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. 1984 Nov 1;160(5):1544–1557. doi: 10.1084/jem.160.5.1544

Possible role for a human adenovirus in the pathogenesis of celiac disease

PMCID: PMC2187489  PMID: 6491604

Abstract

Celiac disease in humans is activated by the dietary ingestion of wheat, rye, triticale, barley, and possibly oats. Gliadins in wheat and similar proteins in the other grains are known to activate disease in susceptible individuals. There is a striking association between celiac disease and HLA-B8, -DR3 and/or -DR7, and -DC3. Nonetheless, less than 0.2% of individuals with those serologic HLA specificities develop celiac disease and disease is not always concordant among monozygotic twins. We propose that additional environmental factors may be important in the pathogenesis of celiac disease. To investigate that possibility, we examined a data bank of protein sequences for other proteins that might share amino acid sequence homologies with A- gliadin, an alpha-gliadin component known to activate celiac disease and whose complete primary amino acid sequence is known. These studies demonstrate that A-gliadin shares a region of amino acid sequence homology with the 54-kD E1b protein of human adenovirus type 12 (Ad12), an adenovirus usually isolated from the intestinal tract. The region spans 12 amino acid residues, includes 8 residue identities and an identical pentapeptide, and is hydrophilic in both proteins. Antibody reactive with the 54-kD Ad12 E1b protein cross-reacts with A-gliadin, a 119 amino acid cyanogen bromide peptide of A-gliadin that spans the region of homology and a synthetic heptapeptide of A-gliadin from within the region of homology. We suggest that an encounter of the immune system with antigenic determinants produced during intestinal viral infection may be important in the pathogenesis of celiac disease.

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Selected References

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  1. Albert E. D., Harms K., Wank R., Steinbauer-Rosenthal I., Scholz S. Segregation analysis of HL-A antigens and haplotypes in 50 families of patients with coeliac disease. Transplant Proc. 1973 Dec;5(4):1785–1789. [PubMed] [Google Scholar]
  2. Bernards R., Schrier P. I., Houweling A., Bos J. L., van der Eb A. J., Zijlstra M., Melief C. J. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. 1983 Oct 27-Nov 2Nature. 305(5937):776–779. doi: 10.1038/305776a0. [DOI] [PubMed] [Google Scholar]
  3. Bruck C., Portetelle D., Glineur C., Bollen A. One-step purification of mouse monoclonal antibodies from ascitic fluid by DEAE Affi-Gel blue chromatography. J Immunol Methods. 1982 Sep 30;53(3):313–319. doi: 10.1016/0022-1759(82)90178-8. [DOI] [PubMed] [Google Scholar]
  4. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  5. CARTER C., SHELDON W., WALKER C. The inheritance of coeliac disease. Ann Hum Genet. 1959 Jul;23:266–278. doi: 10.1111/j.1469-1809.1959.tb01470.x. [DOI] [PubMed] [Google Scholar]
  6. Chou P. Y., Fasman G. D. Empirical predictions of protein conformation. Annu Rev Biochem. 1978;47:251–276. doi: 10.1146/annurev.bi.47.070178.001343. [DOI] [PubMed] [Google Scholar]
  7. Doolittle R. F. Similar amino acid sequences: chance or common ancestry? Science. 1981 Oct 9;214(4517):149–159. doi: 10.1126/science.7280687. [DOI] [PubMed] [Google Scholar]
  8. Ek J., Albrechtsen D., Solheim B. G., Thorsby E. Strong association between the HLA-Dw3-related B cell alloantigen -DRw3 and coeliac disease. Scand J Gastroenterol. 1978;13(2):229–233. doi: 10.3109/00365527809181753. [DOI] [PubMed] [Google Scholar]
  9. Falchuk Z. M., Gebhard R. L., Sessoms C., Strober W. An in vitro model of gluten-sensitive enteropathy. Effect of gliadin on intestinal epithelial cells of patients with gluten-sensitive enteropathy in organ culture. J Clin Invest. 1974 Feb;53(2):487–500. doi: 10.1172/JCI107582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Falchuk Z. M., Rogentine G. N., Strober W. Predominance of histocompatibility antigen HL-A8 in patients with gluten-sensitive enteropathy. J Clin Invest. 1972 Jun;51(6):1602–1605. doi: 10.1172/JCI106958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Falchuk Z. M. Update on gluten-sensitive enteropathy. Am J Med. 1979 Dec;67(6):1085–1096. doi: 10.1016/0002-9343(79)90651-x. [DOI] [PubMed] [Google Scholar]
  12. Hoffman H. N., 2nd, Wollaeger E. E., Greenberg E. Discordance for nontropical sprue (adult celiac disease) in a monozygotic twin pair. Gastroenterology. 1966 Jul;51(1):36–42. [PubMed] [Google Scholar]
  13. Kagnoff M. F., Austin R. K., Johnson H. C., Bernardin J. E., Dietler M. D., Kasarda D. D. Celiac sprue: correlation with murine T cell responses to wheat gliadin components. J Immunol. 1982 Dec;129(6):2693–2697. [PubMed] [Google Scholar]
  14. Kasarda D. D., Okita T. W., Bernardin J. E., Baecker P. A., Nimmo C. C., Lew E. J., Dietler M. D., Greene F. C. Nucleic acid (cDNA) and amino acid sequences of alpha-type gliadins from wheat (Triticum aestivum). Proc Natl Acad Sci U S A. 1984 Aug;81(15):4712–4716. doi: 10.1073/pnas.81.15.4712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kimura T., Sawada Y., Shinawawa M., Shimizu Y., Shiroki K., Shimojo H., Sugisaki H., Takanami M., Uemizu Y., Fujinaga K. Nucleotide sequence of the transforming early region E1b of adenovirus type 12 DNA: structure and gene organization, and comparison with those of adenovirus type 5 DNA. Nucleic Acids Res. 1981 Dec 11;9(23):6571–6589. doi: 10.1093/nar/9.23.6571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  17. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  18. Mak S., Mak I., Smiley J. R., Graham F. L. Tumorigenicity and viral gene expression in rat cells transformed by Ad 12 virions or by the EcoRI c fragment of Ad 12 DNA. Virology. 1979 Oct 30;98(2):456–460. doi: 10.1016/0042-6822(79)90568-3. [DOI] [PubMed] [Google Scholar]
  19. Perricaudet M., le Moullec J. M., Tiollais P., Pettersson U. Structure of two adenovirus type 12 transforming polypeptides and their evolutionary implications. Nature. 1980 Nov 13;288(5787):174–176. doi: 10.1038/288174a0. [DOI] [PubMed] [Google Scholar]
  20. Peña A. S., Mann D. L., Hague N. E., Heck J. A., van Leeuwen H. A., van Rood J. J., Strober W. Genetic basis of gluten-sentitive enteropathy. Gastroenterology. 1978 Aug;75(2):230–235. [PubMed] [Google Scholar]
  21. Rood J. J., Hooff J. P., Keuning J. J. Disease predisposition, immune responsiveness and the fine structure of the HL-A supergene. A need for a reappraisal. Transplant Rev. 1975;22:75–104. doi: 10.1111/j.1600-065x.1975.tb01552.x. [DOI] [PubMed] [Google Scholar]
  22. Schrier P. I., Bernards R., Vaessen R. T., Houweling A., van der Eb A. J. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. 1983 Oct 27-Nov 2Nature. 305(5937):771–775. doi: 10.1038/305771a0. [DOI] [PubMed] [Google Scholar]
  23. Stokes P. L., Asquith P., Holmes G. K., Mackintosh P., Cooke W. T. Histocompatibility antigens associated with adult coeliac disease. Lancet. 1972 Jul 22;2(7769):162–164. doi: 10.1016/s0140-6736(72)91330-x. [DOI] [PubMed] [Google Scholar]
  24. Swinson C. M., Slavin G., Coles E. C., Booth C. C. Coeliac disease and malignancy. Lancet. 1983 Jan 15;1(8316):111–115. doi: 10.1016/s0140-6736(83)91754-3. [DOI] [PubMed] [Google Scholar]
  25. Tosi R., Vismara D., Tanigaki N., Ferrara G. B., Cicimarra F., Buffolano W., Follo D., Auricchio S. Evidence that celiac disease is primarily associated with a DC locus allelic specificity. Clin Immunol Immunopathol. 1983 Sep;28(3):395–404. doi: 10.1016/0090-1229(83)90106-x. [DOI] [PubMed] [Google Scholar]
  26. Trefts P. E., Kagnoff M. F. Gluten-sensitive enteropathy. I. The T-dependent anti-A-gliadin antibody response maps to the murine major histocompatibility locus. J Immunol. 1981 Jun;126(6):2249–2252. [PubMed] [Google Scholar]
  27. Walker-Smith J. A. Discordance for childhood coeliac disease in monozygotic twins. Gut. 1973 May;14(5):374–375. doi: 10.1136/gut.14.5.374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Walter G., Hutchinson M. A., Hunter T., Eckhart W. Antibodies specific for the polyoma virus middle-size tumor antigen. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4882–4886. doi: 10.1073/pnas.78.8.4882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Walter G., Scheidtmann K. H., Carbone A., Laudano A. P., Doolittle R. F. Antibodies specific for the carboxy- and amino-terminal regions of simian virus 40 large tumor antigen. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5197–5200. doi: 10.1073/pnas.77.9.5197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Weiss J. B., Austin R. K., Schanfield M. S., Kagnoff M. F. Gluten-sensitive enteropathy. Immunoglobulin G heavy-chain (Gm) allotypes and the immune response to wheat gliadin. J Clin Invest. 1983 Jul;72(1):96–101. doi: 10.1172/JCI110988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wilson M. C., Fraser N. W., Darnell J. E., Jr Mapping of RNA initiation sites by high doses of uv irradiation: evidence for three independent promoters within the left 11% of the Ad-2 genome. Virology. 1979 Apr 15;94(1):175–184. doi: 10.1016/0042-6822(79)90447-1. [DOI] [PubMed] [Google Scholar]

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