Celiac disease is a complex autoimmune disease which is characterized by a strong genetic association (HLA-DQ2 or -DQ8), gluten as nutritional etiological factor, and the enzyme tissue transglutaminase as endomysial autoantigen. Patients develop highly predictive IgA autoantibodies to tTG. Certain gluten peptides are presented by the disease-associated HLA-DQ2/DQ8 molecules leading to stimulation of gluten-specific T cells. This immune response which is driven in the lamina propria causes the mucosal transformation characteristic for celiac disease. Increased intestinal expression of tTG in patients with CD appears to play an important role in the pathogenesis of CD. Thus, modification of gluten peptides by tTG, especially deamidation of certain glutamine residues, can enhance their binding to HLA-DQ2 or -DQ8 and potentiate T cell stimulation. Furthermore, tTG-catalyzed cross-linking and consequent haptenization of gluten with extracellular matrix proteins allows for storage and extended availability of gluten in the mucosa. New therapeutic approaches aim at proteolytic destruction of immunodominant gliadin peptides that are resistant to intestinal enzymes by bacterial prolyl endopeptidases, the inhibition of tTG activity with highly specific enzyme inhibitors or at HLA-DQ2/DQ8 blocking peptide analogues.

Marsh MN: Gluten, major histocompatibility complex, and the small intestine: A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology 1992;102:330–354.
Trier JS: Celiac sprue. N Engl J Med 1991;325:1709–1719.
Oberhuber G, Granditsch G, Vogelsang H: The histopathology of coeliac disease: Time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol 1999;11:1185–1194.
George EK, Mearin ML, Van der Velde EA, Houwen RHJ, Bouquet J, Gijsbers CFM, Vandenbroucke JP: Low incidence of childhood celiac disease in the Netherlands. Pediatr Res 1995;37:213–218.
Talley NJ, Valdovinos M, Petterson TM, Carpenter HA, Melton LJ: Epidemiology of celiac sprue: A community-based study. Am J Gastroenterol 1994;89:843–846.
Fasano A, Catassi C: Current approaches to diagnosis and treatment of celiac disease: An evolving spectrum. Gastroenterology 2001;120:636–651.
Mäki M, Mustalahti K, Kokkonen J, Kulmala P, Haapalahti M, Karttunen T, Ilonen J, Laurila K, Dahlbom I, Hansson T, Höpfl P, Knip M: Prevalence of celiac disease among children in Finland. N Engl J Med 2003;348:2517–2524.
Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PH, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K: Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: A large multicenter study. Arch Intern Med 2003;163:286–292.
Mäki M, Collin P: Coeliac disease. Lancet 1997;349:1755–1759.
Trier JS: Diagnosis of celiac sprue. Gastroenterology 1998;115:211–216.
Book L, Zone JJ, Neuhausen SL: Prevalence of celiac disease among relatives of sib pairs with celiac disease in US families. Am J Gastroenterol 2003 Feb;98:377–381.
Hervonen K, Hakanen M, Kaukinen K, Collin P, Reunala T: First-degree relatives are frequently affected in coeliac disease and dermatitis herpetiformis. Scand J Gastroenterol 2002;37:51–55.
Greco L, Romino R, Coto I, Di Cosmo N, Percopo S, Maglio M, Paparo F, Gasperi V, Limongelli MG, Cotichini R, D’Agate C, Tinto N, Sacchetti L, Tosi R, Stazi MA: The first large population-based twin study of coeliac disease. Gut 2002;50:624–628.
Howell MD, Austin RK, Kelleher D, Nepom GT, Kagnoff MF: An HLA-D region restriction length polymorphism associated with celiac disease. J Exp Med 1986;164:333–339.
Sollid LM, Markussen G, Ek J, Gjerde H, Vartdal F, Thorsby E: Evidence for a primary association of celiac disease to a particular HLA-DQ α/β heterodimer. J Exp Med 1989;169:345–350.
Sollid LM, Thorsby E: HLA susceptibility genes in celiac disease: Genetic mapping and role in pathogenesis. Gastroenterology 1993;105:910–922.
Kagnoff MF: Understanding the molecular basis of coeliac disease. Gut 1990;31:497–499.
Houlston RS, Tomlinson IPM, Ford D, Seal S, Marossy AM, Ferguson A, Holmes GKT, Hosie KB, Howdle PD, Jewell DP, Godkin A, Kerr GD, Kumar P, Logan RFA, Love AHG, Johnston S, Marsh MN, Mitton S, O’Donoghue D, Roberts A, Walker-Smith JA, Stratton MF: Linkage analysis of candidate regions for celiac disease genes. Hum Mol Genet 1997;6:1335–1339.
Greco L, Babron MC, Corazza GR, Percopo S, Sica R, Clot F, Fulchignoni-Lataud MC, Zavattari P, Momigliano-Richiardi P, Casari G, Gasparini P, Tosi R, Mantovani V, De Virgiliis S, Iacono G, D’Alfonso A, Selinger-Leneman H, Lemainque A, Serre JL, Clerget-Darpoux F: Existence of a genetic risk factor on chromosome 5q in Italian coeliac disease families. Ann Hum Genet 2001;65:35–41.
Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D: Identification of tissue transglutaminase as the autoantigen of celiac disease. Nature Med 1997;3:797–801.
Dieterich W, Laag E, Schöpper H, Volta U, Ferguson A, Gillett H, Riecken EO, Schuppan D: Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998;115:1317–1321.
Sulkanen S, Halttunen T, Laurila K, Kolho KL, Korponay-Szabó IR, Sarnesto A, Savilahti E, Collin P, Mäki M: Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 1998;115:1322–1328.
Brusco G, Izzi L, Corazza GR: Tissue transglutaminase antibodies for coeliac disease screening. Ital J Gastroenterol Hapatol 1998;30:496–497.
Trevisiol C, Ventura A, Baldas V, Tommasini A, Santon D, Martelossi S, Torre G, Berti I, SpanÒ A, Crovella S, Amoroso A, Sblattero D, Marzari R, Bradbury A, Not T: A reliable screening procedure for coeliac disease in clinical practice. Scand J Gastroenterol 2002;37:679–684.
Bürgin-Wolff A, Dahlbom I, Hadziselimovic F, Petersson CJ: Antibodies against human tissue transglutaminase and endomysium in diagnosing and monitoring coeliac disease. Scand J Gastroenterol 2002;37:685–691.
Ventura A, Magazzù G, Greco L, for the SIGEP study group for autoimmune disorders in celiac disease: Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. Gastroenterology 1999;117:297–303.
Sategna Guidetti C, Solerio E, Scaglione N, Aimo G, Mengozzi G: Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders. Gut 2001;49:502–505.
Petaros P, Martelossi S, Tommasini A, Torre G, Caradonna M, Ventura A: Prevalence of autoimmune disorders in relatives of patients with celiac disease. Dig Dis Sci 2000;47:1427–1431.
Cronin CC, Shanahan F: Insulin-dependent diabetes mellitus and coeliac disease. Lancet 1997;349:1096–1097.
Schuppan D, Hahn EG: Celiac disease and its link to type 1 diabetes mellitus. J Ped Endocrinol Metab 2001;14:597–605.
Reunala T, Collin P: Diseases associated with dermatitis herpetiformis. Br J Dermatol 1997;136:315–318.
Sárdy M, Kárpáti S, Merkl B, Paulsson M, Smyth N: Epidermal transglutaminase (Tgase 3) is the autoantigen of dermatitis herpetiformis. J Exp Med 2002;195:747–757.
Van de Kamer JH, Weijers HA, Dicke WK: Coeliac disease IV: An investigation into the injurious constituents of wheat in connection with coeliac disease. Acta Paediatr 1953:42:223–231.
Kagnoff MF: Celiac disease; in Yamada T (ed): Testbook of Gastroenterology. Philadelphia, Lippincott, 1995, pp 1643–1661.
Wieser H: Chemistry of gliadins. Eur J Gastroenterol Hepatol 1991;3:102–107.
Sturgess R, Day P, Ellis HJ, Lundin KEA, Gjertsen HA, Kontakou M, Ciclitira PJ: Wheat peptide challenge in coeliac disease. Lancet 1994;343:758–761.
Mantzaris G, Jewell DP: In vivo toxicity of a synthetic dodecapeptide from A gliadin in patients with coeliac disease. Scand J Gastroenterol 1991;26:392–398.
De Ritis G, Auricchio S, Jones HW, Lew EJL, Bernardin JE, Kasarda DD: In vitro (organ culture) studies of the toxicity of specific A-gliadin peptides in celiac disease. Gastroenterology 1988;94:41–49.
Howdle PD, Ciclitira PJ, Simpson FG, Losowsky MS: Are all gliadins toxic in coeliac disease? An in vitro study of alpha, beta, gamma, and ω gliadins. Scand J Gastroenterol 1984;19:41–47.
Ciclitira PJ, Evans DJ, Fagg NL, Lennox ES, Dowling RH: Clinical testing of gliadin fractions in coeliac patients. Clin Sci 1984;66:357–364.
Ensari A, Marsh MN, Moriarty KJ, Moore CM, Fido RJ, Tatham AS: Studies in vivo of ω-gliadins in gluten sensitivity (coeliac sprue disease). Clin Sci 1998;95:419–424.
Folk JE, Cole PW: Transglutaminase: Mechanistic features of the active site as determined by kinetic and inhibitor studies. Biochim Biophys Acta 1966;122:244–264.
Folk JE, Chung SI: Transglutaminases. Meth Enzymol 1985;113:358–375.
Ichinose A, Bottenus RE, Davie EW: Structure of transglutaminases. J Biol Chem 1990;265:13411–13414.
Gaudry CA, Verderio E, Aeschlimann D, Cox A, Smith C, Griffin M: Cell surface localization of tissue transglutaminase is dependent on a fibronectin-binding site in its N-terminal β-sandwich domain. J Biol Chem 1999;274:30707–30714.
LeMosy EK, Erickson HP, Beyer WF, Radek JT, Jeong JM, Murthy SNP, Lorand L: Visualization of purified fibronectin-transglutaminase complexes. J Biol Chem 1992;267:7880–7885.
Barsigian C, Stern AM, Martinez J: Tissue (type II) transglutaminase covalently incorporates itself, fibrinogen, or fibronectin into high molecular weight complexes on the extracellular surface of isolated hepatocytes. J Biol Chem 1991;266:22501–22509.
Bowness JM, Folk JE, Timpl R: Identification of a substrate site for liver transglutaminase on the aminopropeptide of type III collagen. J Biol Chem 1987;262:1022–1024.
Kleman JP, Aeschlimann D, Paulsson M, van der Rest M: Transglutaminase-catalyzes cross-linking of fibrils of collagen V/XI in A204 rhabdomyosarcoma cells. Biochemistry 1995;34:13768–13775.
Aeschlimann D, Paulsson M: Cross-linking of laminin-nidogen complexes by tissue transglutaminase. J Biol Chem 1991;266:15308–15317.
Bowness JM, Tarr AH, Wong T: Increased transglutaminase activity during skin wound healing in rats. Biochim Biophys Acta 1988;967:234–240.
Haroon ZA, Hettasch JM, Lai TS, Dewhirst MW, Greenberg CS: Tissue transglutaminase is expressed, active, and directly involved in rat dermal wound healing and angiogenesis. FASEB J 1999;13:1787–1795.
Nunes I, Gleizes PE, Metz CN, Rifkin DB: Latent transforming growth factor-β binding protein domains involved in activation and transglutaminase-dependent cross-linking of latent transforming growth factor-β. J Cell Biol 1997;136:1151–1163.
Kojima S, Nara K, Rifkin DB: Requirement for transglutaminase in the activation of latent transforming growth factor-β in bovine endothelial cells. J Cell Biol 1993;121:439–448.
Halttunen T, Marttinen A, Rantala I, Kainulainen H, Mäki M: Fibroblasts and transforming growth factor β induce organization and differentiation of T84 human epithelial cells. Gastroenterology 1996;111:1252–1262.
Piacentini M, Colizzi V: Tissue transglutaminase: Apoptosis versus autoimmunity. Immunol Today 1999;3:130–134.
Nakaoka H, Perez DM, Baek KJ, Das T, Husain A, Misono K, Im MJ, Graham RM: Gh: A GTP-binding protein with transglutaminase activity and receptor signaling function. Science 1994;264:1593–1596.
Szabolcs M, Sipka S, Csorba S: In vitro cross-linking of gluten into high molecular weight polymers with transglutaminase. Acta Paediatr Hung 1987;28:215–227.
Vartdal F, Johansen BH, Friede T, Thorpe CJ, Stevanovic S, Eriksen JE, Sletten K, Thorsby E, Rammensee HG, Sollid LM: The peptide binding motif of the disease associated HLA-DQ (α1*0501, β1*0201) molecule. Eur J Immunol 1996;26:2764–2772.
Van der Wal Y, Kooy YMC, Drijfhout JW, Amons R, Koning F: Peptide binding characteristics of the coeliac disease-associated DQ(α1*0501, β1*0201) molecule. Immunogenetics 1996;44:246–253.
Godkin A, Friede T, Davenport M, Stevanovic S, Willis A, Jewell D, Hill A, Rammensee HG: Use of eluted peptide sequence data to identify the binding characteristics of peptides to the insulin-dependent diabetes susceptibility allele HLA-DQ8 (DQ 3.2). Int Immunol 1997;9:905–911.
Evans DF, Pye G, Bramley R, Clark AG, Dyson TJ, Hardcastle JD: Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 1988;29:1035–1041.
Fleckenstein B, Molberg Ø, Qiao SW, Schmid DG, Von der Mülbe F, Elgstoen K, Jung G, Sollid LM: Gliadin T cell epitope selection by tissue transglutaminase in celiac disease. J Biol Chem 2002;277:34109–34116.
Arentz-Hansen H, Körner R, Molberg Ø, Quarsten H, Vader W, Kooy YMC, Lundin KEA, Koning F, Roepstorff P, Sollid LM, McAdam SN: The intestinal T cell response to α-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med 2000;191:603–612.
Anderson RP, Degano P, Godkin AJ, Jewell DP, Hill AVS: In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope. Nature Med 2000;6:337–342.
Arentz-Hansen H, McAdam SN, Molberg Ø, Fleckenstein B, Lundin KEA, Jorgensen TJD, Jung G, Roepstorff P, Sollid LM: Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues. Gastroenterology 2002;123:803–809.
Molberg Ø, McAdam SN, Koerner R, Quarsten H, Kristiansen C, Madsen L, Fugger L, Scott H, Norén O, Roepstorff P, Lundin KEA, Sjöström H, Sollid LM: Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med 1998;4:713–717.
Van de Wal Y, Kooy Y, van Veelen P, Pena S, Mearin L, Papadopoulos G, Koning F: Selective deamidation by tissue transglutaminase strongly enhances gliading-specific T cell reactivity. J Immunol 1998;161:1585–1588.
Vader W, Kooy Y, Van Veelen P, De Ru A, Harris D, Benckhuijsen W, Pena S, Mearin L, Drijfhout JW, Koning F: The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides. Gastroenterology 2002;122:1729–1737.
Martucci S, Corazza GR: Spreading and focusing of gluten epitopes in celiac disease. Gastroenterology 2002;122:2072–2075.
Piper JL, Gray GM, Khosla CH: High selectivity of human tissue transglutaminase for immunoactive gliadin peptides: Implications for celiac sprue. Biochemistry 2002;41:386–393.
Shan L, Molberg Ø, Parrot I, Hausch F, Filiz F, Gray GM, Sollid LM, Khosla C: Structural basis for gluten intolerance in celiac sprue. Science 2002;297:2275–2279.
Vader WL, de Ru A, van der Wal Y, Kooy YMC, Benckhuijsen W, Mearin ML, Drijfhout JW, van Veelen P, Koning F: Specificity of tissue transglutaminase explains cereal toxicity in celiac disease. J Exp Med 2002;195:643–649.
Lundin KE, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O, Thorsby E, Sollid LM: Gliadin-specific, HLA-DQ (alpha 1*0501, beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med 1993;178:187–196.
Maiuri L, Picarelli A, Boirivant M, Coletta S, Mazzilli MC, De Vincenzi M, Londei M, Auricchio S: Definition of the initial immunologic modifications upon in vitro gliadin challenge in the small intestine of celiac patients. Gastroenterology 1996;110:1368–1378.
Halstensen TS, Brandtzaeg P: Activated T lymphocytes in the celiac lesion: Non-proliferative activation (CD25) of CD4+ alpha/beta cells in the lamina propria but proliferation (Ki-67) of alpha/beta and gamma/delta cells in the epithelium. Eur J Immunol 1993;23:505–510.
Nilsen EM, Lundin KE, Krajci P, Scott H, Sollid LM, Brandtzaeg P: Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferon gamma. Gut 1995;37:766–776.
Nilsen EM, Jahnsen FL, Lundin KE, Johansen FE, Fausa O, Sollid LM, Jahnsen J, Scott H, Brandtzaeg P: Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology 1998;115:551–563.
Przemioslo RT, Lundin KE, Sollid LM, Nelufer J, Ciclitira PJ: Histological changes in small bowel mucosa induced by gliadin sensitive T lymphocytes can be blocked by anti-interferon gamma antibody. Gut 1995;36:874–879.
Kontakou M, Przemioslo RT, Sturgess RP, Limb GA, Ellis HJ, Day P, Ciclitira PJ: Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge. Gut 1995;37:52–57.
Westerholm-Ormio M, Garioch J, Ketola I, Savilahti E: Inflammatory cytokines in small intestinal mucosa of patients with potential coeliac disease. Clin Exp Immunol 2002;128:94–101.
Forsberg G, Hernell O, Melgar S, Israelsson A, Hammarstrom S, Hammarstrom ML: Paradoxical coexpression of proinflammatory and down-regulatory cytokines in intestinal T cells in childhood celiac disease. Gastroenterology 2002;123:667–678.
Cammarota G, Cuoco L, Cianci R, Pandolfi F, Gasbarrini G: Onset of coeliac disease during treatment with interferon for chronic hepatitis C. Lancet 2000;356:1494–1495.
Monteleone G, Pender SL, Alstead E, Hauer AC, Lionetti P, McKenzie C, MacDonald TT: Role of interferon alpha in promoting T helper cell type 1 responses in the small intestine in coeliac disease. Gut 2001;48:425–429.
Monteleone G, Pender SL, Wathen NC, MacDonald TT: Interferon-alpha drives T cell-mediated immunopathology in the intestine. Eur J Immunol 2001;31:2247–2255.
Salvati VM, MacDonald TT, Bajaj-Elliott M, Borrelli M, Staiano A, Auricchio S, Troncone R, Monteleone G: Interleukin 18 and associated markers of T helper cell type 1 activity in coeliac disease. Gut 2002;50:186–190.
Salvati VM, Bajaj-Elliott M, Poulsom R, Mazzarella G, Lundin KE, Nilsen EM, Troncone R, MacDonald TT: Keratinocyte growth factor and coeliac disease. Gut 2001;49:176–181.
Bajaj-Elliott M, Poulsom R, Pender SL, Wathen NC, MacDonald TT: Interactions between stromal cell-derived keratinocyte growth factor and epithelial transforming growth factor in immune-mediated crypt cell hyperplasia. J Clin Invest 1998;102:1473–1480.
Waldmann TA: The IL-2/IL-15 receptor systems: Targets for immunotherapy (review). J Clin Immunol 2002;22:51–56.
Maiuri L, Ciacci C, Auricchio S, Brown V, Quaratino S, Londei M: Interleukin-15 mediates epithelial changes in celiac disease. Gastroenterology 2000;119:996–1006.
Maiuri L, Ciacci C, Ricciardelli I, Vacca L, Raia V, Auricchio S, Picard J, Osman M, Quaratino S, Londei M: Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 2003;362:30–37.
Schuppan D, Esslinger B, Dieterich W: Innate immunity and coeliac disease. Lancet 2003;362:3–4.
Pender SLF, Tickle SP, Docherty AJP, Howie D, Wathen NC, MacDonal TT: A major role for matrix metalloproteinases in T cell injury in the gut. J Immunol 1997;158:1582–1590.
Daum S, Bauer U, Foss HD, Schuppan D, Stein H, Riecken EO, Ullrich R: Increased expression of mRNA from matrix metalloproteinases-1 and -3 and tissue inhibitor of metalloproteinases-1 in intestinal biopsy specimens from patients with coeliac disease. Gut 1999;44:17–25.
Hansson T, Ulfgren AK, Lindroos E, Dannaeus A, Dahlbom I, Klareskog L: Transforming growth factor-β (TGF-β) and tissue transglutaminase expression in the small intestine in children with coeliac disease. Scand J Immunol 2002;56:530–537.
Brusco G, Muzi P, Ciccocioppo R, Biagi F, Cifone MG, Corazza GR: Transglutaminase and coeliac disease: Endomysial reactivity and small bowel expression. Clin Exp Immunol 1999;118:371–375.
Hausch F, Halttunen T, Mäki M, Khosla C: Design, synthesis and evaluation of gluten peptide analogs as selective inhibitors of human tissue transglutaminase. Chem Biol 2003;10:225–231.
Sollid LM, Molberg O, McAdam S, Lundin KEA: Autoantibodies in coeliac disese: tissue transglutaminase – guilt by association? Gut 1997;41:851–852.
Picarelli A, Maiuri L, Frate A, Greco M, Auricchio S, Londei M: Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease. Lancet 1996;348:1065–1067.
Halttunen T, Mäki M: Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation. Gastroenterology 1999;116:566–572.
Seissler J, Wohlrab U, Wuensche C, Scherbaum WA, Boehm BO: Autoantibodies from patients with coeliac disease recognize distinct functional domains of the autoantigen tissue transglutaminase. Clin Exp Immunol 2001;125:216–221.
Keaveny AP, Offner GD, Bootle E, Nunes DP: No significant difference in antigenicity or tissue transglutaminase substrate specificity of Irish and US wheat gliadins. Dig Dis Sci 2000;45:755–762.
Esposito C, Paparo F, Caputo I, Rossi M, Maglio M, Sblattero D, Not T, Porta R, Auricchio S, Marzari R, Troncone R: Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutaminase activity both in vitro and in situ. Gut 2002;51:177–181.
Biagi F, Ellis HJ, Parnell NDJ, Shidrawi RG, Thomas PD, O’Reilly N, Corazza GR, Ciclitira PJ: A non-toxic analogue of a coeliac-activating gliadin peptide: A basis for immunomodulation? Aliment Pharmacol Ther 1999;13:945–950.
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