Immunolocalization and partial characterization of a nucleolar autoantigen (PM-Scl) associated with polymyositis/scleroderma overlap syndromes.

The Journal of Immunology (Impact Factor: 5.36). 01/1987; 137(12):3802-8.
Source: PubMed

ABSTRACT Precipitating anti-PM-Scl antibodies are present in sera from patients with polymyositis, scleroderma, and polymyositis/scleroderma overlap syndromes. By indirect immunofluorescence microscopy, anti-PM-Scl antibodies stained the nucleolus in cells of different tissues and species, suggesting that the antigen is highly conserved. By electron microscopy, anti-PM-Scl antibodies reacted primarily with the granular component of the nucleolus. Drugs that inhibit rRNA synthesis had a marked effect on the expression of PM-Scl antigen. In actinomycin D-treated cells, immunofluorescence staining by anti-PM-Scl was significantly reduced with residual staining restricted to the granular regions of nucleoli. Treatment with 5,6-dichloro-beta-D-ribofuranosylbenzimidazole (DRB) also selectively reduced nucleolar staining. On a molecular level, anti-PM-Scl antibodies precipitated 11 polypeptides with molecular weights (Mr) ranging from 110,000 to 20,000. The Mr 80,000 and 20,000 polypeptides were phosphorylated. Evidence suggests that the PM-Scl antigen complex may be related to a preribosomal particle.

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    ABSTRACT: Four distinct nucleolar proteins or RNA-protein complexes have recently been identified as targets of human autoimmune antibodies. These autoantigens areRNA polymer-ase I, PM-Scl (a particle possibly related to preribosomes), 7-2 RNP andfibrillarin (a U3-RNP associated protein). The four different nucleolar autoantigens could be assigned to distinct nucleolar subcompartments by light and electron microscopic immunocytochemistry. RNA polymerase I was located in the fibrillar centers, PM-Scl antigen and 7-2 RNP in the granular component and fibrillarin in the dense fibrillar component. Experimental evidence suggests that these naturally occurring antibodies could be helpful tools in further studying nucleolus structure and functions as well as molecular mechanisms involved in ribosome biogenesis. From a clinical viewpoint, we believe that it is important to identify the nature of reactive autoantigens in systemic autoimmune diseases in order to answer questions concerning the mechanisms which render conserved ubiquitous cellular proteins immunogenic. Revealing such mechanisms in return could give clues with regard to the etiology of certain systemic rheumatic diseases. Ribosome biogenesis, a highly dynamic process with its many well-defined intermediate biological steps related to specific nuclear structures could be amenable for such studies.
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