Nucleosome

Anti-nucleosome antibodies (also referred to as anti-chromatin antibodies) constitute one of the first autoantibody specificities found to be present in systemic lupus erythematosus (SLE) having been detected as early as 1948 using the LE cell test. The prevalence of anti-nucleosome antibodies in SLE is of the order of 50-100%, and the nucleosome has been identified as the initiating and driving immunogen in SLE. Antinucleosome antibodies are now considered to be a more sensitive marker for SLE than anti-dsDNA antibodies and a high anti-nucleosome antibody titre has been reported to be indicative of lupus nephritis. 

Anti-nucleosome antibodies have been found (with a lower prevalence than in SLE) in a number of other autoimmune diseases such as systemic sclerosis, Sjögren's syndrome and mixed connective tissue disease and are also found in 40-50% of patients with autoimmune hepatitis type I. Anti-ribosomal P antibodies have also been reported to bind to nucleosomes.
 
The nucleosome is the basic structural subunit of chromatin, the native complex of histones and DNA found in the nucleus of eukaryotic cells. It is composed of about 200 base pairs of DNA wrapped twice around a (H2A-H2B-H3-H4) histone octamer with histone H1 bound on the periphery. 

Nucleosomes can be isolated by digesting the linker DNA holding them together in chromatin with micrococcal nuclease. The most effective form of nucleosomes for detecting patient autoantibodies are prepared in this way and stripped of H1 histone to yield a nucleosome core particle in which 146 base pairs of DNA are wrapped around an octamer of two H2A-H2B dimers that surround an H3-H4 tetramer.  Autoantibodies against subnucleosome particles occur in SLE, they are however less frequent.

 

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