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Mortality Excess in Individuals with Elevated IgA Anti-Transglutaminase Antibodies: The KORA/MONICA Augsburg Cohort Study 1989–1998

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Abstract

Objectives

: Immunoglobulin A (IgA) autoantibodies to tissue transglutaminase (tTG) are commonly used for screening and diagnosing of celiac disease. We examined the hypothesis that elevated IgA anti-tTG antibodies were associated with higher all-cause mortality risk.

Methods

The cohort, 2333 men and 2300 women, was based on the follow-up of participants of a representative population-based survey in Southern Germany (KORA/MONICA Augsburg project) conducted in 1989–1990. The endpoint for the vital status with cause of death was the year 1998. The sera drawn at baseline and stored at −80 °C, were recently screened with an IgA enzyme-linked immunosorbent assay (ELISA) using human recombinant tTG. Age-standardized mortality rates and age-adjusted hazard ratios were calculated.

Results

From the 4633 sera analyzed, 63 had an IgA anti-tTG concentration ≥7 AU/ml. Of these 63 individuals, 15 died between 1989 and 1998. The age-adjusted hazard ratio (HRa) of all-cause mortality was 1.86 (95% CI: 1.01–3.41) and 3.92 (95% CI: 1.44–10.71) for men and women, respectively. The excess of cancer mortality was even higher with an HRa of 2.47 (95% CI: 0.89–6.83) in men and of 6.65 (95% CI: 2.04–21.63) in women.

Conclusions:

Individuals with elevated IgA anti-tTG antibodies had a highly increased mortality risk, particularly due to cancer. New studies are necessary to clarify if this increased risk is due to undiagnosed celiac disease or/and if this elevated IgA anti-tTG antibodies level is a marker of serious diseases like cancer, chronic liver disease or end-stage heart failure.

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Reference

  1. Schuppan D. 2000 Current concepts of celiac disease pathogenesis. Gastroenterology 119:234–242

    Article  PubMed  CAS  Google Scholar 

  2. Korponay-Szabo IR, Sulkanen S, Halttunen T, Maurano F, Rossi M, Mazzarella G, Laurila K, Troncone R, Maki M. 2000 Tissue transglutaminase is the target in both rodent and primate tissues for celiac disease-specific autoantibodies. J Pediatr Gastroenterol Nutr 31:520–527

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Blackwell PJ, Hill PG, Holmes GK. 2002 Autoantibodies to human tissue transglutaminase: Superior predictors of coeliac disease. Scand J Gastroenterol 37:1282–1285

    Article  PubMed  CAS  Google Scholar 

  6. Sblattero D, Berti I, Trevisiol C, Marzari R, Tommasini A, Bradbury A, Fasano A, Ventura A, Not T. 2000 Human recombinant tissue transglutaminase ELISA: An innovative diagnostic assay for celiac disease. Am J Gastroenterol 95:1253–1257

    Article  PubMed  CAS  Google Scholar 

  7. Peracchi M, Trovato C, Longhi M, Gasparin M, Conte D, Tarantino C, Prati D, Bardella MT. 2002 Tissue transglutaminase antibodies in patients with end-stage heart failure. Am J Gastroenterol 97:2850–2854

    Article  PubMed  CAS  Google Scholar 

  8. Vecchi M, Folli C, Donato MF, Formenti S, Arosio E, de Franchis R. 2003 High rate of positive anti-tissue transglutaminase antibodies in chronic liver disease. Role of liver decompensation and of the antigen source. Scand J Gastroenterol 38:50–54

    Article  PubMed  CAS  Google Scholar 

  9. Reeves GE, Burns C, Hall ST, Gleeson M, Lemmert K, Clancy RL. 2000 The measurement of IgA and IgG transglutaminase antibodies in celiac disease: A comparison with current diagnostic methods. Pathology 32:181–185

    Article  PubMed  CAS  Google Scholar 

  10. Sardy M, Odenthal U, Karpati S, Paulsson M, Smyth N. 1999 Recombinant human tissue transglutaminase ELISA for the diagnosis of gluten-sensitive enteropathy. Clin Chem 45:2142–2149

    PubMed  CAS  Google Scholar 

  11. Farrell RJ, Kelly CP. 2002 Celiac sprue. N Engl J Med 346:180–188

    Article  PubMed  CAS  Google Scholar 

  12. WHO MONICA Project Principal Investigators 1988 The World Health Organization MONICA Project (Monitoring trends and determinants in cardiovascular disease): a major international collaboration. J.Clin Epidemiol 41:105–114

    Article  Google Scholar 

  13. Hense H-W, Filipiak B, Doering A, Stieber J, Liese A, Keil U. 1998 Ten-Year trends of Cardiovascular Risk Factors in the MONICA Augsburg Region in Southern Germany Results from the 1984/1985, 1989/1990, and 1994/1995 Surveys. CVD Prev 1:318–327

    Google Scholar 

  14. Parnell ND, Ciclitira PJ. 1999 Review article: Coeliac disease and its management. Aliment Pharmacol Ther 13:1–13

    Article  PubMed  CAS  Google Scholar 

  15. Holmes GK, Prior P, Lane MR, Pope D, Allan RN. 1989 Malignancy in coeliac disease–effect of a gluten free diet. Gut 30:333–338

    Article  PubMed  CAS  Google Scholar 

  16. Loftus CG, Loftus EV Jr. 2002 Cancer risk in celiac disease. Gastroenterology 123:1726–1729

    Article  PubMed  Google Scholar 

  17. Logan RF, Rifkind EA, Turner ID, Ferguson A. 1989 Mortality in celiac disease. Gastroenterology 97:265–271

    PubMed  CAS  Google Scholar 

  18. Peters U, Askling J, Gridley G, Ekbom A, Linet M. 2003 Causes of death in patients with celiac disease in a population-based Swedish cohort. Arch Intern Med 163:1566–1572

    Article  PubMed  Google Scholar 

  19. Corrao G, Corazza GR, Bagnardi V, Brusco G, Ciacci C, Cottone M, Sategna GC, Usai P, Cesari P, Pelli MA, Loperfido S, Volta U, Calabro A, Certo M. 2001 Mortality in patients with coeliac disease and their relatives: A cohort study. Lancet 358:356–361

    Article  PubMed  CAS  Google Scholar 

  20. Catassi C, Fabiani E, Corrao G, Barbato M, De Renzo A, Carella AM, Gabrielli A, Leoni P, Carroccio A, Baldassarre M, Bertolani P, Caramaschi P, Sozzi M, Guariso G, Volta U, Corazza GR. 2002 Risk of non-Hodgkin lymphoma in celiac disease. JAMA 287:1413–1419

    Article  PubMed  Google Scholar 

  21. Nielsen OH, Jacobsen O, Pedersen ER, Rasmussen SN, Petri M, Laulund S, Jarnum S. 1985 Non-tropical sprue. Malignant diseases and mortality rate. Scand J Gastroenterol 20:13–18

    Article  PubMed  CAS  Google Scholar 

  22. Holmes GK. 1997 Celiac disease and malignancy. J Pediatr Gastroenterol Nutr 24:S20–S23

    Article  PubMed  CAS  Google Scholar 

  23. Marsh MN. 1997 Is celiac disease (gluten sensitivity) a premalignant disorder? J Pediatr Gastroenterol Nutr 24:S25–S27

    PubMed  CAS  Google Scholar 

  24. Csizmadia CG, Mearin ML, von Blomberg BM, Brand R, Verloove-Vanhorick SP. 1999 An iceberg of childhood coeliac disease in the Netherlands. Lancet 353:813–814

    Article  PubMed  CAS  Google Scholar 

  25. Maki M, Mustalahti K, Kokkonen J, Kulmala P, Haapalahti M, Karttunen T, Ilonen J, Laurila K, Dahlbom I, Hansson T, Hopfl P, Knip M. 2003 Prevalence of coeliac disease among children in Finland. N Engl J Med 348:2517–2524

    Article  PubMed  Google Scholar 

  26. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PHR, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K. 2003 Prevalence of celiac disease in at-risk and not-at-risk groups in the United States – A large multicenter study. Arch Intern Med 163:286–292

    Article  PubMed  Google Scholar 

  27. Leffler D, Saha S, Farrell RJ. 2003 Celiac disease. Am J Manag Care 9:825–831

    PubMed  Google Scholar 

  28. Collin P, Reunala T, Pukkala E, Laippala P, Keyrilainen O, Pasternack A. 1994 Coeliac disease-associated disorders and survival. Gut 35:1215–1218

    Article  PubMed  CAS  Google Scholar 

  29. Lowel H, Meisinger C, Heier M, Hormann A, Kuch B, Gostomzyk J, Koenig W. 2002 Sex specific trends of sudden cardiac death and acute myocardial infarction: Results of the population-based KORA/MONICA-Augsburg Register 1985–1998. Deutsche Medizinische Wochenschrift 127:2311–2316

    Article  PubMed  Google Scholar 

  30. Doring A, Filipiak B, Stieber J, Keil U. 1993 Trends in alcohol intake in a southern German population from 1984–1985 to 1989–1990: Results of the MONICA Project Augsburg. J Stud Alcohol 54:745–749

    PubMed  Google Scholar 

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Acknowledgements

This study has been carried out with financial support from the Commission of the European Communities, specific RTD programme “Quality of Life and Management of Living Resources” QLK1-CT-1999-00037, “Evaluation of the prevalence of the celiac disease and its genetic components in the European population”. It does not necessarily reflect its views and in no way anticipates the Commission’s future policy in this area.

We are grateful to Angela Döring, Mathematician and Medical Doctor, (GSF-National Research Center for Environment and Health) for statistical advice.

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Correspondence to Margit Heier.

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Metzger, MH., Heier, M., Mäki, M. et al. Mortality Excess in Individuals with Elevated IgA Anti-Transglutaminase Antibodies: The KORA/MONICA Augsburg Cohort Study 1989–1998. Eur J Epidemiol 21, 359–365 (2006). https://doi.org/10.1007/s10654-006-9002-4

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  • DOI: https://doi.org/10.1007/s10654-006-9002-4

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