Anti-histone antibodies

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Anti-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.

Contents

Specificity

Histones are complexes of proteins, around which DNA is stored. Anti-histone antibodies may target the histone complex or any of the protein subunits shown here. Nucleosome structure-2.png
Histones are complexes of proteins, around which DNA is stored. Anti-histone antibodies may target the histone complex or any of the protein subunits shown here.

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 antibodies

Anti-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 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. [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]

Related Research Articles

<span class="mw-page-title-main">Sjögren syndrome</span> Medical condition

Sjögren syndrome or Sjögren's syndrome is a long-term autoimmune disease that affects the body's moisture-producing glands, and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system.

<span class="mw-page-title-main">Autoimmunity</span> Immune response against an organisms own healthy cells

In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, post-infectious IBS, diabetes mellitus type 1, Henoch–Schönlein purpura (HSP) sarcoidosis, systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM), and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.

<span class="mw-page-title-main">Antiphospholipid syndrome</span> Medical condition

Antiphospholipid syndrome, or antiphospholipid antibody syndrome, is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia. Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease. The diagnostic criteria require one clinical event and two positive blood test results spaced at least three months apart that detect lupus anticoagulant, anti-apolipoprotein antibodies, or anti-cardiolipin antibodies.

<span class="mw-page-title-main">Antinuclear antibody</span> Autoantibody that binds to contents of the cell nucleus

Antinuclear antibodies 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 proteins (autoantigens). In some cases, antibodies to human antigens are produced.

An autoantibody is an antibody produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases are associated with such antibodies.

Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs. AIHA is a relatively rare condition, with an incidence of 5–10 cases per 1 million persons per year in the warm-antibody type and 0.45 to 1.9 cases per 1 million persons per year in the cold antibody type. Autoimmune hemolysis might be a precursor of later onset systemic lupus erythematosus.

<span class="mw-page-title-main">Anti-mitochondrial antibody</span>

Anti-mitochondrial antibodies (AMA) are autoantibodies, consisting of immunoglobulins formed against mitochondria, primarily the mitochondria in cells of the liver.

Extractable nuclear antigens (ENAs) are over 100 different soluble cytoplasmic and nuclear antigens. They are known as "extractable" because they can be removed from cell nuclei using saline and represent six main proteins: Ro, La, Sm, RNP, Scl-70, Jo1. Most ENAs are part of spliceosomes or nucleosomes complexes and are a type of small nuclear ribonucleoprotein (snRNPS). The location in the nucleus and association with spliceosomes or nucleosomes results in these ENAs being associated with additional RNA and proteins such as polymerases. This quality of ENAs often makes it difficult to purify and quantify their presence for clinical use.

<span class="mw-page-title-main">Drug-induced lupus erythematosus</span> Medical condition

Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response producing symptoms similar to those of systemic lupus erythematosus (SLE). There are 38 known medications to cause DIL but there are three that report the highest number of cases: hydralazine, procainamide, and quinidine. While the criteria for diagnosing DIL has not been thoroughly established, symptoms of DIL typically present as muscle pain and joint pain. Generally, the symptoms recede after discontinuing use of the drugs.

<span class="mw-page-title-main">Belimumab</span>

Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States and Canada, and the European Union to treat systemic lupus erythematosus and lupus nephritis.

<span class="mw-page-title-main">Anti-centromere antibodies</span> Type of autoantibody

Anti-centromere antibodies are autoantibodies specific to centromere and kinetochore function. They occur in some autoimmune diseases, frequently in limited systemic scleroderma, and occasionally in the diffuse form of scleroderma. They are rare in other rheumatic conditions and in healthy persons.

Anti-glutamate receptor antibodies are autoantibodies detected in serum and/or cerebrospinal fluid samples of a variety of disorders such as encephalitis, epilepsy and ataxia. Clinical and experimental studies starting around the year 2000 suggest that these antibodies are not simply epiphenomena and are involved in autoimmune disease pathogenesis.

Anti-topoisomerase antibodies (ATA) are autoantibodies directed against topoisomerase and found in several diseases, most importantly scleroderma. Diseases with ATA are autoimmune disease because they react with self-proteins. They are also referred to as anti-DNA topoisomerase I antibody.

<span class="mw-page-title-main">Interferon alpha-1</span> Protein-coding gene in the species Homo sapiens

Interferon alpha-1 is a protein that in humans is encoded by the IFNA1 gene.

<span class="mw-page-title-main">Lupus erythematosus</span> Human disease

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, blood cells, heart, and lungs. The most common and most severe form is systemic lupus erythematosus.

<span class="mw-page-title-main">Anti-dsDNA antibodies</span> Group of anti-nuclear 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 performed to detect anti-dsDNA antibodies in diagnostic laboratories. They are highly diagnostic of systemic lupus erythematosus (SLE) and are implicated in the pathogenesis of lupus nephritis.

<span class="mw-page-title-main">Lupus</span> Human autoimmune disease

Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission during which there are few symptoms.

<span class="mw-page-title-main">Anti-SSA/Ro autoantibodies</span> Type of anti-nuclear autoantibodies

Anti-SSA autoantibodies are a type of anti-nuclear autoantibodies that are associated with many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, subacute cutaneous lupus erythematosus (SCLE), neonatal lupus and primary biliary cirrhosis. They are often present in Sjögren's syndrome (SS). Additionally, Anti-Ro/SSA can be found in other autoimmune diseases such as systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), rheumatoid arthritis (RA), and mixed connective tissue disease (MCTD), and are also associated with heart arrhythmia.

Blisibimod is a selective antagonist of B-cell activating factor, being developed by Anthera Pharmaceuticals as a treatment for systemic lupus erythematosus. It is currently under active investigation in clinical trials.

Ianalumab is a monoclonal antibody that is being investigated for autoimmune hepatitis, multiple sclerosis, pemphigus vulgaris, rheumatoid arthritis, Sjögren syndrome, and systemic lupus erythematosus.

References

  1. ↑ Muller, Sylviane (2014). Chapter 23 - Histone Autoantibodies, In Autoantibodies (Third ed.). San Diego, CA. p. 195. doi:10.1016/B978-0-444-56378-1.00023-X. ISBN   9780444563781.{{cite book}}: CS1 maint: location missing publisher (link)
  2. ↑ Holman, Henry R.; Deicher, H.R.G.; Kunkel, H.G. (July 1959). "The L.E. Cell and L.E. Serum Factors". Bulletin of the New York Academy of Medicine. 35 (7): 409–418. PMC   1806184 . PMID   13662729.
  3. ↑ Holman, H.R.; Deicher, H.R.G.; Kunkel, H.G. (January 1, 1960). Chapter 20. Multiple "Autoantibodies" to Cell Constituents in Systematic Lupus Erythematosus. In: Ciba Foundation Symposium - Cellular Aspects of Immunity. Chichester, UK: John Wiley & Sons. pp. 429–449. doi:10.1002/9780470719169.ch20.
  4. 1 2 Kumar, Vinay; Abbas, Abul; Aster, Jon (2018). Robbins Basic Pathology (10 ed.). Philadelphia, PA: Elsevier. pp. 150–157. ISBN   978-0-323-35317-5.
  5. 1 2 Inova Diagnostics. "Quanta Lite Histone". Inova Diagnostics a Werfen Company. Retrieved 8 February 2018.
  6. 1 2 Cozzani, Emanuele; Drosera, Massimo; Gasparini, Giulla; Parodi, Aurora (6 February 2014). "Serology of Lupus Erythematosus: Correlation between Immunopathological Features and Clinical Aspects". Autoimmune Diseases. 2014: 321359. doi: 10.1155/2014/321359 . PMC   3932647 . PMID   24649358.
  7. ↑ Burlingame, Rufus; Rubin, Robert (August 1991). "Drug-induced anti-histone autoantibodies display two patterns of reactivity with substructures of chromatin". Journal of Clinical Investigation. 88 (2): 680–690. doi:10.1172/JCI115353. PMC   295413 . PMID   1864977.
  8. ↑ Dema, Barbara; Charles, Nicolas (4 January 2016). "Autoantibodies in SLE: Specificities, Isotypes, and Receptors". Antibodies. 1 (5): 2. doi: 10.3390/antib5010002 . PMC   6698872 . PMID   31557984.
  9. 1 2 "HIS - Clinical: Histone Autoantibodies, Serum". Mayo Medical Laboratories. Retrieved 2018-08-04.
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