RNP-68K (Sm-Free)

Anti-RNP antibodies were found in the sera of mixed connective tissue disease (MCTD) patients, and when these antibodies occur at high titre and in the absence of Sm, they are a good marker for MCTD. Such autoantibodies are also known to occur in the sera of patients with a range of other rheumatic diseases including progressive systemic sclerosis, rheumatoid arthritis, discoid lupus erythematosus, Sjögren's syndrome and various overlapping conditions.

The snRNPs are a group of nuclear particles comprised of several polypeptides associated with a small nuclear RNA molecule.  The most abundant snRNPs are involved in pre-mRNA-splicing. At least 13 different snRNAs have been identified in mammalian cells. Whereas autoantibodies directed against Sm are able to precipitate a wide range of snRNAs, RNP autoantibodies are only able to precipitate one particular type, referred to as U1snRNA. Anti-RNP antibodies react with the U1 snRNP-specific polypeptides (68K, A and C antigens) whereas anti-Sm antibodies react with polypeptides associated with U1, U2, U5 and U4/U6 snRNAs (B,B', D, E, F and G antigens).

Current methods for the detection of autoantibodies to RNP often require the simultaneous determination of reactivity to both RNP/Sm and Sm antigens. The reactivity with Sm is then subtracted from that with RNP/Sm, the difference being considered to be due to RNP-specific autoantibodies. The availability of RNP antigen in the absence of Sm would avoid the necessity for a dual assay to detect anti-RNP antibodies and assays have been reported using isolated U1-RNP specific subunits.

Since the 68K U1-RNP polypeptide constitutes the major MCTD RNP autoantigen, efforts to produce a recombinant RNP antigen have focussed on this subunit, and not the U1-RNP specific subunits A and C which are known to share sequence homology and cross-reactivity with the Sm antigen B/B.

 

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