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 caused by such autoantibodies.
Contents
- 1 Production
- 2 Cause
- 3 Diseases
- 4 Indications for autoantibody tests
- 5 Antibody profiling
- 6 List of some autoantibodies and commonly associated diseases
- 7 See also
- 8 References
- 9 External links
Production
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. These autoantibodies attack the body's own healthy cells, tissues, and/or organs, causing inflammation and damage. 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
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
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
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:
- 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
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
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's syndrome |
| Anti-La/SS-B autoantibodies |
Primary Sjögren's 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 anti-actin antibodies correlated with the level of intestinal damage [8][9] |
| 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 |
polymyositis[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-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) |
See also
- Anti-glutamate receptor antibodies
- Reference ranges for blood tests#Autoantibodies
- Paraneoplastic syndrome
References
- ^ Böhm I. Apoptosis: the link between autoantibodies and leuko-/lymphocytopenia in patients. Scand J Rheumatol 2004;33: 409 - 416
- ^ Böhm I. Disruption of the cytoskeleton after apoptosis induction by autoantibodies. Autoimmunity 2003;36: 183 - 189
- ^ https://inlportal.inl.gov/portal/server.pt/community/idaho_national_laboratory_biological_systems/352/molecular_forensics/2691 Antibody Sensors
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
External links
- Autoimmunity – an Introduction Industrial Learning Unit on Chemgaroo
- Autoimmunityblog - summaries of research articles + glossary terms
- Autoantibodies at the US National Library of Medicine Medical Subject Headings (MeSH)
- Detection of autoantibodies with self-assembling radiolabeled antigen tetramers (a protocol)
- Antibody Sensors
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Immunology: lymphocytic adaptive immune system and complement
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| Lymphoid |
| Antigens |
- Antigen presentation/Professional APCs: Dendritic cell
- Macrophage
- B cell
- Immunogen
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| Antibodies |
- Antibody
- Monoclonal antibodies
- Polyclonal antibodies
- Autoantibody
- Microantibody
- Polyclonal B cell response
- Allotype
- Isotype
- Idiotype
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Immunity vs.
tolerance |
- action: Immunity
- Autoimmunity
- Alloimmunity
- Allergy
- Hypersensitivity
- Inflammation
- Cross-reactivity
- inaction: Tolerance
- Central
- Peripheral
- Clonal anergy
- Clonal deletion
- Tolerance in pregnancy
- Immunodeficiency
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| Immunogenetics |
- Affinity maturation (Somatic hypermutation
- Clonal selection)
- V(D)J recombination
- Junctional diversity
- Immunoglobulin class switching
- MHC/HLA
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| Lymphocytes |
- Cellular (T cell)
- Humoral (B cell)
- NK cell
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| Substances |
- Cytokines
- Opsonin
- Cytolysin
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Medical test: Antibodies: autoantibodies
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| Anti-nuclear antibody |
- PBC:
- Anti-gp210
- Anti-p62
- Anti-sp100
- ENA:
- Anti-topoisomerase/Scl-70
- Anti-Jo1
- ENA4
- Anti-Sm
- Anti-nRNP
- Anti-Ro
- Anti-La
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| Anti-mitochondrial antibody |
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| Anti-cytoplasm antibody |
- Anti-neutrophil cytoplasmic
- Anti-smooth muscle
- Anti-TPO/Antimicrosomal
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| Cell membrane |
- Anti-ganglioside
- Anti-GBM
- Anti-glutamate
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| Extracellular |
- Anti-thrombin
- Lupus anticoagulant
- Coeliac disease:
- Anti-transglutaminase
- Anti-gliadin not autoantibody
- RA
- Rheumatoid factor/anti-IgG
- Anti-citrullinated peptide
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| Multiple locations |
- Anti-phospholipid
- Anti-apolipoprotein
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