The Centromere B 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 Centromere B 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 centromere consists of a differentiated chromatinic structure made up of DNA and protein complexes assembled in the kinetochore, to which the microtubules bind for correct movement of the chromosomes during the various phases of cell mitosis. The centromeric DNA is associated with specific constitutive proteins (CENP-A, CENP-B, CENP-C, CENP-D, CENP-G, CENP-H) and with helper proteins.
According to recent data, reactivity to CENP-B should also be the principal target of the antibody response to endothelial cells in patients affected with limited cutaneous systemic sclerosis (cSS) or CREST(7); this pathology is the most frequent clinical manifestation in subjects with anti-centromere antibodies (ACA) at positivity percentages of 49-96%.(8) The CREST clinical subset is characterized by a more favorable clinical course and higher survival rate (an average of 93% after 10 years) with respect to the more widespread variant in which ACAs are observed in lower percentages. ACAs are typically associated with the Raynaud’s phenomenon, telangiectasia, and digital ischemic necrosis. Various studies have shown that 25% of patients exhibiting Raynaud’s phenomenon may present with ACA as a prodromal and isolated manifestation of systemic sclerosis; this fact supports the predictive value of ACA testing in relation to the disorder.(8,9,10) ACAs may also be found in other pathologies such as primitive biliary cirrhosis (in 16% of cases) in association with the anti-mitochondrial M2 antibodies, and in other systemic autoimmune diseases such as SLE, SS, UCTD, and RA (with positivity levels of less than 10%).(11,12)
- 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.
- A Servettaz, M Tamby, P Guilpain, J Reinbolt, Y Allanore, A Kahan, et al. Anti-endothelian cell antibodies from patients with limited cutaneous systemic sclerosis bind to centromeric protein B ( CENP-B ). Clin Immunol 2006; 120: 212-9.
- KT Ho, JD Reveille. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther 2003; 5: 80-93.
- E Hachulla, S Dubucquoi. Intéret des anticorps antinucléaires pour le diagnostic, la classification et le prognostic de la sclérodermie systémique.Rev Méd Interne 2004; 25: 442-7.
- M Harris, A Rosen. Autoimmunity in scleroderma: the origin, pathogenetic role, and clinical significance of autoantibodies. Curr Opin Rheumatol 2003; 15: 778-804.
- P Nietert, H Mitchell, M Bolster, S Shaftman, B Tilley, RM Silver. Racial variation in clinical and immunological manifestation of systemic sclerosis. J Rheumatol 2006; 33: 263-8.
- S Miyawaki, H Asanuma, S Nishiyama, Y Yoshinaga. Clinical and serological heterogeneity in patients with anticentromere antibodies. J Rheumatol 2005; 32: 1488-94.