The Scl-70 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 Scl-70 (DNA topoisomerase I) antigen 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 anti-topoisomerase I or anti-Scl-70 antibodies, together with the anti-centromeres (ACAs) and the anti-RNA polymerase IIIs (RNAPs), are the autoantibodies most frequently detectable in the serum of patients affected with systemic sclerosis (SSc).(7,8,9,10) SSc presents in localized form and in systemic form(11); the systemic form can, in turn, be subdivided into a limited form (lcSSc) and a diffuse form (dcSSc).(11,12) The anti-Scl-70 antibodies are most frequently associated with dcSSc.
Topoisomerase I is an enzyme whose function is to modify the superstructure of native DNA. Topoisomerase I is a 765 AA polypeptide localized in the nucleoplasm, in the nucleolus, and in the chromosomes.(13) At least 6 immunodominant epitopes have been highlighted in the molecule; two of these are recognized by the majority of the autoantibodies present in the sera of patients.(14)
The anti-Scl-70s are made up of all IgG sub-classes of IgG,(15) by IgA, and less frequently by IgM,(16) and are present in 20-40% of patients affected with SSc. The association between dcSSc and the presence of anti-Scl-70 and DRB1*11 represents a high risk factor for pulmonary involvement in the disease.(17) The prognosis for patients with anti-Scl-70 is more unfavorable due to the frequent association with cardiac failure secondary to pulmonary distress.(18) Since the specificity of these autoantibodies is close to 100%, they play a fundamental role in diagnosis of SSc.
- 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.
- Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis ( scleroderma ). Arthritis Rheum 1980; 23 : 581-90.
- HJ Lakomek, HH Guldner, FA Bautz, G Goerz, P Kind, M Mensing, et al. Nuclear antibodies as serologic markers in progressive systemic scleroderma. Hautarzt 1987; 38: 63-9
- CC Bunn, CP Denton, X Shi-Wen, C Knight, CM Black. Anti-RNA polymerases and other autoantibody specificities in systemic sclerosis. Br J Rheumatol 1998; 37: 15-20.
- D Vazquez-Abad, NF Autoantibodies in systemic sclerosis. Int Rev Immunol 1995; 12: 145-57.
- EC Le Roy, T Krieg, C Black, TA Jr Medsger, R Fleischmajer, N Rowell, et al. Scleroderma ( Systemic Sclerosis ) : classification, subsets and pathogenesis. J Rheumatol 1988; 15 : 202-5.
- RL Humbel. Auto-immunité, auto-anticorps et maladie auto-immunes. In : Humbel RL, ed. Autoanticorps et maladies autoimmunes, Paris: Elsevier 1997. pp. 71-3.
- P D’Arpa, PS Machlin, H Ratie, NF Rothfield, DW Cleveland, WC Earnshaw. cDNA cloning of human topoisomerase I. Catalytic activity of a 67.7 kDa carboxyl-terminal fragment. Proc Natl Acad Sci USA; 85: 2543-7.
- P D’Arpa, H White-Cooper, DW Cleveland, NF Rothfield, WC Earnshaw. Use of molecular cloning methods to map the distribution of epitopes on topoisomerase I ( Scl-70 ) recognized by sera of scleroderma patients. Arthritis Rheum 1990; 33: 1501-11.
- C Bona, N Rothfield. Autoantibodies in scleroderma and tightskin mice. Curr Opin immunol 1994; 6: 931-7.
- D Vazquez-Abad,CA Russell, SM Cusick, WC Earnshaw, NF Longitudinal study of anticentromere and antitopoisomerase I isotypes. Clin Immunol Immunopathol 1995; 74: 257-70.
- GC Fanning, KI Welsh, C Bunn, A Du Bois, CM Block. HLA association in three mutually exclusive autoantibody subgroups in UK systemic sclerosis patients. Br J Rheumatl 1998; 37: 201-7.
- D Basu, JD Reveille. Anti-Scl-70. Autoimmunity 2005; 38: 65-72.