Small nuclear ribonucleoprotein (snRNP) particles are a class of RNA-containing particles in the nucleus of eukaryotic cells. Sera from patients with connective tissue diseases often contain antibodies against the proteins present in these snRNPs. Antibodies against the RNA components of snRNPs, the U snRNAs, are thought to be rare.We tested 118 anti-snRNP sera for the presence of antisnRNA antibodies and found them in 45 sera (38%). In all sera the antibodies (IgG and F(ab)2 fragments thereof) were exclusively directed against Ul snRNA.The anti-(Ul)RNA antibodies were always accompanied by anti-(Ul)RNP antibodies but were not found in sera which contain antibodies of the Sm serotype directed against all nucleoplasmic U snRNP particles. Like anti-RNP antibodies, anti-Ul RNA activity is confined to sera from patients with SLE or SLE overlap syndromes and is rarely found in patients with other connective tissue diseases. By analyzing binding to subfragments of Ul snRNA made in vitro, it was demonstrated that anti-(Ul)RNA antibodies recognize epitopes distributed throughout the Ul RNA molecule. In most sera, however, either the second or the fourth hairpin loop is the main target of the antibody.The possible mechanisms that could lead to the production of this new type of autoantibody are discussed. (J. Clin. Invest.

Objective. To evaluate correlations between changes in a n t i 4 1 RNA antibody levels and disease activity in 9 patients with systemic lupus erythematosus (SLE) overlap syndrome who were prospectively followed up for at least 3 years.Methods. Anti-U1 RNA antibody levels were measured quantitatively, using a nitrocellulose filter binding assay. Disease activity was measured with a validated SLE activity index.Results. All 9 major disease exacerbations were associated with peaks in a n t i 4 1 RNA antibody level.Conclusion. These results seem to indicate that measuring a n t i 4 1 RNA antibody levels can be useful for monitoring disease activity.Sera from patients with connective tissue diseases often contain antibodies against proteins present in small nuclear ribonucleoprotein (snRNP) particles (1). These snRNPs contain a uridine-rich RNA and

Antibodies against naked U1RNA can be found in sera from patients with overlap syndromes of systemic lupus erythematosus (SLE) in addition to antibodies directed to the proteins of U1 ribonucleoproteins (U1RNP). We investigated the reactivity of these U1RNA specific autoantibodies with the native U1RNP particle both in vitro and inside the cell. For this purpose a method was developed to purify human autoantibodies directed to specific regions of U1RNA. The antibodies are specifically directed to either stemloop II or stemloop IV of U1RNA and do not crossreact with protein components of U1RNP. Both types of antibody are able to precipitate from cell extracts native U1snRNPs containing most, if not all, protein components. Immunofluorescence patterns indicate that the antigenic sites on the RNA, i.e. the stem of stemloop II and the loop of stemloop IV, are also available after fixation of the cells. Immunoelectron microscopy employing anti-stemloop IV antibodies and purified, complete U1snRNP particles showed that stemloop IV is located within the body of the U1RNP complex, which also comprises the Sm site and the common Sm proteins. The anti-U1RNA autoantibodies described in this paper recognize native U1RNP particles within the cell and can therefore be used as tools to study mechanisms involved in splicing of pre-mRNA.

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