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Anti-histone antibodiesAnti-histone antibodies are autoantibodies that are a subset of the anti-nuclear antibody family, which specifically target histone protein subunits or histone complexes.[1] They were first reported by Henry Kunkel, H.R. Holman, and H.R.G. Dreicher in their studies of cellular causes of lupus erythematosus in 1959–60.[2][3] Today, anti-histone antibodies are still used as a marker for systemic lupus erythematosus, but are also implicated in other autoimmune diseases like Sjögren syndrome, dermatomyositis, or rheumatoid arthritis.[4][5] Anti-histone antibodies can be used as a marker for drug-induced lupus. Specificity Anti-histone antibodies target five major classes of histone protein subunits: H1, H2A, H2B, H3, and H4.[6] 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.[7] Highly modified histones have been shown to prompt a greater immune response.[8] Detecting antibodiesAnti-histone antibodies can be clinically detected using an ELISA assay. A blood sample is required for the test.[9][5] 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.[4] Implications in diseaseNinety-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.[6] 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.[9] References
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