Skip to main content
SpringerLink
Log in

Gut Mucosal Immunity to Tissue Transglutaminase in Untreated Celiac Disease and Other Gastrointestinal Disorders

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Tissue transglutaminase antibodies have not previously been measured in gut secretions. IgA anti-tissue transglutaminase and anti-endomysium antibodies were measured in paired serum and whole gut lavage fluid samples from patients with untreated celiac disease (N = 36), other gastrointestinal diseases (N = 235), and healthy volunteers (N = 13). HLA DQ2 typing was performed in the celiac patients. Whole gut lavage IgA anti-tissue transglutaminase antibody concentrations were raised in 83% of celiac patients, 4% of disease controls, and 8% of volunteers, and the antibody concentrations were significantly higher in celiac patients than in controls (P < 0.0001). Whole gut lavage IgA anti-endomysium antibodies were positive in 67% of celiac patients, but in none of the controls. Whole gut lavage, but not serum, IgA anti-tissue transglutaminase antibody concentrations were significantly higher in DQ2 positive than negative celiac patients. In conclusion, whole gut lavage IgA anti-tissue transglutaminase antibody concentrations are higher in untreated celiac disease than in other gastrointestinal diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D.: Identification of tissue transglutaminase as the autoantigen of coeliac disease. Nat Med 3(7):797–801, 1997

    Google Scholar 

  2. Sulkanen S, Halttunen T, Laurila K, Kolho K, Korponay-Szabo IL, Sarnesto A, Savilahti E, Collin P, Maki M: Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 115(6):1322–1328, 1998

    Google Scholar 

  3. Dieterich W, Laag E, Schopper H, Volta U, Ferguson A, Gillett H, Riecken EO, Schuppan D: Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 115(6):1317–1321, 1998

    Google Scholar 

  4. Lock RJ, Pitcher MCL, Unsworth DJ: IgA tissue transglutaminase as a diagnostic marker of gluten sensitive enteropathy. J Clin Pathol 52:274–277, 1999

    Google Scholar 

  5. Troncone R, Maurano F, Rossi M, Micillo M, Greco L, Auricchio S, Salerno G, Salvatore F, Sacchetti L: IgA antibodies to tissue transglutaminase: An effective diagnostic test for celiac disease. J Pediatr 134:166–171, 1999

    Google Scholar 

  6. Biagi F, Ellis HJ, Yiannakou JY, Brusco G, Swift GL, Smith PM, Corazza GR, Ciclitira PJ: Tissue transglutaminase antibodies in celiac disease. Am J Gastroenterol 94(8):2187–2192, 1999

    Google Scholar 

  7. Folk JE: Structure and catalytic properties of hepatic transglutaminase. Ann NY Acad Sci 202:59–76, 1972

    Google Scholar 

  8. Upchurch HF, Conway E, Patterson MK Jr., Birckbichler PJ, Maxwell MD: Cellular transglutaminase has affinity for extracellular matrix. In Vitro Cell Dev Biol 23(11):795–799, 1987

    Google Scholar 

  9. Patel EK, Bruce SE, Bjarnason I, Peters TJ: Rat gastrointestinal transglutaminase: Demonstration of enzyme activity and cell and tissue distributions. Cell Biochem Funct 3:199–203, 1985

    Google Scholar 

  10. Bruce SE, Bjarnason I, Peters TJ: Human jejunal transglutaminase: Demonstration of activity, enzyme kinetics and substrate specificity with special relation to gliadin and coeliac disease. Clin Sci 68:573–579, 1985

    Google Scholar 

  11. Molberg O, Mcadam SN, Korner R, Quarsten H, Kristiansen C, Madsen L, Fugger L, Scott H, Noren O, Roepstorff P, Lundin KEA, Sjostrom H, et al: Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gutderived T cells in celiac disease. Nat Med 4(6):713–717, 1998

    Google Scholar 

  12. Lundin KEA, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O, Thorsby E, Sollid LM: Gliadin-specific, HLADQ( a1*0501, b1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med 178:187–196, 1993

    Google Scholar 

  13. Molberg O, Kett K, Scott H, Thorsby E, Sollid LM, Lundin KEA: Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls. Scand J Immunol 46:103–108, 1997

    Google Scholar 

  14. Sollid LM, Molberg O, McAdam S, Lundin KEA: Autoantibodies in coeliac disease: Tissue transglutaminase–guilt by association? Gut 41:851–852, 1997

    Google Scholar 

  15. O'Mahony S, Arranz E, Barton JR, Ferguson A: Dissociation between systemic and mucosal humoral immune responses in coeliac disease. Gut 32(1):29–35, 1991

    Google Scholar 

  16. Challacombe SJ. Assessing mucosal humoral immunity. Clin Exp Immunol 100:181–182, 1995

    Google Scholar 

  17. O'Mahony S, Barton JR, Crighton S, Ferguson A: Appraisal of gut lavage in the study of intestinal humoral immunity. Gut 31:1341–1344, 1990

    Google Scholar 

  18. Choudari CP, O'Mahony S, Brydon G, Mwantembe O, Ferguson A: Gut lavage fluid protein concentrations: Objective measures of disease activity in inflammatory bowel disease. Gastroenterology 104(4):1064–1071, 1993

    Google Scholar 

  19. Brydon WG, Choudari CP, Ferguson A: Relative specificity for active inflammatory bowel disease of plasma-derived proteins in gut lavage fluid. Eur J Gastroenterol Hepatol 5:269–273, 1993

    Google Scholar 

  20. Gaspari MM, Brennan PT, Solomon SM, Elson CO: A method of obtaining, processing, and analyzing human intestinal secretions for antibody content. J Immunol Methods 110:85–91, 1988

    Google Scholar 

  21. Brown WR, Newcomb RW, Ishizaka K: Proteolytic degradation of exocrine and serum immunoglobulins. J Clin Invest 49:1374–1380, 1970

    Google Scholar 

  22. Jones RG, Payne RB: Data for diagnosis and monitoring. In Clinical Investigation and Statistics in Laboratory Medicine. RG Jones, RB Payne, (eds). London, ACB Venture, 1997, pp. 66–123

    Google Scholar 

  23. Bell JL, Todd JA, McDevitt HO: The molecular basis of HLA-disease association. Adv Hum Genet 18:1–41, 1989

    Google Scholar 

  24. Larhammar D, Hyldig-Nielsen JJ, Servenius B: Exon-intron organization and complete nucleotide sequence of a human major histocompatibility antigen DC beta gene. Proc Natl Acad Sci USA 95:78–82, 1983

    Google Scholar 

  25. Kelly CP, Feighery C, Gallagher RB, Gibney MJ, Weir DG: Mucosal and systemic IgA anti-gliadin antibody in celiac disease. Contrasting patterns of response in serum, saliva, and intestinal secretions. Dig Dis Sci 36(6):743–751, 1991

    Google Scholar 

  26. Engstrom PE, Sundin U, Lavo B, Norhagen G, Hallgren R, Smith CIE: Class and subclass-associated specificity differences of anti-gliadin antibodies from mucosa and serum. Immunology 77:604–608, 1992

    Google Scholar 

  27. Lancaster-Smith M, Kumar P, Marks R, Clark ML, Dawson AM: Jejunal mucosal immunoglobulin-containing cells and jejunal fluid immunoglobulins in adult coeliac disease and dermatitis herpetiformis. Gut 15:371–376, 1974

    Google Scholar 

  28. Volta U, Molinaro N, Fratangelo D, Bianchi FB: IgA subclass antibodies to gliadin in serum and intestinal juice of patients with coeliac disease. Clin Exp Immunol 80:192–195, 1990

    Google Scholar 

  29. Mwantembe O: The immunological effects of elemental diets in inflammatory bowel disease. Edinburgh, University of Edinburgh, 1992, 179 pp

    Google Scholar 

  30. Colombel JF, Mascart-Lemone F, Nemeth J, Vaerman JP, Dive C, Rambaud JC: Jejunal immunoglobulin and antigliadin antibody secretion in adult coeliac disease. Gut 31:1345–1349, 1990

    Google Scholar 

  31. Crabbe PA, Carbonara AO, Heremans JF: The normal human intestinal mucosa as a major source of plasma cells containing gamma-A-immunoglobulin. Lab Invest 14(3):235–248, 1965

    Google Scholar 

  32. Rosekrans PCM, Meijer CJLM, Van Der Wal AM, Cornelisse CJ, Lindeman J: Immunoglobulin containing cells in inflammatory bowel disease of the colon: A morphometric and immunohistochemical study. Gut 21:941–947, 1980

    Google Scholar 

  33. Ferguson A, Humphreys K, Croft N. Technical reports: Results of immunological tests on faecal extracts are likely to be extremely misleading. Clin Exp Immunol 99:70–75, 1995

    Google Scholar 

  34. Collin P, Maki M, Keyrilainen O, Hallstrom O, Reunala T, Pasternack A: Selective IgA deficiency and coeliac disease. Scand J Gastroenterol 27:367–371, 1992

    Google Scholar 

  35. Webster ADB, Slavin G, Shiner M, Platts-Mills TAE, Asherson GL: Coeliac disease with severe hypogammaglobulinaemia. Gut 22:153–157, 1981

    Google Scholar 

  36. Halttunen T, Maki M: Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation. Gastroenterology 116:566–572, 1999

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastrointestinal Unit, Department of Medical Sciences, University of Edinburgh, Edinburgh, Scotland

    Anna Dahele, Marian C. Aldhous, Kathleen Kingstone, Kennneth Humphreys, John Bode & Subrata Ghosh

  2. Department of Pathology, Western General Hospital, Edinburgh, Scotland

    Margaret McIntyre

Authors
  1. Anna Dahele
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marian C. Aldhous
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kathleen Kingstone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kennneth Humphreys
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John Bode
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Margaret McIntyre
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Subrata Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dahele, A., Aldhous, M.C., Kingstone, K. et al. Gut Mucosal Immunity to Tissue Transglutaminase in Untreated Celiac Disease and Other Gastrointestinal Disorders. Dig Dis Sci 47, 2325–2335 (2002). https://doi.org/10.1023/A:1020155831849

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020155831849

Search

Navigation