Anti-histone antibodies
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Specificity
Anti-histone antibodies target five major classes of histone protein subunits: H1, H2A, H2B, H3, and H4. Anti-histone antibodies are diverse, so aside from targeting the protein subunits, different antibodies may also be specific for different complexes, including the H2A-H2B dimer or the H3-H4 tetramer. There is evidence that IgG and IgM anti-histone antibodies produced as a result of different drug exposures are specific to epitopes of different histone complexes. Highly modified histones have been shown to prompt a greater immune response.
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Detecting antibodies
Anti-histone antibodies can be clinically detected using an ELISA assay. A blood sample is required for the test.
Indirect immunofluorescence can also be used to detect anti-histone antibodies. Homogeneous, diffuse staining indicates the presence of anti-histone antibodies, chromatin, and some double-stranded DNA.
Implications in disease
Ninety-six percent of patients with lupus induced by procainamide will have a positive test for anti-histone antibodies, and 100% of patients whose lupus was induced by penicillamine, isoniazid, or methyldopa will have a positive test for anti-histone antibodies. In 70% of patients with rheumatoid arthritis, Felty's syndrome, Sjogren's syndrome, systemic sclerosis, and primary biliary cirrhosis, anti-histone antibodies are present. Anti-histone antibodies may also be present in Alzheimer's disease and dementia patients.
A value of greater than 1.5 units relative to a control serum is considered a positive ELISA test for the anti-histone antibodies. Patients with drug-induced lupus erythematosus typically have positive tests for anti-histone antibodies but do not have indications for anti-dsDNA antibodies. Patients with idiopathic systemic lupus erythematosus have both types of autoantibodies present in their blood. Thus, this test can be useful in distinguishing these two illnesses.