in sera from patients with idiopathic inflammatory myopathy (n = 48), scleroderma (n = 11), or the PM/Scl overlap syndrome (n = 10). The sera were analyzed by enzyme-linked immunosorbent assays and western blotting using the affinity-purified recombinant proteins. Our results show that each human exosome component is recognized by autoantibodies. The hRrp4p and hRrp42p components were most frequently targeted. The presence of autoantibodies directed to the novel components of the human exosome was correlated with the presence of the anti-PM/Scl-100 autoantibody in the sera of patients with idiopathic inflammatory myopathy (IIM), as was previously found for the anti-PM/Scl-75 autoantibody. Other clear associations between autoantibody activities were not found. These results further support the conception that the autoimmune response may initially be directed to PM/Scl-100, whereas intermolecular epitope spreading may have caused the autoantibody response directed to the associated components.

anti-PM/Scl; autoantibody; autoantigen; exosome complex