Abstract
Background The significance of the presence of anti-gliadin antibodies in patients affected by celiac disease is still unclear. It is hypothesized that gliadin deamidation, catalysed by transglutaminase, plays a role in favoring the antigen presentation. Aim To determine the immunoreactivity of anti-gliadin antibodies from untreated celiac patients to transglutaminase deamidated gliadins. Materials and methods Gliadins from wheat flour underwent enzymatic digestion and were deamidated or cysteamine-transamidated by transglutaminase. Immunoreactivity of anti-gliadin antibodies from untreated adult celiac patients sera was evaluated by means of a competitive enzyme-linked immunosorbent assay (ELISA) method. Results Gliadin deamidation increased antibodies immunoreactivity from 25% to 50% while cysteamine incorporation into the gliadin peptides resulted in an immunoreactivity decrease. Conclusions Increased immunoreactivity of transglutaminase deamidated gliadins tested with anti-gliadin antibodies from untreated adult celiac patients supports the hypothesis of a pivotal role of gliadin deamidation in the pathomechanism of celiac disease.
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References
Schuppan D (2000) Current concepts of celiac disease pathogenesis. Gastroenterology 119:234–242
Howdle PD (2006) Gliadin, glutenin or both? The search for the Holy Grail in coeliac disease. Eur J Gastroenterol Hepatol 18:703–706
van Heel DA, West J (2006) Recent advances in coeliac disease. Gut 55:1037–1046
Griffin M, Casadio R, Bergamini CM (2002) Transglutaminases: nature’s biological glues. Biochem J 368:377–396
Shan L, Molberg O, Parrot I, Hausch F, Filiz F, Gray GM, Sollid LM, Khosla C (2002) Structural basis for gluten intolerance in celiac sprue. Science 297:2275–2279
Aleanzi M, Demonte AM, Esper C, Garcilazo S, Waggener M (2001) Celiac disease: antibody recognition against native and selectively deamidated gliadin peptides. Clin Chem 47:2023–2028
Osman AA, Gunnel T, Dietl A, Uhlig HH, Amin M, Fleckenstein B, Richter T, Mothes T (2000) B cell epitopes of gliadin. Clin Exp Immunol 121:248–254
Rostom A, Murray JA, Kagnoff MF (2006) American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology 131:1981–2002
Capelli L, Forlani F, Perini F, Guerrieri N, Cerletti P, Righetti PG (1998) Wheat cultivar discrimination by capillary electrophoresis of gliadins in isoelectric buffers. Electrophoresis 19:311–318
Dolfini E, Elli L, Dasdia T, Bufardeci B, Colleoni MP, Costa B, Floriani I, Falini ML, Guerrieri N, Forlani F, Bardella MT (2002) In vitro cytotoxic effect of bread wheat gliadin on the LoVo human adenocarcinoma cell line. Toxicol In Vitro 16:331–337
Mamone G, Ferranti P, Melck D, Tafuro F, Longobardo L, Chianese L, Addeo F (2004) Susceptibility to transglutaminase of gliadin peptides predicted by a mass spectrometry-based assay. FEBS Lett 562:177–182
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77
Berti C, Roncoroni L, Falini ML, Caramanico R, Dolfini E, Bardella MT, Elli L, Terrani C, Forlani F (2007) Celiac-related properties of chemically and enzymatically modified gluten proteins. J Agric Food Chem 55:2482–2488
Wieser H (1996) Relation between gliadin structure and coeliac toxicity. Acta Paediatr 412(Suppl):3–9
Stepniak D, Koning F (2006) Celiac disease–sandwiched between innate and adaptive immunity. Hum Immunol 67:460–468
Spaenij-Dekking L, Kooy-Winkelaar Y, van Veelen P, Drijfhout JW, H Jonker van Soest L, Smulders MJ, Bosch D, Gilissen LJ, Koning F (2005) Natural variation in toxicity of wheat: potential for selection of nontoxic varieties for celiac disease patients. Gastroenterology 129:797–806
Maiuri L, Ciacci C, Ricciardelli I, Vacca L, Raia V, Auricchio S, Picard J, Osman M, Quaratino S, Londei M (2003) Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 362:30–37
Ewe K, Schwartz S, Petersen S, Press AG (1999) Inflammation does not decrease intraluminal pH in chronic inflammatory bowel disease. Dig Dis Sci 44:1434–1439
Malandain H (2005) Transglutaminases: a meeting point for wheat allergy, celiac disease, and food safety. Allerg Immunol (Paris) 37:397–403
Yokoyama K, Nio N, Kikuchi Y (2004) Properties and applications of microbial transglutaminase. Appl Microbiol Biotechnol 64:447–454
Prince HE (2006) Evaluation of the INOVA diagnostics enzyme-linked immunosorbent assay kits for measuring serum immunoglobulin G (IgG) and IgA to deamidated gliadin peptides. Clin Vaccine Immunol 13:150–151
Hill ID (2005) What are the sensitivity and specificity of serologic tests for celiac disease? Do sensitivity and specificity vary in different populations? Gastroenterology 128:S25–S32
Volta U, Granito A, Fiorini E, Parisi C, Piscaglia M, Pappas G, Muratori P, Bianchi FB (2007) Usefulness of antibodies to deamidated gliadin peptides in celiac disease diagnosis and follow-up. Dig Dis Sci. doi: 10.1007/s10620-007-0058-0
Kaukinen K, Collin P, Laurila K, Kaartinen T, Partanen J, Maki M (2007) Resurrection of gliadin antibodies in coeliac disease. Deamidated gliadin peptide antibody test provides additional diagnostic benefit. Scand J Gastroenterol 42:1428–1433
Ankelo M, Kleimola V, Simell S, Simell O, Knip M, Jokisalo E, Tarkia M, Westerlund A, He Q, Viander M, Ilonen J, Hinkkanen AE (2007) Antibody responses to deamidated gliadin peptide show high specificity and parallel antibodies to tissue transglutaminase in developing coeliac disease. Clin Exp Immunol 150:285–293
Niveloni S, Sugai E, Cabanne A, Vazquez H, Argonz J, Smecuol E, Moreno ML, Nachman F, Mazure R, Kogan Z, Gomez JC, Maurino E, Bai JC (2007) Antibodies against synthetic deamidated gliadin peptides as predictors of celiac disease: prospective assessment in an adult population with a high pretest probability of disease. Clin Chem 53:2186–2192
Liu E, Li M, Emery L, Taki I, Barriga K, Tiberti C, Eisenbarth GS, Rewers MJ, Hoffenberg EJ (2007) Natural history of antibodies to deamidated gliadin peptides and transglutaminase in early childhood celiac disease. J Pediatr Gastroenterol Nutr 45:293–300
Agardh D (2007) Antibodies against synthetic deamidated gliadin peptides and tissue transglutaminase for the identification of childhood celiac disease. Clin Gastroenterol Hepatol 5:1276–1281
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The authors particularly thank the Lombardy Section of the Italian Association for Celiac Disease for its support.
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Falini, M.L., Elli, L., Caramanico, R. et al. Immunoreactivity of Antibodies Against Transglutaminase-Deamidated Gliadins in Adult Celiac Disease. Dig Dis Sci 53, 2697–2701 (2008). https://doi.org/10.1007/s10620-007-0191-9
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DOI: https://doi.org/10.1007/s10620-007-0191-9