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Autoantibody

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An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies.

Production

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Antibodies are produced by B cells in two ways: (i) randomly, and (ii) in response to a foreign protein or substance within the body. Initially, one B cell produces one specific kind of antibody. In either case, the B cell is allowed to proliferate or is killed off through a process called clonal deletion. Normally, the immune system is able to recognize and ignore the body's own healthy proteins, cells, and tissues, and to not overreact to non-threatening substances in the environment, such as foods. Sometimes, the immune system ceases to recognize one or more of the body's normal constituents as "self", leading to production of pathological autoantibodies. Autoantibodies may also play a nonpathological role; for instance they may help the body to destroy cancers and to eliminate waste products. The role of autoantibodies in normal immune function is also a subject of scientific research.

Cause

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The causes of autoantibody production are varied and not well understood. It is thought that some autoantibody production is due to a genetic predisposition combined with an environmental trigger, such as a viral illness or a prolonged exposure to certain toxic chemicals. There is generally not a direct genetic link however. While families may be susceptible to autoimmune conditions, individual family members may have different autoimmune disorders, or may never develop an autoimmune condition. Researchers believe that there may also be a hormonal component as many of the autoimmune conditions are much more prevalent in women of childbearing age. While the initial event that leads to the production of autoantibodies is still unknown, there is a body of evidence that autoantibodies may have the capacity to maintain their production.[1][2]

Diseases

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Further information: Systemic autoimmune diseases

The type of autoimmune disorder or disease that occurs and the amount of destruction done to the body depends on which systems or organs are targeted by the autoantibodies, and how strongly. Disorders caused by organ specific autoantibodies, those that primarily target a single organ, (such as the thyroid in Graves' disease and Hashimoto's thyroiditis), are often the easiest to diagnose as they frequently present with organ related symptoms. Disorders due to systemic autoantibodies can be much more elusive. Although the associated autoimmune disorders are rare, the signs and symptoms they cause are relatively common. Symptoms may include: arthritis-type joint pain, fatigue, fever, rashes, cold or allergy-type symptoms, weight loss, and muscular weakness. Associated conditions include vasculitis which are inflammation of blood vessels and anemia. Even if they are due to a particular systemic autoimmune condition, the symptoms will vary from person to person, vary over time, vary with organ involvement, and they may taper off or flare unexpectedly. Add to this the fact that a person may have more than one autoantibody, and thus have more than one autoimmune disorder, and/or have an autoimmune disorder without a detectable level of an autoantibody, complicating making a diagnosis.

The diagnosis of disorders associated with systemic autoantibodies starts with a complete medical history and a thorough physical exam. Based on the patient's signs and symptoms, the doctor may request one or more diagnostic studies that will help to identify a specific disease. As a rule, information is required from multiple sources, rather than a single laboratory test to accurately diagnose disorders associated with systemic autoantibodies. Tests may include:

  • blood tests to detect inflammation, autoantibodies, and organ involvement
  • x-rays and other imaging scans to detect changes in bones, joints, and organs
  • biopsies to look for pathologic changes in tissue specimens

Indications for autoantibody tests

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Autoantibody tests may be ordered as part of an investigation of chronic progressive arthritis type symptoms and/or unexplained fevers, fatigue, muscle weakness and rashes. The antinuclear antibody (ANA) test is often ordered first. ANA is a marker of the autoimmune process – it is positive with a variety of different autoimmune diseases but not specific. Consequently, if an ANA test is positive, it is often followed up with other tests associated with arthritis and inflammation, such as a rheumatoid factor (RF), an erythrocyte sedimentation rate (ESR), a c-reactive protein (CRP), and/or complement protein|complement levels.

A single autoantibody test is not diagnostic, but may give clues as to whether a particular disorder is likely or unlikely to be present. Each autoantibody result should be considered individually and as part of the group. Some disorders, such as systemic lupus erythematosus (SLE) may be more likely if several autoantibodies are present, while others, such as mixed connective tissue disease (MCTD) may be more likely if a single autoantibody, ribonucleic protein (RNP), is the only one present. Those who have more than one autoimmune disorder may have several detectable autoantibodies.

Whether a particular autoantibody will be present is both very individual and a matter of statistics. Each will be present in a certain percentage of people who have a particular autoimmune disorder. For instance, up to 80% of those with SLE will have a positive double strand anti-double stranded DNA (anti-dsDNA) autoantibody test, but only about 25–30% will have a positive RNP. Some individuals who do have an autoimmune disorder will have negative autoantibody test results, but at a later date – as the disorder progresses - the autoantibodies may develop.

Systemic autoantibody tests are used to:

  • Help diagnose systemic autoimmune disorders.
  • Help determine the degree of organ or system involvement and damage (Along with other tests such as a complete blood count or comprehensive metabolic panel)
  • Monitor the course of the disorder and the effectiveness of treatments. There is no prevention or cure for autoimmune disorders at this time. Treatment is used to alleviate symptoms and to help maintain body function.
  • Monitor remissions, flares, and relapses

Antibody profiling

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Antibody profiling is used for identifying persons from forensic samples. The technology can uniquely identify a person by analyzing the antibodies in body fluids. A unique, individual set of antibodies, called individual specific autoantibodies (ISA), is found in blood, serum, saliva, urine, semen, perspiration, tears, and body tissues, and the antibodies are not affected by illness, medication, or food/drug intake. An unskilled technician using inexpensive equipment can complete a test in a couple of hours.[3]

List of some autoantibodies and commonly associated diseases

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Note: the sensitivity and specificity of various autoantibodies for a particular disease is different for different diseases.

Autoantibody Antibody target Condition
Antinuclear antibodies Anti-SSA/Ro autoantibodies ribonucleoproteins systemic lupus erythematosus, neonatal heart block, primary Sjögren syndrome
Anti-La/SS-B autoantibodies Primary Sjögren syndrome
Anti-centromere antibodies centromere CREST syndrome
Anti-dsDNA double-stranded DNA SLE
Anti-Jo1 histidine-tRNA ligase inflammatory myopathy
Anti-RNP Ribonucleoprotein Mixed connective tissue disease
Anti-Smith snRNP core proteins SLE
Anti-topoisomerase antibodies Type I topoisomerase systemic sclerosis (anti-Scl-70 antibodies)
Anti-histone antibodies histones SLE and drug-induced LE[4]
Anti-p62 antibodies[5] nucleoporin 62 primary biliary cirrhosis[5][6][7]
Anti-sp100 antibodies[6] Sp100 nuclear antigen
Anti-glycoprotein-210 antibodies[7] nucleoporin 210kDa
Anti-transglutaminase antibodies Anti-tTG celiac disease
Anti-eTG dermatitis herpetiformis
Anti-ganglioside antibodies ganglioside GQ1B Miller Fisher syndrome
ganglioside GD3 acute motor axonal neuropathy (AMAN)
ganglioside GM1 multifocal motor neuropathy with conduction block (MMN)
Anti-actin antibodies actin Coeliac disease (antibody levels correlate with the level of intestinal damage[8][9]), autoimmune hepatitis, gastric cancer
anti-CCP cyclic citrullinated peptide rheumatoid arthritis
Liver kidney microsomal type 1 antibody autoimmune hepatitis[10]
Lupus anticoagulant Anti-thrombin antibodies thrombin systemic lupus erythematosus
Antiphospholipid antibodies phospholipid antiphospholipid syndrome
Anti-neutrophil cytoplasmic antibody c-ANCA proteins in neutrophil cytoplasm granulomatosis with polyangiitis
p-ANCA neutrophil perinuclear microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, systemic vasculitides (non-specific)
Rheumatoid factor IgG rheumatoid arthritis
Anti-smooth muscle antibody smooth muscle chronic autoimmune hepatitis
Anti-mitochondrial antibody mitochondria primary biliary cirrhosis[11]
Anti-SRP signal recognition particle dermatomyositis[12]
exosome complex scleromyositis
Anti-AChR nicotinic acetylcholine receptor myasthenia gravis
Anti-MUSK Muscle-specific kinase (MUSK) myasthenia gravis
Anti-VGCC voltage-gated calcium channel (P/Q-type) Lambert–Eaton myasthenic syndrome
Anti-Vinculin vinculin small intestinal bacterial overgrowth
Anti-thyroid autoantibodies Anti-TPO antibodies Thyroid peroxidase (microsomal) Hashimoto's thyroiditis, Graves' disease
Anti-thyroglobulin antibodies (TgAbs) Thyroglobulin Hashimoto's thyroiditis
Anti-thyrotropin receptor antibodies (TRAbs) TSH receptor Graves' disease
Anti-Hu (ANNA-1) Neuronal nuclear proteins paraneoplastic cerebellar degeneration, limbic encephalitis, encephalomyelitis, subacute sensory neuronopathy, choreathetosis[13]
Anti-Yo Cerebellar Purkinje cells paraneoplastic cerebellar degeneration
Anti-Ma encephalomyelitis, limbic encephalitis
Anti-Ri (ANNA-2) Neuronal nuclear proteins opsoclonus myoclonus syndrome
Anti-Tr glutamate receptor paraneoplastic cerebellar syndrome
Anti-amphiphysin amphiphysin stiff person syndrome, paraneoplastic cerebellar degeneration
Anti-GAD Glutamate decarboxylase stiff person syndrome, diabetes mellitus type 1
Anti-VGKC voltage-gated potassium channel (VGKC) limbic encephalitis, Isaac's Syndrome (autoimmune neuromyotonia)
Anti-CRMP-5 Collapsin response mediator protein 5 optic neuropathy, chorea
basal ganglia neurons Sydenham's chorea, paediatric autoimmune neuropsychiatric disease associated with Streptococcus (PANDAS)
Anti-NMDAr N-methyl-D-aspartate receptor (NMDA) anti-NMDA receptor encephalitis
NMO antibody aquaporin-4 neuromyelitis optica (Devic's syndrome)
Anti-desmoglein (anti-desmosome) Dsg3 (Desmoglein 3) and sometimes Dsg1 Pemphigus vulgaris
Anti-hemidesmosome hemidesmosomes Bullous pemphigoid
Anti-glomerular basement membrane basement membrane in lungs and kidneys Goodpasture syndrome
Anti-parietal cell gastric parietal cells Pernicious anemia
Anti-intrinsic factor intrinsic factor Pernicious anemia
Anti-phospholipase A2 receptor phospholipase A2 receptor Membranous nephropathy

See also

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References

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  1. ^ Böhm I. Apoptosis: the link between autoantibodies and leuko-/lymphocytopenia in patients. Scand J Rheumatol 2004;33: 409 - 416
  2. ^ Böhm I. Disruption of the cytoskeleton after apoptosis induction by autoantibodies. Autoimmunity 2003;36: 183 - 189
  3. ^ https://inlportal.inl.gov/portal/server.pt/community/idaho_national_laboratory_biological_systems/352/molecular_forensics/2691 Antibody Sensors
  4. ^ Table 5-9 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition.
  5. ^ a b Wesierska-Gadek J, Hohenuer H, Hitchman E, Penner E (1996). "Autoantibodies against nucleoporin p62 constitute a novel marker of primary biliary cirrhosis". Gastroenterology. 110 (3): 840–7. doi:10.1053/gast.1996.v110.pm8608894. PMID 8608894.
  6. ^ a b Szostecki C, Guldner HH, Netter HJ, Will H (1990). "Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis". J. Immunol. 145 (12): 4338–47. doi:10.4049/jimmunol.145.12.4338. PMID 2258622. S2CID 43572051.
  7. ^ a b Itoh S, Ichida T, Yoshida T, et al. (1998). "Autoantibodies against a 210 kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis". J. Gastroenterol. Hepatol. 13 (3): 257–65. doi:10.1111/j.1440-1746.1998.01553.x. PMID 9570238. S2CID 73008610.
  8. ^ Pedreira S, Sugai E, Moreno ML, et al. (2005). "Significance of smooth muscle/anti-actin autoantibodies in celiac disease". Acta Gastroenterol. Latinoam. 35 (2): 83–93. PMID 16127984.
  9. ^ Carroccio A, Brusca I, Iacono G, et al. (2007). "IgA anti-actin antibodies ELISA in coeliac disease: A multicentre study". Digestive and Liver Disease. 39 (9): 818–23. doi:10.1016/j.dld.2007.06.004. hdl:10447/34417. PMID 17652043.
  10. ^ Kerkar N, Ma Y, Davies ET, Cheeseman P, Mieli-Vergani G, Vergani D (December 2002). "Detection of liver kidney microsomal type 1 antibody using molecularly based immunoassays". J. Clin. Pathol. 55 (12): 906–9. doi:10.1136/jcp.55.12.906. PMC 1769836. PMID 12461054.
  11. ^ Oertelt S, Rieger R, Selmi C, Invernizzi P, Ansari A, Coppel R, Podda M, Leung P, Gershwin M (2007). "A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis". Hepatology. 45 (3): 659–65. doi:10.1002/hep.21583. PMID 17326160. S2CID 19227989.
  12. ^ Kao, A. H.; Lacomis, D.; Lucas, M.; Fertig, N.; Oddis, C. V. (2004). "Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy". Arthritis & Rheumatism. 50 (1): 209–215. doi:10.1002/art.11484. PMID 14730618.
  13. ^ Ropper, Allan H.; Samuels, Martin A. (2009). Adams and Victor's Principles of Neurology (9th ed.). McGraw Hill. p. 656. ISBN 978-0-07-149992-7.
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