SLE 2 - Clin Exp Immunol 1999 118:322328 Antibodies from...

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Antibodies from systemic lupus erythematosus (SLE) sera define differential release of autoantigens from cell lines undergoing apoptosis M. L. HUGGINS, I. TODD, M. A. CAVERS, S. R. PAVULURI, P. J. TIGHE & R. J. POWELL Division of Molecular and Clinical Immunology, School of Clinical Laboratory Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, UK (Accepted for publication 12 August 1999) SUMMARY SLE is an autoimmune disease characterized by a wide range of anti-cellular and anti-nuclear autoantibodies. Many of these antigens are exposed or altered during apoptosis when the nucleus is dismantled in a controlled manner by caspases. We used Western blotting techniques to demonstrate that autoantibodies in SLE sera recognize antigens released during apoptosis. Reproducible bands, not seen in the untreated cells, with the characteristics of histones were seen when staining apoptotic cell lysates with SLE sera. Normal sera recognized some of these bands but much less strongly. Different triggers of apoptosis did not produce marked differences in the antigens recognized. We also compared different cell lines (Jurkat and U937) and found that the staining differed for one autoantigen in particular. The differential release of autoantigens by apoptotic cells may have relevance to the variety of autoantibodies seen in SLE. Keywords systemic lupus erythematosus apoptosis histones INTRODUCTION SLE is an autoimmune disease characterized by antibodies to a wide range of cellular and nuclear autoantigens, including DNA, ribonu- cleoproteins (Ro, La), poly ADP ribose polymerase (PARP), nucleo- somes and histones [1]. Many of these antigens are exposed or altered during apoptosis, which is an active process leading to the controlled death of cells. Initial membrane changes are followed by the dismantling of the nucleus and other intracellular organelles. Some of the dismantled components are packaged and form on the surface of these apoptotic cells as ‘blebs’. Casciola-Rosen et al . showed by immunofluorescence that antibodies in sera from SLE patients were able to recognize antigens contained within these blebs and hypothe- sized that apoptosis is an important source of antigen in SLE [2]. They and others have demonstrated that the caspase enzymes involved in the destruction of the nucleus cleave certain well- known autoantigens (e.g. DNA-protein kinase, PARP, U1-RNP) revealing potentially autoreactive epitopes [3–5]. An important characteristic of apoptosis is the cleavage of chromatin into nucleo- somal units by an endonuclease (caspase-activated DNase (CAD)) which is activated by caspases [6]. On a DNA gel these nucleosomes produce a ‘ladder’ of oligomers composed of different numbers of nucleosomes [6]. Nucleosomes are composed of DNA wound around a histone core, which comprises four histone subunits, i.e. a tetramer of H3 and H4 make up the central unit, attached either side of which are dimers of H2A and H2B. Externally bound H1 molecules hold adjacent nucleosomes together.
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