Abstract
Celiac disease (CD) is a malabsorptive disorder of the small intestine characterized by villous atrophy, hyperplastic crypts and T cell infiltration in the epithelium and in the lamina propria [1]. The disease is caused by an abnormal immune response to gluten, probably initiated by the activation of T cells in the intestinal mucosa to gluten-derived peptides. CD is strongly associated to specific genes in the HLA complex and is a unique model for studies of type 1 diabetes and other HLA associated diseases since (a) the primary HLA associations have been established, (b) the disease-inducing agent (gluten) is known and (c) gluten-specific T cells from the target organ, the intestinal mucosa, are accessible from biopsies for in vitro studies.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Trier, J.S. (1991) Celiac sprue, N. Engl. J. Med. 325 1709–1719.
Polanco, I., Biemond, I., van Leeuwen et al. (1981) Gluten senstitive enteropathy in Spain: genetic and environmental factors, in: McConnell, R.B. (Ed.) The genetics of coeliac disease, Lancaster: MTB, 211–31.
Mearin, M.L., Biemond, I., Peña, A.S. et al. (1983) HLA-DR phenotypes in Spanish coeliac children: their contribution to the understanding of the genetics of the disease, Gut 24 532–537.
Hernández, J.L., Michalski, J.P., McCombs, C.C. et al. (1991) Evidence for a dominant gene mechanism underlying coeliac disease in the West of Ireland, Genetic Epidemiol. 8 13–27.
Thorsby, E. (1995) HLA-associated disease susceptibility. - Which genes are primarily involved? The Immunologist 3 51.
Zhong, F., McCombs, C.C., Olson, J.M. et al. (1996) An autosomal screen for genes that predispose to celiac disease in the western countries of Ireland, Nature Gen. 14 329–333.
Sollid, L.M. and Thorsby, E. (1993) HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis, Gastroenterology 105 910–922.
Sollid, L.M., Markussen, G., Ek, J., Gjerde, H. et al. (1989) Evidence for a primary association of celiac disease to a particular HLA-DQ α/β heterodimer, J. Exp. Med. 169345–350.
Spurkland, A., Sollid, L.M., Ronningen, K.S. et al. (1990) Susceptibility to develop celiac disease is primarily associated with HLA-DQ alleles, Human Immunology 29 157–165.
Halstensen, T.S., Scott, H., Fausa, O. and Brandtzaeg, P. (1993) Glutens stimulation of coeliac mucosa in vitro induces activation (CD25) of lamina propria CD4+ T cells and macrophages but no crypt-cell hyperplasia, Scand. J. Immunol. 38 581–590.
Lundin, K.E.A., Scott, H., Hansen, T. et al. (1993) Gliadin specific, HLA-DQ2 restricted T cells isolated from the small intestinal mucosa of celiac disease patients, J. Exp. Med. 178 187–196.
Lundin, K.E.A., Scott, H., Fausa, O. et al. (1994) T cells from the small intestinal mucosa of a DR4,DQ7/DR4,DQ8 celiac disease patient preferentially recognize gliadin presented by DQ8, Human Immunology 41 285–291.
Gjertsen, H.A., Sollid, L.M., Ek, J., Thorsby, E. and Lundin, K.E.A. (1994) Both HLA-DR, -DQ, and -DP restricted gluten-specific T cell clones can be isolated from the peripheral blood of celiac disease patients, Scand. J. Immunol. 39 567–574.
Jensen, K., Sollid, L.M., Scott, H. et al. (1995) Gliadin-specific T cell responses in peripheral blood of healthy individuals involve T cells restricted by the coeliac disease associated DQ2 heterodimer, Scand. J. Immunol. 42 166–170.
Nilsen, E.M., Lundin, K.E.A., Krajci, P. et al. (1995) Gluten-specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Thl or Th0 profile dominated by interferon γ, Gut 37 6–76.
Lundin, K.E.A., Sollid, L.M., Anthonsen, D., Norén, O., Molberg, Ø.,Thorsby, E. and Sjöström, H. (1997) Heterogeneous reactivity patterns of HLA-DQ restricted, small intestinal T-cell clones from celiac disease patients, Gastroentrology, (In Press).
Johansen, B.H., Vartdal, F., Eriksen, J.A. et al. (1996) Identification of a putative motif for binding of peptides to HLA-DQ2, Int. Immunol. 8 177–182.
Vartdal, F., Johansen, B.H., Friede, T. et al. (1996) The peptide binding motif of the disease associated HLA-DQ (α1*0501, β1*0201) molecule, Eur. J. Immunol. 26 2764–2772.
Sugiyama, T., Rafalski, A. and Söll, D. (1986) The nucletide sequence of a wheat 7-gliadin genomic clone, Plant Sci. 44 205–209.
Picarelli, A., Maiuri, L., Frate, A. et al. (1996) Production of antiendomycial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with celiac disease, Lancet 348 1065–1067.
Sercarz, E.E. and Datta, S.K. (1994) Autoimmunity. Editorial overview, Curr. Op. Immunol. 6 875–877.
Wicker, L. and Wekerle, H. (1995) Autoimmunity. Editorial overview, Curr. Op. Immunol. 7, 783–785.
Aichele, P., Bachmann, M.F., Hengartner, H. and Zinkernagel, R.M. (1966) Immunopahtology or organ-specific autoimmunity as a consequence of virus infection, Imm. Rev. 152 21–45.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Sollid, L.M. et al. (1997). The Molecular Basis of the HLA Association in Celiac Disease. In: Madrigal, A.J., Bencová, M., Middleton, D., Charron, D., Nánási, T. (eds) Immunogenetics: Advances and Education. NATO ASI Series, vol 35. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5486-4_7
Download citation
DOI: https://doi.org/10.1007/978-94-011-5486-4_7
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-6308-1
Online ISBN: 978-94-011-5486-4
eBook Packages: Springer Book Archive