Correlation of Serum Tissue Transglutaminase Antibody Levels and Marsh Grading of Duodenal Biopsy in Patients of Celiac Disease
Keywords:
Malabsorption, Celiac disease (CD), duodenal biopsy, modified Marsh grading, serum anti tissue transglutaminase (anti-tTG) test
Abstract
Background: Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated in genetically predisposed individuals by ingestion of wheat gluten and related proteins of barley and rye. It is an under-diagnosed gluten-sensitive enteropathy, usually presenting with atypical/extra-intestinal features. Duodenal biopsy is considered as the gold standard in the diagnosis of CD. Serum anti tissue transglutaminase (anti-tTG) antibodies is auto antibodies directed against tissue transglutaminase (tTG) enzyme. Aims and objective: The aim of the study is to find out the prevalence of CD among clinically suspected cases of malabsorption, to assess the correlation of anti-tTG levels with modified Marsh grading of duodenal biopsy, to find out sensitivity, specificity and predictive values of anti-tTG test and to calculate the cut off values of anti-tTG diagnostic of high grade CD. Methodology: The present study included 118 clinically suspected patients of malabsorption in which both duodenal biopsy and anti-tTG test was done. The mucosal damage graded according to the modified Marsh grading and anti-tTG tests were done in serum using ELISA kit. Results: The prevalence of CD among clinically suspected cases of malabsorption was 12.7%. The incidence was highest in middle aged male patients. The most common clinical symptom was chronic diarrhea and commonest presenting sign was anemia. Anti-tTG levels were found to be proportionately increasing with the severity of CD and showed a positive correlation(r=0.433). Patients with anemia and chronic diarrhea showed statistically significant (p value=0.0242 and 0.0089 respectively) mean anti-tTG levels in Celiac patients in relation to non-Celiac patients. Although the mean levels of anti-tTG was 6.3 times higher than baseline in grade 3 disease, the ROC analysis showed that anti-tTG in isolation had no significance in exactly grading the disease (AUC=0.30). Conclusion: Positive correlation was found between anti-tTG levels and modified Marsh grading. Anti-tTG showed proportionate increase with severity of duodenal damage. Anti-tTG test showed low sensitivity (42.86%) and high specificity (84.34%). Hence it is not a reliable tool in isolation to screen CD but should be used in combination with duodenal biopsy. It can be used to assess the severity of CD and for follow up.References
1. Kumar V, Abbas A, Fausto N, Aster J. Robbins and Cotran pathologic basis of disease. 8th ed. Chapter 17, The gastrointestinal tract; p.793-94.
2. Kang JY, Kang AH, Green A, Gwee KA, Ho KY. Systemat¬ic review: worldwide variation in the frequency of coeliac disease and changes over time. Aliment PharmacolTher2013; 38: 226-45.
3. Briani C, Samaroo D, Alaedini A. Celiac disease: From gluten to autoimmunity. Autoimmun Rev 2008; 7: 644-50.
4. Setty M, Hormaza L, Guandalini S. Celiac disease: Risk assessment, diagnosis, and monitoring. Mol DiagnTher 2008; 12:289-98.
5. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago Set al. Prevalence of Celiac disease in at-risk and not-at-risk groups in the Unites States: a large multicenter study. Arch Intern Med 2003; 163: 286–92.
6. Green PH, Jabri B. Coeliac disease. Lancet 2003; 362: 383–91.
7. Ciclitira PJ, King AL, Fraser JS.AGA technical review on Celiac Sprue. American Gastroenterological Association.Gastroenterology. 2001;120: 1526-40.
8. Rostami K, Kerckhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in untreated Celiac disease: disappointing in clinical practice. Am J Gastroenterol1999; 94: 888–94.
9. Oberhuber G, Granditsch G. The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J GastroenterolHepatol 1999; 11: 1185–94.
10. Heredia PC, Castro PF. Adult Celiac disease. Rev Med Chil2007; 135:1186-94.
11. Lionetti E, Catasssi C. New clues in Celiac disease epidemiology, pathogenesis, clinical manifestations, and treatment.Int Rev Immunol 2011; 30: 219–31.
12. Tommasini A, Not T, Kiren V, Baldas V, Santon D. Mass screening for Celiac disease using antihuman transglutaminase antibody assay. Arch Dis Child 2004; 89:512-5.
13. Rahmati A, Shakeri R, Sohrabi MR, Alipour A, Boghratian AH, Setareh M et al. Correlation of Tissue Transglutaminase Antibody with Duodenal Histologic Marsh Grad¬ing. Middle East J Dig Dis 2014; 6:131-6.
14. Kalhan S, Joseph P, Sharma S, Dubey S, Dudani S, Dixit M. Comparative study of histopathological Marsh grading with clinical and serological parameters in Celiac iceberg of north India. Indian J PatholMicrobiol 2011; 54:279-83.
15. Singh P, Kurray L, Agnihotri A, Das P, Verma AK, Sreenivas V, et al. Titers of Anti-tissue Transglutaminase Antibody Correlate Well With Severity of Villous Abnormalities in Celiac Disease. J ClinGastroenterol 2015; 49:212–217
16. Bhattacharya M, Lomash A , Sakhuja P, Dubey AP, Kapoor S. Clinical and histopathological correlation of duodenal biopsy with IgA anti-tissue transglutaminase titers in children with Celiac disease. Indian J Gastroenterol2014 Jul; 33(4):350-4.
17. Emami MH, Karimi S, Kouhestani S, Hashemi M, Taheri H. Diagnostic accuracy of IgA anti-tissue transglutaminase in patients suspected of having coeliac disease in Iran. J Gastrointestin Liver Dis. 2008 Jun;17(2):141-6.
18. Zanini B, Magni A, Caselani F, Lanzarotto F, Carabellese N, VillanacciV,et al., High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of Celiac disease. Dig Liver Dis 2012; 44: 280-5.
19. Fernández ML, Vivas S, Ruiz de Morales JM, Marugan JM. Usefulness of anti-transglutaminase antibodies in the diagnosis of Celiac disease.GastroenterolHepatol 2005; 28: 437-40.
20. Abrams JA, Brar P, Diamond B, Rotterdam H, Green PH. Utility in clinical practice of immunoglobulin a anti-tissue transglutaminase antibody for the diagnosis of Celiac disease. ClinGastroenterolHepatol 2006; 4: 726-730.
21. Vivas S, Ruiz de Morales JG, Riestra S, Arias L, Fuentes D, Alvarez N, et al. Duodenal biopsy may be avoided when high transglutaminase antibody titers are present.World J Gastroenterol 2009; 15:4775-80.
2. Kang JY, Kang AH, Green A, Gwee KA, Ho KY. Systemat¬ic review: worldwide variation in the frequency of coeliac disease and changes over time. Aliment PharmacolTher2013; 38: 226-45.
3. Briani C, Samaroo D, Alaedini A. Celiac disease: From gluten to autoimmunity. Autoimmun Rev 2008; 7: 644-50.
4. Setty M, Hormaza L, Guandalini S. Celiac disease: Risk assessment, diagnosis, and monitoring. Mol DiagnTher 2008; 12:289-98.
5. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago Set al. Prevalence of Celiac disease in at-risk and not-at-risk groups in the Unites States: a large multicenter study. Arch Intern Med 2003; 163: 286–92.
6. Green PH, Jabri B. Coeliac disease. Lancet 2003; 362: 383–91.
7. Ciclitira PJ, King AL, Fraser JS.AGA technical review on Celiac Sprue. American Gastroenterological Association.Gastroenterology. 2001;120: 1526-40.
8. Rostami K, Kerckhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in untreated Celiac disease: disappointing in clinical practice. Am J Gastroenterol1999; 94: 888–94.
9. Oberhuber G, Granditsch G. The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J GastroenterolHepatol 1999; 11: 1185–94.
10. Heredia PC, Castro PF. Adult Celiac disease. Rev Med Chil2007; 135:1186-94.
11. Lionetti E, Catasssi C. New clues in Celiac disease epidemiology, pathogenesis, clinical manifestations, and treatment.Int Rev Immunol 2011; 30: 219–31.
12. Tommasini A, Not T, Kiren V, Baldas V, Santon D. Mass screening for Celiac disease using antihuman transglutaminase antibody assay. Arch Dis Child 2004; 89:512-5.
13. Rahmati A, Shakeri R, Sohrabi MR, Alipour A, Boghratian AH, Setareh M et al. Correlation of Tissue Transglutaminase Antibody with Duodenal Histologic Marsh Grad¬ing. Middle East J Dig Dis 2014; 6:131-6.
14. Kalhan S, Joseph P, Sharma S, Dubey S, Dudani S, Dixit M. Comparative study of histopathological Marsh grading with clinical and serological parameters in Celiac iceberg of north India. Indian J PatholMicrobiol 2011; 54:279-83.
15. Singh P, Kurray L, Agnihotri A, Das P, Verma AK, Sreenivas V, et al. Titers of Anti-tissue Transglutaminase Antibody Correlate Well With Severity of Villous Abnormalities in Celiac Disease. J ClinGastroenterol 2015; 49:212–217
16. Bhattacharya M, Lomash A , Sakhuja P, Dubey AP, Kapoor S. Clinical and histopathological correlation of duodenal biopsy with IgA anti-tissue transglutaminase titers in children with Celiac disease. Indian J Gastroenterol2014 Jul; 33(4):350-4.
17. Emami MH, Karimi S, Kouhestani S, Hashemi M, Taheri H. Diagnostic accuracy of IgA anti-tissue transglutaminase in patients suspected of having coeliac disease in Iran. J Gastrointestin Liver Dis. 2008 Jun;17(2):141-6.
18. Zanini B, Magni A, Caselani F, Lanzarotto F, Carabellese N, VillanacciV,et al., High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of Celiac disease. Dig Liver Dis 2012; 44: 280-5.
19. Fernández ML, Vivas S, Ruiz de Morales JM, Marugan JM. Usefulness of anti-transglutaminase antibodies in the diagnosis of Celiac disease.GastroenterolHepatol 2005; 28: 437-40.
20. Abrams JA, Brar P, Diamond B, Rotterdam H, Green PH. Utility in clinical practice of immunoglobulin a anti-tissue transglutaminase antibody for the diagnosis of Celiac disease. ClinGastroenterolHepatol 2006; 4: 726-730.
21. Vivas S, Ruiz de Morales JG, Riestra S, Arias L, Fuentes D, Alvarez N, et al. Duodenal biopsy may be avoided when high transglutaminase antibody titers are present.World J Gastroenterol 2009; 15:4775-80.
Published
2019-03-17
Issue
Section
Original Article
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).
