Conclusion
ACA are directed towards centromeric proteins (CENP) with M.W. of 17 KD (CENP-A), 80 KD (CENP-B) and 140 KD (CENP-C). At least 6 epitopes on these proteins are recognized by ACA, but CENP-B (that has been partially cloned) seems to be the primary autoantigen. ACA are clinically associated with the CREST syndrome or limited cutaneous systemic sclerosis (prevalence ±55%), and are also found in 30% of patients with primary biliary cirrhosis (who demonstrate additionally symptoms of CREST), in a small proportion of patients with proximal scleroderma, but hardly in any other condition. The presence of ACA in patients presenting with Raynaud's phenomenon has strong predictive value for the evolution to limited cutaneous systemic sclerosis including CREST.
References
Beck, J.S. Variations in the morphological pattern of “autoimmune” nuclear fluorescence. Lancet 1961, i, 1203–1205.
Moroi, Y., Peebles, C., Fritzler, M.J., Steigerwald, J., Tan, E.M. Autoantibody to centromere (kinetochore) in scleroderma sera. Proc Natl Acad Sci USA 1980, 77, 1627–1631.
Kallenberg, C.G.M., Van der Meulen, J., Pastoor, G., Snijder, J.A.M., Feltkamp, T.E.W., The, T.H. Human fibroblasts, a convenient nuclear substrate for detection of antinuclear antibodies including anti-centromere antibodies. Scand J Rheumatol 1983, 12, 193–200.
Guldner, H.H., Lakomek, H.J., Bautz, F.A. Human anti-centromere sera recognize a 19.5 KD non-histone chromosomal protein from HeLa cells. Clin Exp Immunol 1984, 58, 13–20.
Van Venrooij, W.J., Stapel, S.O., Houben, H., Habets, W.J., Kallenberg, C.G.M., Penner, E., van de Putte, L.B. Scl-86, a marker antigen for diffuse scleroderma. J Clin Invest 1985, 75, 1053–1060.
Earnshaw, W.C., Rothfield, N.F. Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma. Chromosoma (Berl.) 1985, 91, 313–321.
Earnshaw, W.C., Bordwell, B., Marino, C., Rothfield, N. Three human chromosomal autoantigens are recognized by sera from patients with anti-centromere antibodies. J Clin Invest 1986, 77, 426–430.
Earnshaw, W.C., Sullivan, K.F., Machlin, P.S., Cooke, C.A., Kaiser, D.A., Pollard, Th.D., Rothfield, N.F., Cleveland, D.W. Molecular cloning of cDNA for CENP-B, the major human centromere autoantigen. J Cell Biol 1987, 104, 817–829.
Earnshaw, W.C., Machlin, P.S., Bordwell, B.J., Rothfield, N.F., Cleveland, D.W. Analysis of anticentromere autoantibodies using cloned autoantigen CENP-B. Proc Natl Acad Sci USA 1987, 84, 4979–4983.
Rothfield, N., Whitaker, D., Bordwell, B., Weiner, E., Senecal, J.L., Earnshaw, W. Detection of anticentromere antibodies using cloned autoantigen CENP-B. Arthritis Rheum 1987, 30, 1416–1419.
Tan, E.M., Rodnan, G.P., Garcia, I., Moroi, Y., Fritzler, M.J., Peebles, C. Diversity of antinuclear antibodies in progressive systemic sclerosis. Arthritis Rheum 1980, 23, 617–625.
Fritzler, M.J., Kinsella, T.D., Garbutt, E. The CREST syndrome: a distinct serologic entity with anticentromere antibodies.
Shero, J.H., Bordwell, B., Rothfield, N.F., Earnshaw, W.C. Autoantibodies to topoisomerase I are found in sera from scleroderma patients. Science 1986, 231, 737–740.
Kallenberg, C.G.M., Pastoor, G.W., Wouda, A.A., The, T.H. Antinuclear antibodies in patients with Raynaud's phenomenon: clinical significance of anticentromere antibodies. Ann Rheum Dis 1982, 41, 382–387.
Catoggio, L.J., Bernstein, R.M., Black, C.M., Hughes, G.R.V., Maddison, P.J. Serological markers in progressive systemic sclerosis: clinical correlations. Ann Rheum Dis 1983, 42, 23–27.
Steen, V.D., Ziegler, G.L., Rodnan, G.P., Medsger, T.A. Jr. Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis. Arthritis Rheum 1984, 27, 125–131.
Tramposch, H.D., Smith, C.D., Senecal, J.L., Rothfield, N. A longterm longitudinal study of anticentromere antibodies. Arthritis Rheum 1984, 27, 121–124.
Sarkozi, J., Bookman, A.A.M., Lee, P., Keystone, E.C., Fritzler, M. J. Significance of anticentromere antibody in idiopathic Raynaud's syndrome. Am J Med 1987, 83, 893–898.
Weiner, E.S., Earnshaw, W.C., Senecal, J.L., Bordwell, B., Johnson, P., Rothfield, N.F. Clinical association of anticentromere antibodies and anti-bodies to topoisomerase I. Arthritis Rheum 1988, 31, 378–385.
LeRoy, E.C. et al. (editorial). Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988, 15, 202–205.
Makinen, D., Fritzler, M., Davis, P., Sherlock, S. Anticentromere antibodies in primary biliary cirrhosis. Arthritis Rheum 1983, 26, 914–917.
Kallenberg, C.G.M., Limburg, P.C., The, T.H. Diagnostic and prognostic significance of anticentromere antibodies (ACA). Protides Biol Fluids Ed: Peeters, H., Pergamon Press, Oxford, 1985, 359–360.
Powell, F.C., Schroeter, A.L., Dickson, E.R. Primary biliary cirrhosis and the CREST syndrome: a report of 22 cases. Q J Med 1987, 237, 75–82.
Kallenberg, C.G.M., Wouda, A.A., Hoet, M.H. van Venrooij, W. J. Development of connective tissue disease in patients presenting with Raynaud's phenomenon: a six year follow-up with emphasis on the predictive value of antinuclear antibodies as detected by immunoblotting. Ann Rheum Dis 1988, 47, 634–641.
References
van der Woude, F.J., et al. - Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet i 1985, 425–429.
Savage, C.O.C., et al.- Prospective study of radio-immunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis. Lancet i: 1987, 1389–1393.
Nagata, N., et al.- Specific sensitization of Lyt-1 + 2- T cells to spleen cells modified by drug d-penicillamine or a stereoisomer. J Immunol 1986, 136, 136–142.
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Kallenberg, C.G.M. Anti-centromere antibodies (ACA). Clin Rheumatol 9 (Suppl 1), 136–140 (1990). https://doi.org/10.1007/BF02205562
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DOI: https://doi.org/10.1007/BF02205562