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Anti-transglutaminase antibodies

anti-transglutaminase antibodies cpt code, anti-transglutaminase antibody test
Anti-transglutaminase antibodies ATA are autoantibodies against the transglutaminase protein Antibodies serve an important role in the immune system by detecting cells and substances that the rest of the immune system then eliminates These cells and substance can be foreign for example, viruses 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 diseases

ATA can be classified according to 2 different schemes: transglutaminase isoform and immunoglobulin reactivity subclass IgA, IgG toward transglutaminases


  • 1 Transglutaminase isoform reactivity
    • 11 Anti-tissue transglutaminase
    • 12 Anti-endomysial reactivity
    • 13 Anti-epidermal transglutaminase
  • 2 Immunoglobin subclass
  • 3 Associated Conditions
    • 31 Celiac Disease
    • 32 Inflammatory bowel disease
    • 33 Arthritis
    • 34 Type 1 Diabetes, previously known as Juvenile diabetes and anti-tTG
    • 35 Asymptomatic ATA+
    • 36 Symptomatic ATA+
    • 37 Alcohol consumption
  • 4 Mechanism of autoimmunity
  • 5 References
  • 6 External links

Transglutaminase isoform reactivity


Anti-tissue transglutaminase

Antibodies to tissue transglutaminase abbreviated as anti-tTG or anti-TG2 are found in patients with several conditions, including celiac disease, juvenile diabetes, inflammatory bowel disease, and various forms of arthritis

In celiac disease, ATA are involved in the destruction of the villous extracellular matrix and target the destruction of intestinal villous epithelial cells by killer cells Deposits of anti-tTG in the intestinal epithelium predict celiac disease

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 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

Anti-epidermal transglutaminase

Antibodies to epidermal transglutaminase eTG, also keratinocyte transglutaminase are the autoantibodies believed to cause dermatitis herpetiformis

Immunoglobin subclass

ATA IgA are more frequently found in Celiac Disease CD; however, ATA IgG 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, DQ25 is found in most CD, has genetic linkage to the IgA-less gene location

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

High levels titers of ATA are found in almost all instances of celiac disease 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


Studies of patients with various forms of arthritis 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 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-specific T-cells

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 of the hip
  • lower hemoglobin levels
  • decreased weight
  • lower cholesterol
  • higher blood glucose

Similar studies:

  • increased mortality, particularly to cancer

Symptomatic ATA+

  • greater impairment of neurophysiology peripheral neuropathies and motor neuron disease
  • increased inflammatory bowel symptoms not celiac or EMA

Alcohol consumption

ATA correlated with biomarkers of alcohol consumption, proinflammatory cytokines and markers of fibrogenesis

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-cells These T-helper cells then stimulate B-cells to multiply and mature into plasma cells 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, which includes wheat See Wheat taxonomy, barley, and rye The T-cells are defined by the ability to react to HLA-DQ8 and DQ25 restricted antigens and gliadin is one of the antigens Gliadin is a favored dietary substrate for transglutaminase because of many enzyme reaction sites on gliadin In disease, transglutaminase reacts with gliadin forming a linkage 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


  1. ^ Krause, I; Anaya, JM; Fraser, A; Barzilai, O; Ram, M; Abad, V; Arango, A; García, J; Shoenfeld, Y 2009 "Anti-infectious antibodies and autoimmune-associated autoantibodies in patients with type I diabetes mellitus and their close family members" Annals of the New York Academy of Sciences 1173: 633–9 doi:101111/j1749-6632200904619x PMID 19758209 
  2. ^ a b Farrace, MG; Picarelli, A; Di Tola, M; Sabbatella, L; Marchione, OP; Ippolito, G; Piacentini, M Jul 2001 "Presence of anti-"tissue" transglutaminase antibodies in inflammatory intestinal diseases: an apoptosis-associated event" Cell Death & Differentiation 8 7: 767–70 doi:101038/sjcdd4400880 PMID 11464221 Retrieved 26 December 2012 
  3. ^ Teichmann, Joachim; Voglau, Marcus J; Lange, Uwe 13 October 2009 "Antibodies to human tissue transglutaminase and alterations of vitamin D metabolism in ankylosing spondylitis and psoriatic arthritis" Rheumatology International 30 12: 1559–1563 doi:101007/s00296-009-1186-y PMID 19823832 
  4. ^ Picarelli, A; Di Tola, M; Sabbatella, L; Vetrano, S; Anania, MC; Spadaro, A; Sorgi, ML; Taccari, E Dec 2003 "Anti-tissue transglutaminase antibodies in arthritic patients: a disease-specific finding" Clinical Chemistry 49 12: 2091–4 doi:101373/clinchem2003023234 PMID 14633886 Retrieved 26 December 2012 
  5. ^ Kaukinen K, Peraaho M, Collin P, Partanen J, Woolley N, Kaartinen T, Nuuntinen T, Halttunen T, Maki M, Korponay-Szabo I 2005 "Small-bowel mucosal tranglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: A Prospective and radmonized clinical study" Scand J Gastroenterology 40 5: 564–572 doi:101080/00365520510023422 PMID 16036509 
  6. ^ Salmi T, Collin P, Korponay-Szabó I, Laurila K, Partanen J, Huhtala H, Király R, Lorand L, Reunala T, Mäki M, Kaukinen K 2006 "Endomysial antibody‐negative coeliac disease: clinical characteristics and intestinal autoantibody deposits" Gut 55 12: 1746–53 doi:101136/gut2005071514 PMC 1856451  PMID 16571636 
  7. ^ Pruessner HT March 1998 "Detecting celiac disease in your patients" Am Fam Physician 57 5: 1023–34, 1039–41 PMID 9518950 
  8. ^ Hull CM, Liddle M, Hansen N, et al May 2008 "Elevation of IgA anti-epidermal transglutaminase antibodies in dermatitis herpetiformis" Br J Dermatol 159 1: 120–4 doi:101111/j1365-2133200808629x PMID 18503599 
  9. ^ Donaldson MR, Firth SD, Wimpee H, et al 2007 "Correlation of duodenal histology with tissue transglutaminase and endomysial antibody levels in pediatric celiac disease" Clin Gastroenterol Hepatol 5 5: 567–73 doi:101016/jcgh200701003 PMID 17428743 
  10. ^ Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken E, Schuppan D 1997 "Identification of tissue transglutaminase as the autoantigen of celiac disease" Nat Med 3 7: 797–801 doi:101038/nm0797-797 PMID 9212111 
  11. ^ Roth EB, Stenberg P, Book C, Sjöberg K 2006 "Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumatoid arthritis--new pathways to epitope spreading" Clin Exp Rheumatol 24 1: 12–8 PMID 16539813 
  12. ^ Lampasona V, Bonfanti R, Bazzigaluppi E, Venerando A, Chiumello G, Bosi E, Bonifacio E 1999 "Antibodies to tissue transglutaminase C in type I diabetes" Diabetologia 42 10: 1195–1198 doi:101007/s001250051291 PMID 10525659 
  13. ^ Ludvigsson J, Ludvigsson J, Ekbom A, Montgomery S 2006 "Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents" Diabetes Care 29 11: 2483–8 doi:102337/dc06-0794 PMID 17065689 
  14. ^ Hansen D, Brock-Jacobsen B, Lund E, Bjørn C, Hansen L, Nielsen C, Fenger C, Lillevang S, Husby S 2006 "Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years' follow-up" Diabetes Care 29 11: 2452–6 doi:102337/dc06-0990 PMID 17065683 
  15. ^ Bao F, Yu L, Babu S, Wang T, Hoffenberg EJ, Rewers M, Eisenbarth GS 1999 "One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies" J Autoimmun 13 1: 143–148 doi:101006/jaut19990303 PMID 10441179 
  16. ^ West J, Logan RF, Hill PG, Khaw KT 2007 "The iceberg of celiac disease: what is below the waterline" Clin Gastroenterol Hepatol 5 1: 59–62 doi:101016/jcgh200610020 PMID 17234556 
  17. ^ Metzger MH, Heier M, Mäki M, et al 2006 "Mortality excess in individuals with elevated IgA anti-transglutaminase antibodies: the KORA/MONICA Augsburg cohort study 1989-1998" Eur J Epidemiol 21 5: 359–65 doi:101007/s10654-006-9002-4 PMID 16649072 
  18. ^ Matà S, Renzi D, Pinto F, Calabrò A 2006 "Anti-tissue transglutaminase IgA antibodies in peripheral neuropathy and motor neuronopathy" Acta Neurol Scand 114 1: 54–8 doi:101111/j1600-0404200600602x PMID 16774628 
  19. ^ Di Tola M, Sabbatella L, Anania MC, et al 2004 "Anti-tissue transglutaminase antibodies in inflammatory bowel disease: new evidence" Clin Chem Lab Med 42 10: 1092–7 doi:101515/CCLM2004225 PMID 15552265 
  20. ^ Koivisto H, Hietala J, Anttila P, Niemelä O 2007 "Co-Occurrence of IgA Antibodies Against Ethanol Metabolites and Tissue Transglutaminase in Alcohol Consumers: Correlation with Proinflammatory Cytokines and Markers of Fibrogenesis" Digestive Diseases and Sciences 53 2: 500–5 doi:101007/s10620-007-9874-5 PMID 17597408 
  21. ^ Fleckenstein B, Qiao SW, Larsen MR, Jung G, Roepstorff P, Sollid LM 2004 "Molecular characterization of covalent complexes between tissue transglutaminase and gliadin peptides" J Biol Chem 279 17: 17607–16 doi:101074/jbcM310198200 PMID 14747475 
  22. ^ Barone MV, Caputo I, Ribecco MT, et al 2007 "Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease" Gastroenterology 132 4: 1245–53 doi:101053/jgastro200701030 PMID 17408665 

External links

  • Anti-Tissue Transglutaminase tTG Antibodies Also Found in Inflammatory Bowel Disease
  • Tg6 Antibody Plays a Key Role in Celiac-Related Neurological Disorders Celiaccom 09/02/2008

anti-transglutaminase antibodies, anti-transglutaminase antibodies cpt code, anti-transglutaminase antibody test, anti-transglutaminase test

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Anti-transglutaminase antibodies

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