Apoptotic and necrotic cells are strong candidates as sources of the autoantigens that drive the autoantibody response in systemic lupus erythematosus (SLE). Defects in the physiological mechanisms for the clearance of dying cells may promote disease susceptibility to SLE. Ablation of the mouse gene Dnase1 results in the development of anti-chromatin autoimmunity and glomerulonephritis, indicating that the enzyme protects against autoimmunity by digesting extracellular chromatin.
References
Wakeland, E.K., Wandstrat, A.E., Liu, K. & Morel, L. Curr. Opin. Immunol. 11, 701–707 ( 1999).
Botto, M. et al. Nature Genet. 19, 56– 59 (1998).
Bickerstaff, M.C. et al. Nature Med. 5, 694– 697 (1999).
Boes, M. et al. Proc. Natl Acad. Sci. USA 97, 1184– 1189 (2000).
Ehrenstein, M.R., Cook, H.T. & Neuberger, M.S. J. Exp. Med. 191, 1253– 1258 (2000).
Shultz, L.D., Rajan, T.V. & Greiner, D.L. Trends Biotechnol. 15, 302– 307 (1997).
O'Keefe, T.L., Williams, G.T., Batista, F.D. & Neuberger, M.S. J. Exp. Med. 189, 1307–1313 (1999).
Nishimura, H., Nose, M., Hiai, H., Minato, N. & Honjo, T. Immunity 11, 141– 151 (1999).
Balomenos, D. et al. Nature Med. 6, 171– 176 (2000).
Di Cristofano, A. et al. Science 285, 2122– 2125 (1999).
Salmon, J.E. et al. J. Clin. Invest. 97, 1348– 1354 (1996).
Seligmann, M. C. R. Acad. Sci. (Paris) 245, 243– 245 (1957).
Lachmann, P. Sci. Basis Med. Annu. Rev. 36–58 ( 1967).
Lachmann, P.J. Clin. Exp. Immunol. 106, 187–189 (1996).
Macanovic, M. et al. Clin. Exp. Immunol. 106, 243– 252 (1996).
Davis, J.C. Jr et al. Lupus 8, 68–76 (1999).
Pan, C.Q. et al. J. Biol. Chem. 273, 18374– 18381 (1998).
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Walport, M. Lupus, DNase and defective disposal of cellular debris. Nat Genet 25, 135–136 (2000). https://doi.org/10.1038/75963
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DOI: https://doi.org/10.1038/75963
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