Gastroenterology
Volume 129, Issue 4 , Pages 1294-1301 , October 2005

Celiac Disease: Caught Between a Rock and a Hard Place

  • Frits Koning

      Affiliations

    • Corresponding Author InformationAddress requests for reprints to: Frits Koning, PhD, Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, E3-Q, PO Box 9600, 2300 RC Leiden, The Netherlands.fax: (31) 71-5216751.

Received 7 January 2005 ,Accepted 8 April 2005.

References 

  1. Catassi C, Ratsch IM, Fabiani E, Rossini M, Bordicchia F, Candela F, et al. Coeliac disease in the year 2000 (exploring the iceberg) . Lancet . 1994;343:200–203
  2. Rostami K, Mulder CJ, Werre JM, van Beukelen FR, Kerchhaert J, Crusius JB, et al. High prevalence of celiac disease in apparently healthy blood donors suggests a high prevalence of undiagnosed celiac disease in the Dutch population . Scand J Gastroenterol . 1999;34:276–279
  3. Csizmadia CGDS , Mearin MKL , von Blomberg BMW , Brand R , Verloove-Vanhorick SP . An iceberg of childhood coeliac disease in the Netherlands . Lancet . 1999;353:813–814
  4. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States (a large multicenter study) . Arch Intern Med . 2003;163:286–292
  5. Sollid LM , Markussen G , Ek J , Gjerde H , Vartdal F , Thorsby E . Evidence for a primary association of coeliac disease to a particular HLA-DQ alpha/beta heterodimer . J Exp Med . 1989;169:345–350
  6. Spurkland A , Ingvarsson G , Falk ES , Knutsen I , Sollid LM , Thorsby E . Dermatitis herpetiformis and celiac disease are both primarily associated with the HLA-DQ (alpha 1*0501, beta 1*02) or the HLA-DQ (alpha 1*03, beta 1*0302) heterodimers . Tissue Antigens . 1997;49:29–34
  7. Lundin KE, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O, et al. Gliadin-specific, HLA-DQ(α1*0501,β1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients . J Exp Med . 1993;178:187–196
  8. Lundin KA , Scott H , Fausa O , Thorsby E , Sollid LM . T cells from the small intestinal mucosa of a DR4, DQ7/DR4, DQ8 celiac-disease patient preferentially recognize gliadin when presented by DQ8 . Hum Immunol . 1994;41:285–291
  9. van de Wal Y, Kooy Y, van Veelen P, Pena S, Mearin L, Molberg Ø, et al. Small intestinal cells of celiac disease patients recognize a natural pepsin fragment of gliadin . Proc Natl Acad Sci U S A . 1998;95:10050–10054
  10. Sjostrom H, Lundin KEA, Molberg Ø, Korner R, McAdam S, Anthonsen D, et al. Identification of a gliadin T cell epitope in coeliac disease (general importance of gliadin deamidation for intestinal T cell recognition) . Scand J Immunol . 1998;48:111–115
  11. van de Wal Y , Kooy YMC , van Veelen P , August SA , Drijfhout JW , Koning F . Glutenin is involved in the gluten-driven mucosal T cell response . Eur J Immunol . 2000;29:3133–3139
  12. Arentz-Hansen H, Körner R, Molberg Ø, Quarsten H, Vader W, Kooy YMC, et al. The intestinal T cell response to α-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase . J Exp Med . 2000;191:603–612
  13. Anderson RP , Degano P , Godkin AJ , Jewell DP , Hill AV . In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope . Nat Med . 2000;6:337–342
  14. Kim CY , Quarsten H , Bergseng E , Khosla C , Sollid LM . Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease . Proc Natl Acad Sci U S A . 2004;101:4175–4179
  15. Molberg Ø, McAdam S, Körner R, Quarsten H, Kristiansen C, Madsen L, et al. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut derived T cells in celiac disease . Nat Med . 1998;4:713–717
  16. van de Wal Y, Kooy YMC, van Veelen P, Peña AS, Mearin ML, Papadopoulos GK, et al. Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity . J Immunol . 1998;161:1585–1588
  17. Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease . Nat Med . 1997;3:797–801
  18. Hüe S, Mention J-J, Monteiro RC, Zhang SL, Cellier C, Schmitz J, et al. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease . Immunity . 2004;21:367–377
  19. Meresse B, Chen Z, Ciszewski C, Tretiakova M, Bhagat G, Krausz TN, et al. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease . Immunity . 2004;21:357–366
  20. Reif S , Lerner A . Tissue transglutaminase—the key player in celiac disease (a review) . Autoimmunity Rev . 2004;3:40–45
  21. Dicke WK . Coeliakie . In: Unpublished thesis . The Netherlands: University of Utrecht; 1950;
  22. Shewry PR , Tatham AS . The prolamin storage proteins of cereal seeds (structure and evolution) . Biochem J . 1990;267:1–12
  23. Mearin ML, Biemond I, Pena A, Polanco I, Vazquez C, Schreuder GT, et al. HLA-DR phenotypes in Spanish coeliac children (their contribution to the understanding of the genetics of the disease) . Gut . 1983;24:532–537
  24. Sollid LM . Coeliac disease (dissecting a complex inflammatory disorder) . Nat Rev Immunol . 2002;2:647–655
  25. van de Wal Y , Kooy YMC , Drijfhout JW , Amons R , Koning F . Peptide binding characteristics of the coeliac disease-associated DQ(α1*0501,β1*0201) molecule . Immunogenetics . 1996;44:246–253
  26. Johansen BH , Vartdal F , Eriksen JA , Thorsby E , Sollid LM . Identification of a putative motif for binding of peptides to HLA-DQ2 . Int Immunol . 1996;8:177–182
  27. Kwok WW , Domeier ME , Raymond FC , Byers P , Nepom GT . Allele-specific motifs characterize HLA-DQ interactions with a diabetes-associated peptide derived from glutamic acid decarboxylase . J Immunol . 1996;156:2171–2177
  28. Molberg Ø, McAdam S, Lundin KEA, Kristiansen C, Arentz-Hansen H, Kett K, et al. T cells from celiac-disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase . Eur J Immunol . 2001;31:1317–1323
  29. Fleckenstein B, Molberg O, Qiao SW, Schmid DG, von der Mulbe F, Elgstoen K, et al. Gliadin T cell epitope selection by tissue transglutaminase in celiac disease (Role of enzyme specificity and pH influence on the transamidation versus deamidation process) . J Biol Chem . 2002;277:34109–34116
  30. Vader W, Kooy Y, van Veelen P, de Ru A, Harris D, Benckhuijsen W, et al. The gluten response in children with recent onset celiac disease (A highly diverse response towards multiple gliadin and glutenin derived peptides) . Gastroenterology . 2002;122:1729–1737
  31. Vader W, de Ru A, van de Wal Y, Kooy Y, Benckhuijsen W, Mearin L, et al. Specificity of tissue transglutaminase explains cereal toxicity in celiac disease . J Exp Med . 2002;195:643–649
  32. Molberg Ø, Flaete NS, Jensen T, Lundin KEA, Arentz-Hansen H, Anderson OD, et al. Intestinal T-cell responses to high-molecular-weight glutenins in celiac disease . Gastroenterology . 2003;125:337–344
  33. Arentz-Hansen H, McAdam SN, Molberg Ø, Fleckenstein B, Lundin KEA, Jorgensen TJ, et al. Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues . Gastroenterology . 2002;123:803–809
  34. Shan L, Molberg Ø, Parrot I, Hausch F, Filiz F, Gray GM, et al. Structural basis for gluten intolerance in celiac sprue . Science . 2002;297:2275–2279
  35. Janatuinen EK, Pikkarainen PH, Kemppainen TA, Kosma V-M, Järvinen RMK, Uusitupa MIJ, et al. A comparison of diets with and without oats in adults with celiac disease . N Engl J Med . 1995;333:1033–1037
  36. Vader W, Stepniak D, Bunnik EM, Kooy Y, de Haan W, Drijfhout JW, et al. Characterization of cereal toxicity for celiac disease patients based on protein homology in grains . Gastroenterology . 2003;125:1105–1113
  37. Arentz-Hansen H, Fleckenstein B, Molberg O, Scott H, Koning F, Jung G, et al. The molecular basis for oat intolerance in patients with celiac disease . PLoS Med . 2004;1:84–92
  38. Vader W, Stepniak D, Kooy Y, Mearin ML, Thompson A, Spaenij L, et al. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T-cell responses . Proc Natl Acad Sci U S A . 2003;100:12390–12395
  39. Sturgess R, Day P, Ellis HJ, Lundin KE, Gjertsen HA, Kontakou M, et al. Wheat peptide challenge in coeliac disease . Lancet . 1994;343:758–761
  40. Shidrawi RG , Day P , Przemioslo R , Ellis HJ , Nelufer JM , Ciclitira PJ . In vitro toxicity of gluten peptides in coeliac disease assessed by organ culture . Scand J Gastroenterol . 1995;30:758–763
  41. Maiuri L, Troncone R, Mayer M, Coletta S, Picarelli A, De Vincenzi M, et al. In vitro activities of A-gliadin–related synthetic peptides (damaging effect on the atrophic coeliac mucosa and activation of mucosal immune response in the treated coeliac mucosa) . Scand J Gastroenterol . 1996;31:247–253
  42. Jelínková L , Tuková L , Cinová J , Flegelová Z , Tlaskalová-Hogenová H . Gliadin stimulates human monocytes to production of IL-8 and TNF-α through a mechanism involving NF-κB . FEBS Lett . 2004;571:81–85
  43. Maiuri L, Ciacci C, Ricciardelli I, Vacca L, Raia V, Auricchio S, et al. Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease . Lancet . 2003;362:30–37
  44. Maiuri L , Ciacci C , Auricchio S , Brown V , Quaratino S , Londei M . Interleukin 15 mediates epithelial changes in celiac disease . Gastroenterology . 2000;119:996–1006
  45. Maki M , Collin P . Coeliac disease . Lancet . 1997;349:1755–1759
  46. Sollid LM , Molberg Ø , McAdam S , Lundin KEA . Autoantibodies in coeliac disease (tissue transglutaminase-guilt by association?) . Gut . 1997;41:851–852
  47. Fleckenstein B , Qiao SW , Larsen MR , Jung G , Roepstorff P , Sollid LM . Molecular characterization of covalent complexes between tissue transglutaminase and gliadin peptides . J Biol Chem . 2004;279:17607–17616
  48. Bardella MT , Marino R , Meroni PL . Celiac disease during interferon treatment . Ann Intern Med . 1999;131:157–158
  49. Cammarota G , Cuoco L , Cianci R , Pandolfi F , Gasbarrini G . Onset of coeliac disease during treatment with interferon for chronic hepatitis C . Lancet . 2000;356:1494–1495
  50. Monteleone G , Pender SLF , Alstead E , Hauer AC , Lionetti P , MacDonald TT . Role of interferon in promoting T helper cell type 1 responses in the small intestine in coeliac disease . Gut . 2001;48:425–429
  51. Holopainen P, Arvas M, Sistonen P, Mustalahti K, Collin P, Maki M, et al. CD28/CTLA4 gene region on chromosome 2q33 confers genetic susceptibility to celiac disease (A linkage and family-based association study) . Tissue Antigens . 1999;53:470–475
  52. Naluai AT, Nilsson S, Samuelsson L, Gudjonsdottir AH, Ascher H, Ek J, et al. The CTLA4/CD28 gene region on chromosome 2q33 confers susceptibility to celiac disease in a way possibly distinct from that of type 1 diabetes and other chronic inflammatory disorders . Tissue Antigens . 2000;56:350–355
  53. Rioux JD, Karinen H, Kocher K, McMahon SG, Karkkainen P, Janatuinen E, et al. Genome-wide search and association studies in a Finnish celiac disease population (identification of a novel locus and replication of the HLA and CTLA4 loci) . Am J Med Genet . 2004;130:345–350
  54. Zhong F, McCombs CC, Olson JM, Elston RC, Stevens FM, McCarthy CF, et al. An autosomal screen for genes that predispose to celiac disease in the western counties of Ireland . Nat Genet . 1996;14:329–333
  55. Greco L, Corazza G, Babron MC, Clot F, Fulchignoni-Lataud M-C, Percopo S, et al. Genome search in celiac disease . Am J Hum Genet . 1998;62:669–675
  56. van Belzen MJ, Meijer JWR, Sandkuijl LA, Bardoel AFJ, Mulder CJJ, Pearson PL, et al. A major non-HLA locus in celiac disease maps to chromosome 19 . Gastroenterology . 2003;125:1032–1041
  57. Ivarsson A, Persson LȦ, Nyström L, Ascher H, Cavell B, Danielsson L, et al. Epidemic of coeliac disease in Swedish children . Acta Paediatr . 2000;89:165–171
  58. Norris JM, Barriga K, Klingensmith G, Hoffman M, Eisenbarth GS, Erlich HA, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity . JAMA . 2003;290:1713–1720
  59. Ziegler AG , Schmid S , Huber D , Hummel M , Bonifacio E . Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies . JAMA . 2003;290:1721–1728
  60. Spaenij-Dekking EHA , Kooy-Winkelaar EMC , Drijfhout JW , Koning F . A novel and sensitive method for the detection of T cell stimulatory epitopes of α/β- and γ- gliadin . Gut . 2004;53:1267–1273
  61. Stepniak D, Vader WL, Kooy Y, van Veelen PA, Moustakas A, Papandreou NA, et al. T cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1 . Immunogenetics . 2005;57:8–15

 Supported by grants from the European Commission (BHM4-CT98-3087 and QLK1-2000-00657), the “Stimuleringsfonds Voedingsonderzoek Leiden University Medical Centre,” the Dutch Organization for Scientific Research (ZonMW grant 912-02-028), and the Celiac Disease Consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK03009).

PII: S0016-5085(05)01430-7

doi: 10.1053/j.gastro.2005.07.030

Gastroenterology
Volume 129, Issue 4 , Pages 1294-1301 , October 2005

Article Tools

* Image Usage & Resolution