Autoantibody

From Wikipedia, the free encyclopedia - View original article

 
Jump to: navigation, search

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

Production[edit]

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, however, the immune system ceases to recognize one or more of the body's normal constituents as "self," leading to production of pathological autoantibodies. These autoantibodies attack the body's own healthy cells, tissues, and/or organs, causing inflammation and damage. It should be noted that 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[edit]

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.

Diseases[edit]

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:

Indications for autoantibody tests[edit]

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 SLE may be more likely if several autoantibodies are present, while others, such as MCTD (mixed connective tissue disease) may be more likely if a single autoantibody, RNP - ribonucleic protein 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-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:

Antibody Profiling[edit]

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.[1]

List of some autoantibodies and commonly associated diseases[edit]

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

Autoantibodyvs.Condition
Antinuclear antibodiesAnti-SSA/Ro autoantibodiesribonucleoproteinssystemic lupus erythematosus, neonatal heart block, primary Sjögren's syndrome
Anti-La/SS-B autoantibodiesPrimary Sjögren's syndrome
Anti-centromere antibodiescentromereCREST syndrome
Anti-neuronal nuclear antibody-2Riopsoclonus
Anti-dsDNAdouble-stranded DNASLE
Anti-Jo1histidine-tRNA ligaseinflammatory myopathy
Anti-RNPRibonucleoproteinMixed Connective Tissue Disease
Anti-SmithsnRNP core proteinsSLE
Anti-topoisomerase antibodiesType I topoisomerasesystemic sclerosis (anti-Scl-70 antibodies)
Anti-histone antibodieshistonesSLE and Drug-induced LE[2]
Anti-p62 antibodies[3]nucleoporin 62primary biliary cirrhosis[3][4][5]
Anti-sp100 antibodies [4]Sp100 nuclear antigen
Anti-glycoprotein-210 antibodies[5]nucleoporin 210kDa
Anti-transglutaminase antibodiesAnti-tTGceliac disease
Anti-eTGdermatitis herpetiformis
Anti-ganglioside antibodiesganglioside GQ1BMiller-Fisher Syndrome
ganglioside GD3acute motor axonal neuropathy (AMAN)
ganglioside GM1multifocal motor neuropathy with conduction block (MMN)
Anti-actin antibodiesactincoeliac disease anti-actin antibodies correlated with the level of intestinal damage [6][7]
anti-CCPcyclic citrullinated proteinrheumatoid arthritis
Liver kidney microsomal type 1 antibodyautoimmune hepatitis.[8]
Lupus anticoagulantAnti-thrombin antibodiesthrombinsystemic lupus erythematosus
phospholipidantiphospholipid syndrome
Anti-neutrophil cytoplasmic antibodyc-ANCAproteins in neutrophil cytoplasmWegener's granulomatosis
p-ANCAneutrophil perinuclearmicroscopic polyangiitis, Churg-Strauss syndrome, systemic vasculitides (non-specific)
Rheumatoid factorIgGRheumatoid arthritis
Anti-smooth muscle antibodysmooth musclechronic autoimmune hepatitis
Anti-mitochondrial antibodymitochondriaprimary biliary cirrhosis[9]
Anti-SRPsignal recognition particlepolymyositis[10]
exosome complexscleromyositis
nicotinic acetylcholine receptormyasthenia gravis
muscle-specific kinase (MUSK)myasthenia gravis
Anti-VGCCvoltage-gated calcium channel (P/Q-type)Lambert-Eaton myasthenic syndrome
thyroid peroxidase (microsomal)Hashimoto's thyroiditis
TSH receptorGraves' disease
Hu[disambiguation needed]paraneoplastic cerebellar syndrome
Yo (cerebellar Purkinje Cells)paraneoplastic cerebellar syndrome
amphiphysinStiff person syndrome, paraneoplastic cerebellar syndrome
Anti-VGKCvoltage-gated potassium channel (VGKC)limbic encephalitis, Isaac's Syndrome (autoimmune neuromyotonia)
basal ganglia neuronsSydenham's chorea, paediatric autoimmune neuropsychiatric disease associated with Streptococcus (PANDAS)
N-methyl-D-aspartate receptor (NMDA)encephalitis
glutamic acid decarboxylase (GAD)diabetes mellitus type 1, stiff person syndrome
aquaporin-4neuromyelitis optica (Devic's syndrome)

See also[edit]

References[edit]

  1. ^ https://inlportal.inl.gov/portal/server.pt/community/idaho_national_laboratory_biological_systems/352/molecular_forensics/2691 Antibody Sensors
  2. ^ Table 5-9 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7.  8th edition.
  3. ^ 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. 
  4. ^ 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. PMID 2258622. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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 . PMID 17652043. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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.  edit

External links[edit]