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What is U1 RNP?

U1-RNP is a uridine-rich small nuclear ribonucleoprotein (snRNP) that consists of U1-RNA and U1-specific polypeptides 70 kD, A, and C. U1-RNP is one of the spliceosomal snRNP complexes (U1, U2, U4/U6, U5, others) whose function is to assist in splicing premessenger RNA to mature spliced RNA. Patients with MCTD form high titers of antibodies against U1-RNP, particularly U1-70kD and U1-RNA, but also polypeptides A and C, producing a high-titer ANA with a speckled pattern. Patients with MCTD appear to mount an antigen-driven immune response directed against U1-RNP, especially against an immunodominant epitope on the 70-kD polypeptide. One hypothesis is that a genetically predisposed (i.e., HLA-DR4) individual mounts a specific immune response against a microbial antigen (cytomegalovirus glycoprotein) that cross-reacts with U1-70kD peptide, which has been modified during cellular apoptosis. Anti-U1-RNP antibodies can be present in other autoimmune diseases such as SLE and SSc, but typically in lower titer.

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