Novel specificity of anti-U1A autoimmune patient sera.

We have previously described a novel complex of proteins which contains the U1snRNP-A protein (U1A) but no other small nuclear ribonucleoprotein particle (snRNP) components (O'Connor et al., RNA 1997;3:1444-55). Antibodies to this novel complex inhibit both splicing and polyadenylation in vitro of a test pre-mRNA (O'Connor et al., RNA 1997;3:1444-55; Lutz et al., RNA 1998;4:1493-9). This novel complex of proteins was identified using an unusual mouse monoclonal antibody (MoAb), called MAb 12E12. We were interested to know if autoimmune patient sera were similar to this MoAb. We have discovered a novel specificity of systemic lupus erythematosus patient sera reminiscent of MAb 12E12 in that the patient serum, like 12E12, (1) does not recognize U1A when bound to U1 RNA, (2) recognizes primarily the epitopes in the amino-terminal third of the protein, including RNA recognition motif 1 (RRM1) and (3) inhibits in vitro polyadenylation. These findings may lead to the discovery of previously undescribed autoantigens as components of the novel protein complex, and may provide insight into autoimmune diseases.