Anti-nuclear antibodies (
ANAs, also known as
anti-nuclear factor or
ANF) are autoantibodies directed against contents of the
cell nucleusIn cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
.
They are present in higher than normal numbers in autoimmune disease. The ANA test measures the pattern and amount of autoantibody which can attack the body's tissues as if they were foreign material. Autoantibodies are present in low
titerA titer is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positive or negative. The titer corresponds to the highest dilution factor that still yields a positive...
s in the general population, but in about 5% of the population, their concentration is increased, and about half of this 5% have an
autoimmune diseaseAutoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
.
ANA test
One can check for the presence of ANAs in blood serum by means of a laboratory test. There are also additional tests that allow one to test for individual ANAs. The general ANA test is usually one of two types: indirect
immunofluorescenceImmunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
or
ELISAEnzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
. The indirect immunofluoresence is considered to be the more accurate of the two, but the ELISA version is gaining popularity because of its lower cost.
Associated diseases
The normal titer of ANA is 1:40 or less. Higher titers are indicative of an autoimmune disease. The presence of ANA is indicative of
lupus erythematosusLupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
(present in 80-90% of cases), though they also appear in some other auto-immune diseases such as
Sjögren's syndromeSjögren's syndrome , also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva....
(60%),
rheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
(30-40%),
autoimmune hepatitisAutoimmune Hepatitis is a disease of the liver that occurs when the body's immune system attacks cells of the liver. Anomalous presentation of human leukocyte antigen class II on the surface of hepatocytes, possibly due to genetic predisposition or acute liver infection, causes a cell-mediated...
,
sclerodermaSystemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
and
polymyositisPolymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:...
&
dermatomyositisDermatomyositis is a connective-tissue disease related to polymyositis and Bramaticosis that is characterized by inflammation of the muscles and the skin.- Causes :...
(30%), and various non-rheumatological conditions associated with tissue damage. Other conditions with high ANA titre include Addison disease,
Idiopathic thrombocytopenic purpuraIdiopathic thrombocytopenic purpura is the condition of having an abnormally low platelet count of no known cause . As most incidents of ITP appear to be related to the production of antibodies against platelets, immune thrombocytopenic purpura or immune thrombocytopenia are terms also used to...
(ITP), Hashimoto's,
Autoimmune hemolytic anemiaAutoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
, Type I diabetes mellitus, Mixed connective tissue disorder.
Sensitivity
The following table list the
sensitivitySensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
of different types of ANAs for different diseases, in this case what percentage of those with the disease have the ANA. Some ANAs appear in several types of disease, resulting in lower
specificitySensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
of the test.
| ANA type | | Target antigen | | Sensitivity Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
|
| SLE Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
| Drug-induced LE 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 SLE...
| Diffuse systemic sclerosis | Limited systemic scleroderma The limited cutaneous form of systemic scleroderma is often referred to as CREST syndrome. "CREST" is an acronym for the five main features:* Calcinosis* Raynaud's syndrome* Esophageal dysmotility* Sclerodactyly* Telangiectasia...
| Sjögren syndrome | Inflammatory myopathy Inflammatory myopathy is a form of myopathy that involves inflammation of the muscle.Inflammatory myopathy is generally synonymous to the term dermatopolymyositis, which, according to ICD-10 encompasses three related diseases: polymyositis, dermatomyositis, and inclusion-body...
|
MCTD In medicine, mixed connective tissue disease , commonly abbreviated as MCTD, is an autoimmune disease, in which the body's defense system attacks itself. It was characterized in 1972....
|
All ANAs
(by indirect IFImmunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
) |
Various |
>95 |
>95 |
70-90 |
70-90 |
50-80 |
40-60 |
95 |
| Anti-dsDNA |
DNA |
40-60 |
- |
- |
- |
- |
- |
- |
| Anti-Sm |
Core proteins of snRNP snRNPs , or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs...
s |
20-30 |
- |
- |
- |
- |
- |
- |
| Anti-histone Anti-histone antibodies are autoantibodies that are found in 50%-70% of patients with systemic lupus erythematosus and in more than 95% of patients with drug-induced lupus erythematosus...
|
HistoneIn biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
s |
50-70 |
90 - 95 |
- |
- |
- |
- |
- |
| Anti Scl-70 |
Type I topoisomeraseType I topoisomerases cut one strand of double-stranded DNA, relax the strand, and reanneal the strands. They are further subdivided into two structurally and mechanistically distinct topoisomerases: type IA and type IB....
|
- |
- |
28-70 |
10-18 |
- |
- |
- |
| Anti-centromere |
Centromeric A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come closest in contact. It is involved in cell division as the point of mitotic spindle attachment...
proteins |
- |
- |
22-26 |
90 |
- |
- |
- |
| Anti-snRNP70 |
snRNP70 |
30-40 |
- |
15 |
10 |
- |
15 |
90 |
| SS-A (Ro) |
RNP Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
s |
30-50 |
- |
- |
- |
70-95 |
10 |
- |
| SS-B (La) |
RNP Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
s |
10-15 |
- |
- |
- |
60-90 |
- |
- |
| Jo-1 |
Histidine-tRNA ligase In enzymology, a histidine-tRNA ligase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are ATP, L-histidine, and tRNA, whereas its 3 products are AMP, diphosphate, and L-histidyl-tRNA....
|
- |
- |
- |
- |
- |
25 |
- |
- = less than 5% sensitivity
Unless else specified in boxes, then ref is: |
ANA classification
Following detection of a high titer of ANAs (e.g. 1:160), various subtypes are determined. This is typically done on cells of the
HEp-2 cell line. Examples include
- Anti-ENA (Extractable nuclear antigen)
- Anti-Ro (SS-A)
- Anti-La (SS-B)
- Anti-Sm (Smith antigen)
- Anti-nRNP
Anti-nRNP is a type of antibody.They are autoantibodies against some ribonucleoproteins.One form of Anti-nRNP is antibodies towards snRNP70 . Anti-snRNP70 antibodies can be elevated in mixed connective tissue disease....
(nuclear ribonucleoproteins)
- Anti Scl-70 (topoisomerase I)
- Anti-Jo
- Anti-gp-210
Anti-glycoprotein-210 antibodies are directed at gp210 and are found within primary biliary cirrhosis patients in high frequency. AGPA recognize the cytoplasmic oriented carboxyl terminus of the protein...
(nuclear pore gp-210)
- Anti-p62
Anti-p62 antibodies are found in a primary biliary cirrhosis. p62 is also more frequent in Stage IV primary biliary cirrhosis and is prognostic for severe disease. The autoantigen is the nucleoporin 62kDA protein....
(Nucleoporin 62Nucleoporin p62 is a protein complex associated with the nuclear envelope. The p62 protein remains associated with the nuclear pore complex-lamina fraction. p62 is synthesized as a soluble cytoplasmic precursor of 61 kDa followed by modification that involve addition of N-acetylglucosamine residues...
)
- Anti-dsDNA (double-stranded DNA)
- Anti-centromere
Anti-centromere antibodies occur in auto immune disorders; frequently in limited systemic scleroderma, , and, occasionally are found in the diffuse form of scleroderma...
History
The
LE cellAn LE cell is a neutrophil or macrophage that has phagocytized the denatured nuclear material of another cell. The denatured material is seen as an LE body....
was discovered in
bone marrowBone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
in 1948 by Hargraves
et al. This was the first indication that processes affecting the cell nucleus were responsible for
lupus erythematosusLupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
(LE). In the 1950s, progressively more sensitive and specific ANA serology tests became available.
External links