Mortality Excess in Individuals with Elevated IgA Anti-transglutaminase Antibodies: the KORA/MONICA Augsburg Cohort Study 1989-1998

Overview

Journal Eur J Epidemiol

Specialty Public Health

Date 2006 May 2

PMID 16649072

Citations 35

Authors

Marie-Helene Metzger

Margit Heier

Markku Maki

Enzo Bravi

Andrea Schneider

Hannelore Lowel

Thomas Illig

Detlef Schuppan

Heinz-Erich Wichmann

Affiliations

Soon will be listed here.

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 degrees 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>or=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 HR(a) 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.

Citing Articles

Vulnerability in Children with Celiac Disease: Findings from a Scoping Review.

Macedo L, Catarino M, Festas C, Alves P Children (Basel). 2024; 11(6).

PMID: 38929308 PMC: 11201835. DOI: 10.3390/children11060729.

Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder.

Niemela O, Bloigu A, Bloigu R, Nivukoski U, Kultti J, Pohjasniemi H Int J Mol Sci. 2023; 24(17).

PMID: 37685930 PMC: 10487441. DOI: 10.3390/ijms241713124.

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek M, Thom H, Sheppard A, Keeney E, ODonnell R, Jackson J Health Technol Assess. 2022; 26(44):1-310.

PMID: 36321689 PMC: 9638887. DOI: 10.3310/ZUCE8371.

Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study.

Elli L, Bascunan K, di Lernia L, Bardella M, Doneda L, Soldati L BMC Med. 2020; 18(1):42.

PMID: 32172690 PMC: 7075003. DOI: 10.1186/s12916-020-1511-6.

Preparation and Characterization of Avenin-Enriched Oat Protein by Chill Precipitation for Feeding Trials in Celiac Disease.

Tanner G, Juhasz A, Florides C, Nye-Wood M, Bekes F, Colgrave M Front Nutr. 2019; 6:162.

PMID: 31681788 PMC: 6803533. DOI: 10.3389/fnut.2019.00162.

References

Parnell N, Ciclitira P . Review article: coeliac disease and its management. Aliment Pharmacol Ther. 1999; 13(1):1-13. DOI: 10.1046/j.1365-2036.1999.00448.x. View

Farrell R, Kelly C . Celiac sprue. N Engl J Med. 2002; 346(3):180-8. DOI: 10.1056/NEJMra010852. View

Peters U, Askling J, Gridley G, Ekbom A, Linet M . Causes of death in patients with celiac disease in a population-based Swedish cohort. Arch Intern Med. 2003; 163(13):1566-72. DOI: 10.1001/archinte.163.13.1566. View

Holmes G, Prior P, LANE M, Pope D, Allan R . Malignancy in coeliac disease--effect of a gluten free diet. Gut. 1989; 30(3):333-8. PMC: 1378455. DOI: 10.1136/gut.30.3.333. View

Marsh M . Is celiac disease (gluten sensitivity) a premalignant disorder?. J Pediatr Gastroenterol Nutr. 1997; 24(5):S25-7. DOI: 10.1097/00005176-199700001-00008. View

Vecchi M, Folli C, Donato M, Formenti S, Arosio E, de Franchis R . High Rate of Positive Anti-Tissue Transglutaminase Antibodies in Chronic Liver Disease. Scand J Gastroenterol. 2016; 38(1):50-54. DOI: 10.1080/00365520310000438. View

Leffler D, Saha S, Farrell R . Celiac disease. Am J Manag Care. 2004; 9(12):825-31. View

Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken E . Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med. 1997; 3(7):797-801. DOI: 10.1038/nm0797-797. View

Reeves G, Burns C, Hall S, Gleeson M, Lemmert K, Clancy R . The measurement of IgA and IgG transglutaminase antibodies in celiac disease: a comparison with current diagnostic methods. Pathology. 2000; 32(3):181-5. View

10.

Lowel H, Meisinger C, Heier M, Hormann A, Kuch B, Gostomzyk J . [Sex specific trends of sudden cardiac death and acute myocardial infarction: results of the population-based KORA/MONICA-Augsburg register 1985 to 1998]. Dtsch Med Wochenschr. 2002; 127(44):2311-6. DOI: 10.1055/s-2002-35181. View

11.

Fasano A, Berti I, Gerarduzzi T, Not T, Colletti R, Drago S . 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(3):286-92. DOI: 10.1001/archinte.163.3.286. View

12.

Schuppan D . Current concepts of celiac disease pathogenesis. Gastroenterology. 2000; 119(1):234-42. DOI: 10.1053/gast.2000.8521. View

13.

Korponay-Szabo I, Sulkanen S, Halttunen T, Maurano F, Rossi M, Mazzarella G . Tissue transglutaminase is the target in both rodent and primate tissues for celiac disease-specific autoantibodies. J Pediatr Gastroenterol Nutr. 2001; 31(5):520-7. DOI: 10.1097/00005176-200011000-00013. View

14.

Blackwell P, Hill P, Holmes G . Autoantibodies to human tissue transglutaminase: superior predictors of coeliac disease. Scand J Gastroenterol. 2002; 37(11):1282-5. DOI: 10.1080/003655202761020551. View

15.

Sblattero D, Berti I, Trevisiol C, Marzari R, Tommasini A, Bradbury A . Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for celiac disease. Am J Gastroenterol. 2000; 95(5):1253-7. DOI: 10.1111/j.1572-0241.2000.02018.x. View

16.

Doring A, Filipiak B, Stieber J, Keil U . Trends in alcohol intake in a southern German population from 1984-1985 to 1989-1990: results of the MONICA Project Augsburg. J Stud Alcohol. 1993; 54(6):745-9. DOI: 10.15288/jsa.1993.54.745. View

17.

Sardy M, Odenthal U, Karpati S, Paulsson M, Smyth N . Recombinant human tissue transglutaminase ELISA for the diagnosis of gluten-sensitive enteropathy. Clin Chem. 1999; 45(12):2142-9. View

18.

Holmes G . Celiac disease and malignancy. J Pediatr Gastroenterol Nutr. 1997; 24(5):S20-3; discussion S23-4. DOI: 10.1097/00005176-199700001-00007. View

19.

Collin P, Reunala T, Pukkala E, Laippala P, KEYRILAINEN O, Pasternack A . Coeliac disease--associated disorders and survival. Gut. 1994; 35(9):1215-8. PMC: 1375696. DOI: 10.1136/gut.35.9.1215. View

20.

Peracchi M, Trovato C, Longhi M, Gasparin M, Conte D, Tarantino C . Tissue transglutaminase antibodies in patients with end-stage heart failure. Am J Gastroenterol. 2002; 97(11):2850-4. DOI: 10.1111/j.1572-0241.2002.07033.x. View