Anti-transglutaminase antibodies (ATA) are

autoantibodies 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. Pr ...

against the

transglutaminase Transglutaminases are enzymes that in nature primarily catalyze the formation of an isopeptide bond between γ-carboxamide groups ( -(C=O)NH2 ) of glutamine residue side chains and the ε-amino groups ( -NH2 ) of lysine residue side cha ...

protein.

Antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

serve an important role in the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

by detecting cells and substances that the rest of the immune system then eliminates. These cells and substances can be foreign (for example,

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

es) and also can be produced by the body (for example, cancer cells). Antibodies against the body's own products are called autoantibodies. Autoantibodies can sometimes errantly be directed against healthy portions of the organism, causing

autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

s. ATA can be classified according to 2 different schemes: transglutaminase

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

and

immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

reactivity subclass ( IgA,

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...

) toward transglutaminases.

Transglutaminase isoform reactivity

Anti-tissue transglutaminase

Antibodies to

tissue transglutaminase Tissue transglutaminase (abbreviated as tTG or TG2) is a 78-kDa, calcium-dependent enzyme () of the protein-glutamine γ-glutamyltransferases family (or simply transglutaminase family). Like other transglutaminases, it crosslinks proteins between ...

(abbreviated as anti-tTG or anti-TG2) are found in patients with several conditions, including

celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barl ...

juvenile diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...

, and various forms of

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

. In celiac disease, ATA are involved in the destruction of the villous

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

and target the destruction of intestinal villous

epithelial cell Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

s by

killer cell Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and repres ...

s. Deposits of anti-tTG in the intestinal

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

predict celiac disease.

Anti-endomysial reactivity

The

endomysium The endomysium, meaning ''within the muscle'', is a wispy layer of areolar connective tissue that ensheaths each individual Skeletal muscle#Skeletal muscle fibers, muscle fiber, or muscle cell. It also contains capillaries and nerves. It overlies ...

is a layer of connective tissue that ensheaths a muscle fiber. The endomysium contains a form of transglutaminase called "tissue transglutaminase" or "tTG" for short, and antibodies that bind to this form of transglutaminase are called endomysial autoantibodies (EmA). The antiendomysial antibody test is a histological assay for patient serum binding to esophageal tissue from primate. EmA are present in

. They do not cause any direct symptoms to muscles, but detection of EmA is useful in the diagnosis of the disease.

Anti-epidermal transglutaminase

Antibodies to

epidermal The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...

transglutaminase (eTG, also

keratinocyte transglutaminase Protein-glutamine gamma-glutamyltransferase K is a transglutaminase enzyme that in humans is encoded by the ''TGM1'' gene. Function Keratinocyte transglutaminase enzymes serve to specifically catalyze the development of the cornified cell enve ...

) are the

believed to cause

dermatitis herpetiformis Dermatitis herpetiformis (DH) is a chronic autoimmune blistering skin condition, characterised by intensely itchy blisters filled with a watery fluid. DH is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not k ...

Immunoglobin subclass

ATA IgA are more frequently found in Celiac Disease (CD); however, ATA

are found in CD and at higher levels when affected individual had the IgA-less phenotype. The IgA-less phenotype is more common in CD than the normal population; however, one

haplotype A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...

, DQ2.5 is found in most CD, has

genetic linkage Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separ ...

to the IgA-less

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

location.

Associated conditions

Celiac disease

Most attention to anti-transglutaminase antibodies is given with respect to

. A recent study of children published in 2007 demonstrated that the level of ATA in correlates with the scalar Marsh score for the disease in the same patient. High levels (

titer Titer (American English) or titre (British English) 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 positiv ...

s) of ATA are found in almost all instances of

. Given the association of ATA with celiac disease, and the prevalence of the latter, it is estimated that ~1% of the population have potentially pathogenic levels of ATA.

Inflammatory bowel disease

A study published in Nature in 2001 found high levels of anti-transglutaminase antibodies in

- specifically in

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...

and

ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and a ...

Arthritis

Studies of patients with various forms of

showed highly increased frequencies of antibodies against guinea pig transglutaminase, human recombinant transglutaminase and peptidylarginine deiminase type 4 (PAD4). This suggests a potential for crossreactive antibodies between anti-tTG and anti-PAD4.

Type 1 Diabetes, previously known as Juvenile diabetes and anti-tTG

Childhood (male)

type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...

(T1D) increases the risk for CD and vice versa and the early signs of celiac disease may precede T1D in many cases. A search for CD in juvenile diabetes patients revealed that a gluten-free diet resulted in some improvements. An elevated number of diabetes patients have ATA along with increased numbers of

gluten Gluten is a structural protein naturally found in certain cereal grains. Although "gluten" often only refers to wheat proteins, in medical literature it refers to the combination of prolamin and glutelin proteins naturally occurring in all grain ...

-specific

T-cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

Asymptomatic ATA+

A recent screening of 7550 Briton's found 87 undetected ATA+. In this study a 50% increase of ATA was associated with: * lower

bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optica ...

of the hip. * lower

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...

levels * decreased weight. * lower

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

* higher

blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...

Similar studies: * increased mortality, particularly to cancer

Symptomatic ATA+

* greater impairment of

neurophysiology Neurophysiology is a branch of physiology and neuroscience that studies nervous system function rather than nervous system architecture. This area aids in the diagnosis and monitoring of neurological diseases. Historically, it has been dominated b ...

(

peripheral neuropathies Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...

and

motor neuron disease Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

. * increased inflammatory bowel symptoms (not celiac or EMA).

Alcohol consumption

ATA correlated with biomarkers of alcohol consumption, proinflammatory

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

and markers of

fibrogenesis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

Mechanism of autoimmunity

The antibodies to tissue transglutaminase follow a complex pathway of generation. For most antigens, T-cells specific to those antigens develop; for autoimmunity, either autoreactive T-cells are not suppressed, or antigens escape the protective process. T-cells are stimulated by antigen, presented by MHC molecules (HLA in humans) on antigen-reactive

B-cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...

s. These T-helper cells then stimulate B-cells to multiply and mature into

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substan ...

s that make IgA and IgG to that protein. In the case of celiac disease, the current understanding is that tTG autoimmunity arises when T-cells are generated against wheat gliadin and similar gluten proteins made by a class of grasses called ''

Triticeae Triticeae is a botanical tribe within the subfamily Pooideae of grasses that includes genera with many domesticated species. Major crop genera found in this tribe include wheat (see wheat taxonomy), barley, and rye; crops in other genera includ ...

'', which includes wheat (See

Wheat taxonomy During 10,000 years of cultivation, numerous forms of wheat, many of them hybrids, have developed under a combination of artificial and natural selection. This diversity has led to much confusion in the naming of wheats. This article explains ho ...

barley Barley (''Hordeum vulgare''), a member of the grass family, is a major cereal grain grown in temperate climates globally. It was one of the first cultivated grains, particularly in Eurasia as early as 10,000 years ago. Globally 70% of barley pr ...

, and rye. The T-cells are defined by the ability to react to

HLA-DQ8 HLA-DQ8 (DQ8) is a human leukocyte antigen serotype within the HLA-DQ (DQ) serotype group. DQ8 is a split antigen of the DQ3 broad antigen. DQ8 is determined by the antibody recognition of β8 and this generally detects the gene product of DQ ...

and DQ2.5 restricted antigens and gliadin is one of the antigens. Gliadin is a favored dietary substrate for

because of many

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

reaction sites on gliadin. In disease, transglutaminase reacts with gliadin forming a

linkage Linkage may refer to: * ''Linkage'' (album), by J-pop singer Mami Kawada, released in 2010 *Linkage (graph theory), the maximum min-degree of any of its subgraphs *Linkage (horse), an American Thoroughbred racehorse * Linkage (hierarchical cluster ...

. In forming this bond transglutaminase becomes linked to T-cell epitopes on gliadin. B-cells with surface IgM that react to transglutaminase can present it with bound gliadin peptides to T-cells which stimulate B-cell maturation and proliferation to plasma cells making IgA or IgM. ATA changes the behavior of tTG. Some studies have revealed that antibodies increase the activity of tTG, instead of inhibiting activity as is commonly encountered with function-altering antibodies. A recent study has shown that ATA also modify and increase replication in intestinal epithelial Cells, by apparently interacting with cell-surface transglutaminase.

References

{{DEFAULTSORT:Anti-Transglutaminase Antibodies T Gluten sensitivity