Anti-histone antibodies are autoantibodies that are a subset of the

anti-nuclear antibody Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human prote ...

family, which specifically target

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...

protein subunits or histone complexes. They were first reported by Henry Kunkel, H.R. Holman, and H.R.G. Dreicher in their studies of cellular causes of

lupus erythematosus Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blo ...

in 1959–60. 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 Dermatomyositis (DM) is a long-term inflammatory disorder which affects skin and the muscles. Its symptoms are generally a skin rash and worsening muscle weakness over time. These may occur suddenly or develop over months. Other symptoms may inc ...

, or

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

. Anti-histone antibodies can be used as a marker for drug-induced lupus.

Specificity

Anti-histone antibodies target 5 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.

Detecting antibodies

Anti-histone antibodies can be clinically detected using an

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...

assay. A

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...

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 Procainamide (PCA) is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is classified by the Vaughan Williams classification system as class Ia; thus it is a sodium channel blocker of cardiomyocytes. In add ...

will have a positive test for anti-histone antibodies, and 100% of patients whose lupus was induced by

penicillamine Penicillamine, sold under the brand name of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease. It is also used for people with kidney stones who have high urine cystine levels, rheumatoid arthritis, ...

isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For la ...

, or

methyldopa Methyldopa, sold under the brand name Aldomet among others, is a medication used for high blood pressure. It is one of the preferred treatments for high blood pressure in pregnancy. For other types of high blood pressure including very high blo ...

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 Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

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 Anti-double stranded DNA (Anti-dsDNA) antibodies are a group of anti-nuclear antibodies (ANA) the target antigen of which is double stranded DNA. Blood tests such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are routinely p ...

. 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.

References

{{Autoantibodies Autoantibodies