Abstract
Recently, the endomysial antigen has been identified as the protein cross‐linking enzyme known as tissue transglutaminase (tTG). Our objective was to compare a novel enzyme immunoassay (EIA) that detects IgA antibody against tTG to two standard IFA methods utilizing thin tissue sections of rat kidney/rat stomach (KS) and distal primate esophagus (PE) as substrates to detect IgA antibody against endomysium (EMA). Sera from 100 patients suspected of having gluten‐sensitive enteropathy (GSE) and 23 sera possessing various antibodies used for EIA cross‐reactivity studies were included. Additional tests, performed routinely in our laboratory, were utilized to further assess sera from patients suspected having GSE. These tests include anti‐gliadin IgA antibody (AGA) and anti‐reticulin IgA antibody (ARA) and are part of the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN) revised criteria for diagnosing GSE. When compared to IFA using KS, the tTG EIA had a sensitivity of 87.5%, was 97.1% specific, and had an overall agreement of 94.0%. When compared to IFA using PE, the tTG EIA had a sensitivity of 92.6%, was 93.2% specific, and had an overall agreement of 93.0%. When the KS IFA was compared to the PE IFA for EMA, the KS IFA had a sensitivity of 96.3%, was 91.8% specific, and had an overall agreement of 93.0%. The majority of sera that were positive for tTG but were negative by IFA (KS, n = 2/PE, n = 5) possessed IgA antibodies against gliadin and/or reticulin. Five of six sera with negative results by PE IFA were positive by the KS IFA and possessed one or more antibodies to tTG and/or gliadin and/or reticulin. We conclude that the tTG EIA compares well to both KS and PE IFAs when detecting IgA antibody against endomysium. We do not recommend the use of PE to detect EMA primarily because of the inconsistencies (i.e., tissue selection, quality, and preparation) and limited availability of commercially prepared PE tissue. J. Clin. Lab. Anal. 15:108–111, 2001. © 2001 Wiley‐Liss, Inc.
Keywords: celiac disease, IgA, tTG, gluten‐sensitive enteropathy, dermatitis herpetiformis, gliadin, reticulin, EMA, IFA, EIA
REFERENCES
- 1. Meeuwisse GW. 1970. Diagnostic criteria in coeliac disease. Acta Paediatr Scand 59:461. [Google Scholar]
- 2. Walker‐Smith JA, Guandalini S, Schmitz J, Shmerling DH, Visakorpi JK. 1990. Revised criteria for diagnosis of coeliac disease: report of working group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 65:909–911. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Marsh MN. 1997. Transglutaminase, gluten and celiac disease: food for thought. Nat Med 3:725–726. [DOI] [PubMed] [Google Scholar]
- 4. Chorzelski TP, Beutner EH, Sulej J, et al. 1984. IgA anti‐endomysium antibody. A new immunological marker of dermatitis herpetiformis and coeliac disease. Br J Dermatol III: 395–402. [DOI] [PubMed] [Google Scholar]
- 5. Grodzinsky E, Hed J, Skogh T. 1994. IgA antiendomysium antibodies have a high positive predictive value for celiac disease in asymptomatic patients. Allergy 49:593–597. [DOI] [PubMed] [Google Scholar]
- 6. Chorzelski TP, Beutner EH, Zalewski TK, et al, editors. 1990. Serological diagnosis of coeliac disease. Boca Raton, FL: CRC Press. [Google Scholar]
- 7. Dieterich W, Ehnis T, Bauer M, et al. 1997. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 3:797–801. [DOI] [PubMed] [Google Scholar]
- 8. Chorzelski TP, Sulej J, Tchorzewska H, et al. 1983. IgA class antibodies in dermatitis herpetiformis and coeliac disease. Ann NY Acad Sci 420:325–334. [DOI] [PubMed] [Google Scholar]
- 9. Volta U, Molinaro N, De Franchis R, et al. 1992. Correlation between IgA antiendomysial antibodies and subtotal villous atrophy in dermatitis herpetiformis. J Clin Gastroenterol 14:298–301. [DOI] [PubMed] [Google Scholar]
- 10. Volta U, Molinaro N, Fusconi M, Cassani F, Bianchi FB. 1991. IgA antiendomysial antibody test. A step forward in celiac disease screening. Digest Dis Sci 36:752–756,. [DOI] [PubMed] [Google Scholar]
- 11. Sategna‐Guidetti C, Pulitano R, Grosso S, Ferfoglia G. 1993. Serum IgA antiendomysium antibody titers as a marker of intestinal involvement and diet compliance in adult celiac sprue. J Clin Gastroenterol 17:123–127. [DOI] [PubMed] [Google Scholar]
- 12. Valdimarsson T, Franzen L, Grodzinsky E, Skogh T, Strom M. 1996. Is small bowel biopsy necessary in adults with suspected celiac disease and IgA anti‐endomysium antibodies? 100% positive predictive value for celiac disease in adults. Digest Dis Sci 41:83–87. [DOI] [PubMed] [Google Scholar]
- 13. Unsworth DJ. 1996. Serological diagnosis of gluten sensitive enteropathy. J Clin Pathol 49:704–711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Lock RJ, Pitcher MC, Unsworth DJ. 1999. IgA anti‐tissue transglutaminase as a diagnostic marker of gluten sensitive enteropathy. J Clin Pathol 52:274–277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Dieterich W, Laag E, Bruckner‐Tuderman L, et al. 1999. Antibodies to tissue transglutaminase as a serologic markers in patients with dermatitis herpetiformis. J Invest Dermatol 113:133–136,. [DOI] [PubMed] [Google Scholar]
- 16. Miller A, Paspaliaris W, Elliot PR, d’Apice A. 1999. Anti‐transglutaminase antibodies and coeliac disease. Aust NZ J Med 29:239–242. [DOI] [PubMed] [Google Scholar]
- 17. Dieterich W, Laag E, Schopper H, et al. 1998. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 115:1317–1321. [DOI] [PubMed] [Google Scholar]
- 18. Troncone R, Maurano F, Rossi M, et al. 1999. IgA antibodies to tissue transglutaminase: an effective diagnostic test for celiac disease. J Pediatr 134:166–171. [DOI] [PubMed] [Google Scholar]