Question 20 from the attending physician in the Department of Rheumatology and Immunology—What are antinucleosome antibodies?

Nucleosomes are subunits of the basic repetitive structure of eukaryotic chromatin and are very important for the composition of nuclear DNA. The nucleosome contains four core histones (histones) H2A, H2B, H3 and H4 that appear in pairs to form a histone octamer, surrounded by 146 double helix DNA base pairs for two weeks. A tetrameric complex composed of two H3 and H4 molecules respectively forms the interior of the nucleosome core particle. H2A-H2B dimers are located on the surface of nucleosomes. H1 occupies the top position of the nucleosome and is connected to adjacent nucleosomes by linking DNA. H1 is involved in the polymerization and dissociation of helical DNA. Recent studies have shown that nucleosomes are the main autoantigens of SLE and may be directly related to the pathogenesis and pathological changes of SLE. The excessive release of nucleosomes caused by abnormal cell apoptosis in SLE patients may be one of the main triggers of immune abnormalities in this disease. First, nucleosomes will become activators of polyclonal B cells, which may be related to the initial stage of SLE disease; but more importantly, nucleosomes are self-antigens recognized by pathogenic T helper cells in SLE, which not only cause Syngeneic B cells produce nucleosome-specific autoantibodies and lead to the formation of anti-DNA antibodies and anti-histone antibodies.

The clinical significance of anti-nucleosome antibodies: nucleosomes have been confirmed as the main autoantigen in SLE in recent years. The deposition of immune complexes in target organs and the massive activation of inflammatory mediators (including complement) are one of the basic mechanisms that cause systemic tissue inflammatory damage in SLE. Recent evidence suggests that, in addition to traditional pathogenic anti-double-stranded DNA antibodies and their antigen-antibody complexes, autoantibodies to nucleosomes and histone components and their antigen-antibody complexes may play a key role in the pathogenesis of SLE. , especially in the pathogenesis of glomerulonephritis (lupus kidney). The sensitivity of anti-nucleosome antibodies in the diagnosis of SLE is 58%-71%, and the specificity can reach 97%-99%. Anti-nucleosome antibodies are more common in active lupus, especially lupus nephritis, and may be specific antibodies for SLE. Simultaneous detection with other SLE-specific antibodies such as anti-double-stranded DNA antibodies, anti-DNP antibodies, and anti-Sm antibodies can significantly improve Sensitivity and specificity of clinical diagnosis of SLE.