Issue: 2003 > August > review

Lupus nephritis: consequence of disturbed removal of apoptotic cells?

J.H.M. Berden


In the last decade it has become clear that systemic
lupus erythematosus (SLE) is an autoantigen driven T cell dependent autoimmune disease. The nucleosome has been identified as a major autoantigen. Nucleosomes are generated during apoptosis. Either an increased or delayed apoptosis or a reduced clearance of apoptotic cells (which are not mutually exclusive) leads to an increased exposure of (modified, more immunogenic) nucleosomes to the immune system. This generates the formation of nucleosome specific T cells and antinucleosome autoantibodies.
After complex formation of antinucleosome or anti-doublestranded (ds)DNA antibodies with nucleosomes, these autoantibodies are targeted to basement membranes, especially the glomerular basement membrane (GBM).
This nephritogenic potential is due to the binding of the
positively charged histone components of the nucleosome to the negatively charged heparan sulphate (HS) within the GBM. This incites glomerular inflammation.