Anti polymyositis/scleroderma (PM/Scl) autoantibodies are often detected in sera of patients with idiopathic inflammatory myopathies (IIM), scleroderma, and the PM/Scl overlap syndrome, although some anti-PM/Scl-positive patients may not have either of these syndromes [1–4]. The antigenic complex recognized by the PM/Scl autoantibodies has been reported to consist of 11 to 16 proteins, with molecular weights ranging from 20 to 110 kDa found in SDS–PAGE [5,6].
Most anti-PM/Scl-positive sera are reactive with a 100–110 kDa protein, while some also recognize a 75–80 kDa protein [5–7]. Complementary DNA cloning of both autoantigens revealed that the major one is a polypeptide of 100 kDa (referred to as PM/Scl-100) [8,9] and that the 75–80 kDa one (referred to as PM/Scl-75) is a 39 kDa acidic polypeptide that migrates aberrantly in SDS–PAGE .
Recently, it was discovered that the PM/Scl-100 and -75 autoantigens are related to the Escherichia coli exoribonu cleases D and PH, respectively . The nucleolar localization of the PM/Scl complex suggested a role in ribosome synthesis , and, indeed, it was found that the yeast homologue of PM/Scl-100, Rrp6p, is involved in the maturation of 5.8S ribosomal RNA . Moreover, a yeast complex, named the exosome, consisting of 11 3' → 5' exoribonucleases, including Rrp45p (the yeast homologue of PM/Scl-75) and Rrp6p, has been characterized [14–16]. In yeast, the exosome was shown to degrade or process RNA species in the nucleus as well as in the cytoplasm [15,17–20].
In human cells, a complex similar in size to the yeast exosome has been shown to contain both the PM/Scl autoantigens and the human homologue of the yeast exosome component Rrp4p . This finding indicates that the human PM/Scl complex is related to the yeast exosome, and it is therefore referred to as the human exosome (reviewed in ). Recently, cDNAs encoding three novel components of the human exosome (hRrp40p, hRrp41p, and hRrp46p) were isolated and were shown to be associated with the PM/Scl-100 autoantigen and hRrp4p . Furthermore, cDNAs encoding four additional human proteins with homology to yeast exosome components have been isolated, although conclusive evidence for their physical association with the PM/Scl complex is still lacking [4,23–25].
Our aim in this study was to assess whether autoantibodies target other components of the human exosome than the PM/Scl-100 and PM/Scl-75 autoantigens.