Two nuclear dot-associated proteins, PML and Sp100, are often co-autoimmunogenic in patients with primary biliary...

The nucleoproteins Sp100 and PML, the first an autoantigen predominant in patients with primary biliary cirrhosis (PBC) and the second a transformation and cell growth suppressing protein aberrantly expressed in promyelocytic leukaemia cells, were recently shown to colocalize in dot-like nuclear domains. Here we analysed whether PML, like Sp100, is also an autoantigen in patients with PBC and other autoimmune diseases, and wether both proteins interact directly. Testing sera from autoimmune patients using an immunoprecipitation assay with radiolabelled PML and an immunofluorescence assay based on a cell line overexpressing PML, autoantibodies (Aabs) against PML were found in the majority o anti-Sp100 Aab positive patients. Only very few patients with PBC or other autoimmune diseases contained anti-PML or anti-Sp100 Aabs exclusively. In contrast to Sp100, immunoreactivity of recombinant PML in immunoblots was only weak and was directed to one region. This suggests that anti-PML Aabs recognize fewer and preferentially conformation-dependent epitopes. In an immunoprecipitation assay using in vitro synthesized Sp100 and PML proteins and Abs to recombinant proteins, no direct interaction was observed. Taken together, these data indicate that Aabs against PML are as highly prevalent and specific for patients with PBC as those against Sp100. The colocalization of these autoantigens and the frequent co-occurrence of the corresponding Aabs might reflect an association of both proteins mediated by one or several other proteins.