The U1-snRNP test is a chemiluminescent immunoassay (CLIA), for use on IDS automated analyzers. It is used for the quantitative determination of the specific IgG antibodies directed against the U1-snRNP antigens in human samples of serum or plasma (EDTA).
The extractable nuclear anti-antigen (ENA) autoantibodies represent a large family of non-organ- and non-species-specific autoantibodies, detection of which is of great importance in laboratory diagnosis of systemic rheumatic autoimmune diseases. (1,2,3,4)
From the laboratory point of view, systemic autoimmune diseases are characterized by the presence of anti-nuclear autoantibodies (ANAs). ANA is the first autoantibody test ordered for patients with suspected systemic autoimmune disorders. ANA assays are generally conducted by the indirect immunofluorescence (IFI) technique on a monostrate of HEp-2 cells; IFI positivity for ANA indicates the presence of autoantibodies directed against various nuclear antigens (DNA, histones, non-histonic proteins, nuclear antigens, etc.) or cytoplasmic antigens.(5,6) Significantly high-titer positivity for ANAs should be further investigated via testing for anti-ENA and anti-dsDNA autoantibodies. Positivity for ANAs and for one or more specific tests for anti-ENA and/or anti-dsDNA is highly suggestive of systemic autoimmune disorders: systemic lupus erythematosus (SLE), Sjogren’s Syndrome (SS), progressive systemic sclerosis (PSS), dermatomyositis/polymyositis (DM/PM), and/or mixed connective tissue disease (MCTD).
The Sm and RNP antigens are part of a nuclear macromolecular complex made up of RNA and proteins contained in the spliceosome, a nuclear particle of about 60S that is responsible for splicing, the mechanism by which non-coding pre-mRNA sequences are removed.
RNA-associated spliceosomal proteins may be divided into two classes: those constituting the so-called common complex or Sm, and the specific proteins from which each small nuclear RiboNuclearProtein (snRNP) takes its name and which are denominated U1, U2, U4/U6, and U5 snRNP.(7)
While the snRNPs are made up of numerous molecules, only the proteins of the Sm common complex, U1-RNP, and U2-RNP manifest autoantigenic properties.
The anti-Sm antibodies are for the most part directed against the B1, B, and D proteins, the fundamental molecules from the immunological point of view.(8,9) Anti-Sm antibodies are demonstrable in 5-25% of subjects affected with SLE, with a higher frequency among black (African) and Asiatic populations than in white (Caucasian) subjects(10,11); demonstration is one of the ACR criteria for diagnosis of this disease.
Anti-RNP autoantibodies are detectable in 25-47% of patients affected with SLE and in all patients affected with mixed connective tissue disorders. In the majority of cases, the anti-RNP antibodies are directed against the U1-70 kDa and U1-A antigens and only rarely against the U1-C protein. In terms of clinical association, their presence is significantly correlated with Raynaud’s phenomenon and myocarditis. Isolated high-titer occurrence of anti-U1RNP antibodies is characteristic of patients affected with MCTD, for which it represents a fundamental diagnostic criterion even in cases in which the antibody titer does not correlate to the clinical course of the disease.
- CA von Mühlen, EM Tan. Autoantibodies in the diagnosis of systemic rheumatic diseases. Sem Arthr Rheum 1995; 24: 323-58.
- RL Humbel. Auto-immunité, auto-anticorps et maladie. In : Humbel RL, ed. Autoanticorps et maladies autoimmunes, Paris, France : Edition Scientifiques Elsevier; 1997: 17-20.
- PN Hollingsworth, SC Pummer, RL Dawkins. Antinuclear antibodies. In : Peter JB, Shoenfeld Y, eds. Autoantibodies. Amsterdam, The Netherlands : Elsevier Science BV; 1996: 74-90.
- CA Slater, RB Davis, RH Shmerling. Antinuclear antibodies testing. A study of clinical utility. Arch Int Med 1996; 156: 1421-5.
- RL Humbel. Detection of antinuclear antibodies by immunofluorescence. In : van Venrooij, Maini RN eds. Manual of Biological Markers of Disease. Dordrecht, The Netherlands : Kluwer; 1993: A2:1-16.
- National Committee for Clinical Laboratory Standardization. Quality assurance for the indirect immunofluorescence test for autoantibodies to nuclear antigen ( IF-ANA ). Approved Guideline. Wayne, PA: NCCLS I/LA2-A, vol. 16 ( 11 ); 1996.
- CL Will, R Luhrmann. Spliceosomal UsnRNP biogenesis, structure and function. Curr Opin Cell Biol 2001; 13:290-301.
- GW Zieve, PR Khusial. The anti-Sm immune response in autoimmunity and cell biology. Autoimmun Rev 2003; 2: 235-40.
- MT McClain, PA Ramsland, KM Kaufman, JA James. Anti-Sm autoantibodies in systemic lupus erythematosus target highly basic surface structures of complexed spliceosomal autoantigens. J Immunol 2002; 168: 2054-62.
- SL Peng, JE Craft. Spliceosomal snRNPs autoantibodies. In : Peter JB, Shoenfeld Y, eds. Autoantibodies. Amsterdam : Elsevier Science BV, 1996, pages 774-82.
- Y Sherer, A Gorstein, MJ Fritzler, Y Shoenfeld. Autoantibody explosion in systemic lupus erythematosus. Semin Arthritis Rheum 2004; 34: 501-37.