Anti-transglutaminase antibodies
Autoantibody | |
---|---|
Anti-transglutaminase | |
Common autoantibody characteristics | |
Autoantibody class | IgA, IgG |
DQ2.5 | |
HLA associations | DQ8 |
DQ2.2/DQ7.5 | |
Associated T-Cell restrictions |
DQ/gliadin, DQ/deamidated-gliadin |
Triggering agent(s) |
Triticeae glutens (Prolamins and Glutelins) |
Isoform specific | |
autoantibody characteristics | |
Autoantigen Isoform |
Tissue transglutaminase |
Autoantigen Gene | TGM2 |
Affected Organ(s) | Intestine (small) |
Affected Tissue(s) | Villi |
Affected Cells(s) | Epithelial Cells |
Also Affected | Epithelial matrix |
Associated Disease(s) |
Celiac disease |
Triggering agent |
& Gastrointestinal viruses |
Autoantigen Isoform |
Epidermal transglutaminase |
Autoantigen Gene | TGM3 |
Affected Organ(s) | Skin |
Associated Disease(s) |
Dermatitis herpetiformis |
Anti-transglutaminase antibodies (ATA) are
ATA can be classified according to 2 different schemes: transglutaminase
Transglutaminase isoform reactivity
Anti-tissue transglutaminase
Antibodies to
In celiac disease, ATA are involved in the destruction of the villous
Anti-endomysial reactivity
The endomysium 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).[6] The antiendomysial antibody test is a histological assay for patient serum binding to esophageal tissue from primate. EmA are present in celiac disease. They do not cause any direct symptoms to muscles, but detection of EmA is useful in the diagnosis of the disease.[7]
Anti-epidermal transglutaminase
Antibodies to
Immunoglobin subclass
ATA
Associated conditions
Celiac disease
Most attention to anti-transglutaminase antibodies is given with respect to celiac disease. 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.[9]
High levels (titers) of ATA are found in almost all instances of celiac disease.[10] 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 inflammatory bowel disease, specifically in Crohn's disease and ulcerative colitis.[2]
Arthritis
Studies of patients with various forms of
Type 1 Diabetes, previously known as Juvenile diabetes and anti-tTG
Childhood (male)
Asymptomatic ATA+
A recent screening[16] of 7550 Britons found 87 undetected ATA+. In this study a 50% increase of ATA was associated with:
- lower bone mineral densityof the hip.
- lower hemoglobin levels
- decreased weight.
- lower cholesterol
- higher blood glucose
Similar studies:
- increased mortality, particularly to cancer[17]
Symptomatic ATA+
- greater impairment of motor neuron disease.[18]
- increased inflammatory bowel symptoms (not celiac or EMA).[19]
Alcohol consumption
ATA correlated with biomarkers of alcohol consumption, proinflammatory
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
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
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.[22]
References
- S2CID 11261222.
- ^ PMID 11464221.
- S2CID 28299599.
- PMID 14633886.
- S2CID 27068601.
- PMID 16571636.
- PMID 9518950. Archived from the originalon 2011-10-20. Retrieved 2010-08-03.
- S2CID 21374261.
- PMID 17428743.
- S2CID 20033968.
- PMID 16539813.
- PMID 10525659.
- PMID 17065689.
- PMID 17065683.
- PMID 10441179.
- PMID 17234556.
- S2CID 31438746.
- S2CID 32691295.
- S2CID 46066640.
- S2CID 27382605.
- PMID 14747475.
- PMID 17408665.