Anti-nucleosome antibodies

SARDs are a heterogeneous group of disorders characterized by dysregulation of the immune system, that starts to turn against the body’s own tissues. Major SARDs include systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and Sjögren’s syndrome. These diseases can affect multiple organs and share common symptoms such as fatigue, fever, joint pain and skin rash. Diagnosis relies on a combination of clinical assessment and specific autoantibody tests. Early diagnosis is crucial to initiate appropriate therapy and slow down disease progression.

Nucleosomes are the fundamental structural units of chromatin, consisting of approximately 147 base pairs of DNA wrapped around an octamer of histone proteins (H2A, H2B, H3, and H4). They form the first level of DNA compaction within the cell nucleus, serving as the basis for higher organisation levels up to the formation of chromosomes. Autoantibodies recognising this complex are known as anti-nucleosome antibodies (ANuA) and are a major diagnostic marker for systemic lupus erythematosus (SLE), with a reported sensitivity ranging from 56% to 90% and a high specificity. Compared to anti-dsDNA antibodies, anti-nucleosome antibodies may appear earlier in the disease course and can also be detected in up to 40% of patients who are anti-dsDNA negative.

These autoantibodies may also occur in drug-induced lupus and, less frequently, in other systemic autoimmune diseases. In patients with antiphospholipid syndrome (APS), co-positivity for anti-nucleosome antibodies has been associated with an increased risk of progression to SLE.

Serological detection of anti-nucleosome antibodies is therefore useful not only for a diagnosis but also for prognostic stratification and to monitor disease activity, particularly regarding renal involvement.