Autoantibodies reactive with small ribonucleoprotein antigens: a convergence of molecular biology and clinical immunology.
Autoantibodies to nuclear antigens (ANA) occur in patients with systemic lupus erythematosus (SLE) and other multisystem autoimmune diseases. Although heterogeneous, there are 2 major groups, autoantibodies to DNA and autoantibodies to non-DNA antigens, the latter including ANAs to the soluble or "extractable nuclear antigens" (ENA). This review discusses those ENAs which are ribonucleoproteins (RNPs) consisting of small RNA molecules (80-400 nucleotides) attached to non-histone proteins: these are called small nuclear (sn) or small cytoplasmic (sc) ribonucleoproteins according to their location in the cell and at least some are known to play an important role in nuclear metabolism. ENAs can be immunoprecipitated from crude preparations of nuclei by sera from patients with multisystem autoimmune diseases and, after removal of the associated proteins, the RNA components can be analyzed by gel electrophoresis. This shows 3 main categories of small RNAs: the U group comprising U1-U6 snRNAs, the Ro group comprising small nucleocytoplasmic RNAs, and the La group comprising several species of cellular snRNAs as well as the Ro scRNAs. La, in addition, includes small RNAs encoded by adenovirus (VA I, VA II), Epstein-Barr virus (EBER 1, EBER 2) and vesicular stomatitis virus (leader RNA). In the case of each group, the RNAs themselves are not antigenic but become so when associated with proteins, most of which are uncharacterized. The U snRNAs, located in the nucleus, are transcribed by RNA polymerase II and appear to be involved in the splicing of introns from mRNA. Sera from patients with mixed connective tissue disease (MCTD) react with RNPs containing U1 RNA and sera from patients with SLE react with U RNPs containing U1, U2, U4, U5 and U6 RNAs, collectively known as the Sm antigen. The Ro RNAs are transcribed by RNA polymerase III and have no known function. Sera from patients with primary Sjögren's syndrome and some cases of SLE react with Ro scRNPs. The La RNAs are also transcribed by RNA polymerase III and are located mostly in the nucleus; functionally the protein associated with the La RNAs appears to be important in RNA polymerase III transcription. Sera from patients with primary Sjögren's syndrome react with the heterogeneous group of both cellular and viral RNAs which constitute the La RNP antigen. Sera of patients with SLE, scleroderma, polymyositis and dermatomyositis also react with RNPs relevant to nuclear metabolism and further definition of these RNPs is awaited. Many advances can be expected from the convergence of molecular biology and clinical immunology exemplified by the current studies on ENAs.(ABSTRACT TRUNCATED AT 400 WORDS)
D000974:Antibodies, Antinuclear / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D012313:RNA / Q000235:genetics / Q000276:immunology; D020733:RNA, Small Cytoplasmic; D012342:RNA, Small Nuclear; D012367:RNA, Viral / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen
D000974:Antibodies, Antinuclear; D000941:Antigens; D001323:Autoantibodies; D001324:Autoantigens; D012313:RNA; D020733:RNA, Small Cytoplasmic; D012342:RNA, Small Nuclear; D012367:RNA, Viral; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen; C116006:RO60 protein, human