The SS-A/Ro 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 SS-A/Ro 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 positive 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 SS-A/Ro antigen is composed of an RNA particle rich in uridine, bound with a 60 kDa protein(7); another 52 kDa protein participates in the complex via a protein-protein interaction.(8)
The SS-B/La antigen is composed of an RNA particle and a 48 kDa phosphoprotein.(9) There are no direct interactions between the two antigens; in fact, the binding sites are independent and the relative autoantibodies, anti-SS-A/Ro and anti-SS-B/La, are not cross-reactive. The localization of the two antigens is both nuclear and cytoplasmic.
The anti-SS-A/Ro autoantibodies are class IgG polyclonal antibodies that recognize conformational epitopes on the 60 kDa molecule, and, to a lesser degree, on the 52 kDa molecule. About one-half of anti-SS-A/Ro sera contains antibodies directed against the two components; the other half presents autoantibodies directed only against one or the other of the two antigens. Some authors report that the 52 kDa anti-SS-A/Ro antibodies alone would be present almost exclusively in subjects affected with Sjogren’s Syndrome (SS), while the 60 kDa anti-SS-A/Ro antibodies would be found only in subjects affected with SLE.(10,11,12)
The anti-SS-B/La antibodies are also polyclonal, class IgG antibodies, and recognize various epitopes, both linear and conformational.(13) The anti-SS-A/Ro antibodies generally present alone, while the anti-SS-B/La antibodies are almost always found in association with the anti-SS-A/Ro antibodies.(14)
The anti-SSA/Ro autoantibodies are most frequently associated with primary SS (60-90%) or with other connective tissue diseases, but may also be found in SLE (15-50%) and, to a lesser degree, in other connective tissue diseases. They may also be found in patients with rheumatoid arthritis or primitive biliary cirrhosis. This data highlights how the anti-SS-A/Ro antibodies are the antibodies most frequently found in cases of systemic autoimmune diseases. In the sera of pregnant women, the anti-SS-A/Ro antibodies can cause development of the so-called neonatal lupus, the primary and most serious clinical manifestation of which is congenital complete atrioventricular block.
The anti-SS-B/La autoantibodies are most frequently found in primitive SS (30-90%) or secondary SS (above all if associated with SLE, 5-40%) and much more rarely in other connective tissue disorders.
- 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.
- PJ Venables, PR Smith, RN Maini. Purification and characterization of the Sjögren’s syndrome A and B antigens. Clin Exp Immunol 1983; 54: 731-8.
- E Ben-Chetrit, EKL Chan, KF Sullivan, EM Tan. A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J Exp Med 1988;167:1560-71.
- RL Slobbe, GJM Pruijn, van Venrooij WJ. Ro (SS-A) and La (SS-B) ribonucleoprotein complexes . structure, function and antigenicity. Ann Med Interne 1991; 142: 592-600.
- E Ben-Chetrit, R Fox, EM Tan. Dissociation of immune responses to the SS-A(Ro) 52-kD and 60-kD polypeptides in systemic lupus erythematosus and Sjögren’s syndrome. Arthr Rheum 1990; 33: 349-55.
- RL Slobbe, GJM Pruijn, WG Damen, JW van der Kemp, WJ van Venrooij. Detection and occurrence of 60 and 52 kD Ro (SS-A) antigens and of autoantibodies against these proteins. Clin Exp Immunol 1991; 86: 99-105.
- JG Routzias, AG Tzioufas, M Sakarellos-Daitsiotis, C Sakarellos, HM Moutsopoulos. Epitope mapping of the Ro/SSa 60 kD autoantigen reveals disease-specific antibody binding profiles. Eur J Clin Invest 1996; 26 : 514-21.
- RH Scofied, AD Farris, AC Horsfall, JB Harley. Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins. Arthritis Rheum 1999; 42: 199-209.
- AG Tzioufas, HM Moutsopoulos. Clinical significance of autoantibodies to SS/A and La/SSB. In : van Venrooij WJ, Maini RN, eds. Manual of Biological Markers of Disease. Dordrecht : Kluwer Academic Publ 1996; C4.1 : 1-14.