Therapie und Management der Zöliakie/einheimischen Sprue

Zusammenfassung

Nach Diagnosestellung und Einhaltung einer glutenfreien Diät verläuft eine Zöliakie bei der Mehrzahl der Patienten meist unproblematisch. Dennoch kann es in seltenen Fällen zu schweren Komplikationen, wie z. B. einer refraktären Zöliakie oder einem Lymphom, kommen. Weiterhin können die Verlaufsformen der Zöliakie sehr heterogen sein, welches eine differenzierte Betreuung erfordert. So ist es umstritten, inwiefern asymptomatische Patienten, die die typischen Schleimhautveränderungen aufweisen, eine glutenfreie Diät einhalten sollen. Ein großes Problem stellen auch bewusste oder unbewusste Diätfehler dar. Zudem ist eine 100 %ige „glutenfreie” Diät überhaupt nicht möglich, da viele Nahrungsmittel geringe Verunreinigungen an Gluten enthalten, die glücklicherweise von den allermeisten Patienten gut toleriert werden. Erschwerend kommt hinzu, dass die Toleranzschwelle gegenüber Restmengen an Gluten sehr unterschiedlich sein kann. Bei der Betreuung der Patienten hat deshalb die Überwachung einer glutenfreien Diät bzw. das rechtzeitige Erkennen von Komplikationen einen zentralen Stellenwert. Auf die Rolle der Antikörperbestimmung und der Histologie zur Verlaufskontrolle wird deshalb in dieser Übersicht ausführlich eingegangen.

Abstract

In most patients the clinical course of celiac disease is unproblematic after the diagnosis has been made and a strict gluten-free diet is established. However, in rare cases complications like refractory sprue or lymphoma can occur. Individual management is required since the clinical presentation of celiac disease can be very heterogeneous. For example, it is a matter of controversy if asymptomatic patients, who have the same typical histological changes in their small bowel like patients with symptomatic celiac disease, should adhere to a gluten-free diet. A major problem is the compliance and the unintentional intake of gluten. A 100 % gluten-free diet is not possible since most food components are contaminated with trace amounts of gluten. Fortunately most patients tolerate these contaminations. Furthermore, the threshold for gluten contamination can differ highly among patients. One central point in patient care is the monitoring of a gluten-free diet and the timely recognition of complications. Therefore, the role of antibodies and duodenal histology in monitoring the course of the disease will be discussed.

Schlüsselwörter

Zöliakie - Sprue - Management - Therapie - Komplikationen

Key words

celiac disease - coeliac disease - management - complications

Literatur

• 1 Holtmeier W. Diagnosis of celiac disease.  Z Gastroenterol. 2005;  43 1243-1252
• 2 Holtmeier W, Henker J, Riecken E O. et al . Verlaufsformen und Definitionen der Zöliakie - Stellungnahme einer Expertengruppe der Deutschen Zöliakie-Gesellschaft.  Z Gastroenterol. 2005;  43 751-754
• 3 Holtmeier W, Caspary W F. Celiac disease.  Orphanet Journal of Rare Diseases. 2006;  I 3 , http://www.ojrd.com/content/1/1/3
• 4 Abdulkarim A S, Burgart L J, See J. et al . Etiology of nonresponsive celiac disease: Results of a systematic approach.  Am J Gastroenterol. 2002;  97 2016-2021
• 5 Kupper C. Dietary guidelines and implementation for celiac disease.  Gastroenterology. 2005;  128 S121-S127
• 6 Collin P, Thorell L, Kaukinen K. et al . The safe threshold for gluten contamination in gluten-free products. Can trace amounts be accepted in the treatment of coeliac disease?.  Aliment Pharmacol Ther. 2004;  19 1277-1283
• 7 Hischenhuber C, Crevel R, Jarry B. et al . Review article: safe amounts of gluten for patients with wheat allergy or coeliac disease.  Aliment Pharmacol Ther. 2006;  23 559-575
• 8 Case S. The gluten-free diet: How to provide effective education and resources.  Gastroenterology. 2005;  128 S128-S134
• 9 Stern M, Ciclitira P J, van Eckert R. et al . Analysis and clinical effects of gluten in coeliac disease.  Eur J Gastroenterol Hepatol. 2001;  13 741-747
• 10 Weinstein W M. Latent celiac sprue.  Gastroenterology. 1974;  66 489-493
• 11 Ciclitira P J, Ellis H J, Lundin K E. Gluten-free diet - what is toxic?.  Best Pract Res Clin Gastroenterol. 2005;  19 359-371
• 12 van de Wal Y, Kooy Y M, van Veelen P. et al . Glutenin is involved in the gluten-driven mucosal T cell response.  Eur J Immunol. 1999;  29 3133-3139
• 13 Vader W, Kooy Y, van Veelen P. et al . The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides.  Gastroenterology. 2002;  122 1729-1737
• 14 Molberg O, Solheim F N, Jensen T. et al . Intestinal T-cell responses to high-molecular-weight glutenins in celiac disease.  Gastroenterology. 2003;  125 337-344
• 15 Mothes T, Stern M. How gluten-free is gluten-free, and what does this mean to coeliac patients?.  Eur J Gastroenterol Hepatol. 2003;  15 461-463
• 16 Catassi C, Fabiani E, Mandolesi A. et al .The Italian study on gluten microchallenge: preliminary results. Stern M Proceedings of the 19th meeting; working group on prolamin analysis and toxicity Zwickau; Verlag wissenschaftliche Scripten 2005: 109-114
• 17 Valdes I, Garcia E, Llorente M. et al . Innovative approach to low-level gluten determination in foods using a novel sandwich enzyme-linked immunosorbent assay protocol.  Eur J Gastroenterol Hepatol. 2003;  15 465-474
• 18 Stern M. A major step towards a practical and meaningful gluten analysis.  Eur J Gastroenterol Hepatol. 2005;  17 523-524
• 19 Collin P, Maki M, Kaukinen K. It is the compliance, not milligrams of gluten, that is essential in the treatment of celiac disease.  Nutr Rev. 2004;  62 490
• 20 Kasarda D D, Okita T W, Bernardin J E. et al . Nucleic acid (cDNA) and amino acid sequences of a-type gliadins from wheat (Triticum aestivum L.).  Proc Natl Acad Sci USA. 1984;  81 4712
• 21 Hardman C M, Garioch J J, Leonard J N. et al . Absence of toxicity of oats in patients with dermatitis herpetiformis.  N Engl J Med. 1997;  337 1884-1887
• 22 Hogberg L, Laurin P, Falth-Magnusson K. et al . Oats to children with newly diagnosed coeliac disease: a randomised double blind study.  Gut. 2004;  53 649-654
• 23 Janatuinen E K, Kemppainen T A, Pikkarainen P H. et al . Lack of cellular and humoral immunological responses to oats in adults with coeliac disease.  Gut. 2000;  46 327-331
• 24 Janatuinen E K, Kemppainen T A, Julkunen R JK. et al . No harm from five year ingestion of oats in coeliac disease.  Gut. 2002;  50 332-335
• 25 Vader L W, de Ru A, WY. et al . Specificity of tissue transglutaminase explains cereal toxicity in celiac disease.  J Exp Med. 2002;  195 643-649
• 26 Kilmartin C, Lynch S, Abuzakouk M. et al . Avenin fails to induce a Th1 response in coeliac tissue following in vitro culture.  Gut. 2003;  52 47-52
• 27 Peraaho M, Kaukinen K, Mustalahti K. et al . Effect of an oats-containing gluten-free diet on symptoms and quality of life in coeliac disease. A randomized study.  Scand J Gastroenterol. 2004;  39 27-31
• 28 Lundin K E, Nilsen E M, Scott H G. et al . Oats induced villous atrophy in coeliac disease.  Gut. 2003;  52 1649-1652
• 29 Peraaho M, Collin P, Kaukinen K. et al . Oats can diversify a gluten-free diet in celiac disease and dermatitis herpetiformis.  J Am Diet Assoc. 2004;  104 1148-1150
• 30 Dickey W, Hughes D F. Histology of the terminal ileum in coeliac disease.  Scand J Gastroenterol. 2004;  39 665-667
• 31 Dickey W. Low serum vitamin B12 is common in coeliac disease and is not due to autoimmune gastritis.  Eur J Gastroenterol Hepatol. 2002;  14 425-427
• 32 Vahedi K, Mascart F, Mary J Y. et al . Reliability of antitransglutaminase antibodies as predictors of gluten-free diet compliance in adult celiac disease.  Am J Gastroenterol. 2003;  98 1079-1087
• 33 Walker-Smith J A, Guandalini S, Schmitz J. et al . Revised criteria for diagnosis of coeliac disease.  Arch Dis Child. 1990;  65 909-911
• 34 Hill I D, Dirks M H, Liptak G S. et al . Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.  J Pediatr Gastroenterol Nutr. 2005;  40 1-19
• 35 National Institutes of Health Consensus Development Conference Statement on Celiac Disease, 28 - 30.6.2004.  Gastroenterology. 2005;  128 S1-S9
• 36 Kaukinen K, Sulkanen S, Maki M. et al . IgA-class transglutaminase antibodies in evaluating the efficacy of gluten-free diet in coeliac disease.  Eur J Gastroenterol Hepatol. 2002;  14 311-315
• 37 Pietzak M M. Follow-up of patients with celiac disease: Achieving compliance with treatment.  Gastroenterology. 2005;  128 S135-S141
• 38 Bazzigaluppi E, Roggero P, Parma B. et al . Antibodies to recombinant human tissue-transglutaminase in coeliac disease: Diagnostic effectiveness and decline pattern after gluten-free diet.  Dig Liver Dis. 2006;  38 98-102
• 39 Fabiani E, Catassi C. The serum IgA class anti-tissue transglutaminase antibodies in the diagnosis and follow up of coeliac disease. Results of an international multi-centre study. International Working Group on Eu-tTG.  Eur J Gastroenterol Hepatol. 2001;  13 659-665
• 40 Wahab P J, Meijer J WR, Mulder C JJ. Histologic follow-up of people with celiac disease on a gluten- free diet - Slow and incomplete recovery.  Am J Clin Pathol. 2002;  118 459-463
• 41 Collin P, Maki M, Kaukinen K. Complete small intestine mucosal recovery is obtainable in the treatment of celiac disease.  Gastrointest Endosc. 2004;  59 158-159
• 42 Lee S K, Lo W, Memeo L. et al . Duodenal histology in patients with celiac disease after treatment with a gluten-free diet.  Gastrointes Endoscopy. 2003;  57 187-191
• 43 Tursi A, Brandimarte G, Giorgetti G M. Lack of usefulness of anti-transglutaminase antibodies in assessing histologic recovery after gluten-free diet in celiac disease.  J Clin Gastroenterol. 2003;  37 387-391
• 44 Schmitz J. Is celiac disease a lifelong disorder?.  Clin Invest Med. 1996;  19 352-356
• 45 Walker-Smith J. Transient gluten intolerance.  Arch Dis Child. 1970;  45 523-526
• 46 Meuli R, Pichler W J, Gaze H. et al . Genetic difference in HLA-DR phenotypes between coeliac disease and transitory gluten intolerance.  Arch Dis Child. 1995;  72 29-32
• 47 Limbach A, Hoepffner W, Tannapfel A. et al . Long-term study of patients with coeliac disease in childhood and adolescence: latent and transient coeliac disease.  Klin Padiatr. 2003;  215 76-81
• 48 Fasano A. European and North American populations should be screened for coeliac disease.  Gut. 2003;  52 168-169
• 49 Kumar P J. European and North American populations should be screened for coeliac disease.  Gut. 2003;  52 170-171
• 50 Lebwohl B, Green P H. Screening for celiac disease.  N Engl J Med. 2003;  349 1673-1674
• 51 Collin P. Should adults be screened for celiac disease? What are the benefits and harms of screening?.  Gastroenterology. 2005;  128 S104-S108
• 52 Holmes G K, Prior P, Lane M R. et al . Malignancy in coeliac disease - effect of a gluten free diet.  Gut. 1989;  30 333-338
• 53 Mearin M L, Catassi C, Brousse N. et al . European multi-centre study on coeliac disease and non-Hodgkin lymphoma.  Eur J Gastroenterol Hepatol. 2006;  18 187-194
• 54 Ventura A, Magazzu G, Greco L. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease.  Gastroenterology. 1999;  117 297-303
• 55 Sategna G C, Solerio E, Scaglione N. et al . Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders.  Gut. 2001;  49 502-505
• 56 Viljamaa M, Kaukinen K, Huhtala H. et al . Coeliac disease, autoimmune diseases and gluten exposure.  Scand J Gastroenterol. 2005;  40 437-443
• 57 Mustalahti K, Lohiniemi S, Collin P. et al . Gluten-free diet and quality of life in patients with screen-detected celiac disease.  Eff Clin Pract. 2002;  5 105-113
• 58 Johnston S D, Rodgers C, Watson R G. Quality of life in screen-detected and typical coeliac disease and the effect of excluding dietary gluten.  Eur J Gastroenterol Hepatol. 2004;  16 1281-1286
• 59 Fabiani E, Taccari L M, Ratsch I M. et al . Compliance with gluten-free diet in adolescents with screening-detected celiac disease: a 5-year follow-up study.  J Pediatr. 2000;  136 841-843
• 60 Mayer M, Greco L, Troncone R. et al . Compliance of adolescents with coeliac disease with a gluten free diet.  Gut. 1991;  32 881-885
• 61 Kumar P J, Walker-Smith J, Milla P. et al . The teenage coeliac: follow up study of 102 patients.  Arch Dis Child. 1988;  63 916-920
• 62 Bardella M T, Molteni N, Prampolini L. et al . Need for follow up in coeliac disease.  Arch Dis Child. 1994;  70 211-213
• 63 Corrao G, Corazza G R, Bagnardi V. et al . Mortality in patients with coeliac disease and their relatives: a cohort study.  Lancet. 2001;  358 356-361
• 64 Peters U, Askling J, Gridley G. et al . Causes of death in patients with celiac disease in a population-based Swedish cohort.  Arch Intern Med. 2003;  163 1566-1572
• 65 Kemppainen T, Kroger H, Janatuinen E. et al . Osteoporosis in adult patients with celiac disease.  Bone. 1999;  24 249-255
• 66 Corazza G R, Di Sario A, Cecchetti L. et al . Bone mass and metabolism in patients with celiac disease.  Gastroenterology. 1995;  109 122-128
• 67 Corazza G R, Di Sario A, Cecchetti L. et al . Influence of pattern of clinical presentation and of gluten-free diet on bone mass and metabolism in adult coeliac disease.  Bone. 1996;  18 525-530
• 68 Thomason K, West J, Logan R F. et al . Fracture experience of patients with coeliac disease: a population based survey.  Gut. 2003;  52 518-522
• 69 West J, Logan R F, Card T R. et al . Fracture risk in people with celiac disease: a population-based cohort study.  Gastroenterology. 2003;  125 429-436
• 70 Bernstein C N, Leslie W D, Leboff M S. AGA technical review on osteoporosis in gastrointestinal diseases.  Gastroenterology. 2003;  124 795-841
• 71 Collin P, Vilska S, Heinonen P K. et al . Infertility and coeliac disease.  Gut. 1996;  39 382-384
• 72 Sher K S, Jayanthi V, Probert C S. et al . Infertility, obstetric and gynaecological problems in coeliac sprue.  Dig Dis. 1994;  12 186-190
• 73 Sher K S, Mayberry J F. Female fertility, obstetric and gynaecological history in coeliac disease. A case control study.  Digestion. 1994;  55 243-246
• 74 Tata L J, Card T R, Logan R F. et al . Fertility and pregnancy-related events in women with celiac disease: a population-based cohort study.  Gastroenterology. 2005;  128 849-855
• 75 Farthing M J, Rees L H, Edwards C R. et al . Male gonadal function in coeliac disease: 2. Sex hormones.  Gut. 1983;  24 127-135
• 76 Farthing M J, Rees L H, Dawson A M. Male gonadal function in coeliac disease: III. Pituitary regulation.  Clin Endocrinol (Oxf). 1983;  19 661-671
• 77 Hozyasz K K. Coeliac disease and birth defects in offspring.  Gut. 2001;  49 738
• 78 Ludvigsson J F, Montgomery S M, Ekbom A. Celiac disease and risk of adverse fetal outcome: a population-based cohort study.  Gastroenterology. 2005;  129 454-463
• 79 Sheiner E, Peleg R, Levy A. Pregnancy outcome of patients with known celiac disease.  Eur J Obstet Gynecol Reprod Biol. 2005; ;  , article ahead of print: http://dx.doi.org/10.1016/j.ejogrb.2005.10.023
• 80 Ryan B M, Kelleher D. Refractory celiac disease.  Gastroenterology. 2000;  119 243-251
• 81 Trier J S, Falchuk Z M, Carey M C. et al . Celiac sprue and refractory sprue.  Gastroenterology. 1978;  75 307
• 82 Cellier C, Delabesse E, Helmer C. et al . Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma.  Lancet. 2000;  356 203-208
• 83 Catassi C, Bearzi I, Holmes G KT. Association of celiac disease and intestinal lymphomas and other cancers.  Gastroenterology. 2005;  128 S79-S86
• 84 Biagi F, Corazza G R. Defining gluten refractory enteropathy.  Eur J Gastroenterol Hepatol. 2001;  13 561-565
• 85 Verkarre V, Asnafi V, Lecomte T. et al . Refractory coeliac sprue is a diffuse gastrointestinal disease.  Gut. 2003;  52 205-211
• 86 Daum S, Cellier C, Mulder C J. Refractory coeliac disease.  Best Pract Res Clin Gastroenterol. 2005;  19 413-424
• 87 Goldstein N S. Non-gluten sensitivity-related small bowel villous flattening with increased intraepithelial lymphocytes: not all that flattens is celiac sprue.  Am J Clin Pathol. 2004;  121 546-550
• 88 Goerres M S, Meijer J W, Wahab P J. et al . Azathioprine and prednisone combination therapy in refractory coeliac disease.  Aliment Pharmacol Ther. 2003;  18 487-494
• 89 Corazza G R, Biagi F, Volta U. et al . Autoimmune enteropathy and villous atrophy in adults.  Lancet. 1997;  350 106-109
• 90 Rolny P, Sigurjonsdottir H A, Remotti H. et al . Role of immunosuppressive therapy in refractory sprue-like disease.  Am J Gastroenterol. 1999;  94 219-225
• 91 Turner S M, Moorghen M, Probert C S. Refractory coeliac disease: remission with infliximab and immunomodulators.  Eur J Gastroenterol Hepatol. 2005;  17 667-669
• 92 Daum S, Ipczynski R, Heine B. et al . Therapy with budesonide in patients with refractory sprue.  Digestion. 2006;  73 60-68
• 93 Vaidya A, Bolanos J, Berkelhammer C. Azathioprine in refractory sprue.  Am J Gastroenterol. 1999;  94 1967-1969
• 94 Olaussen R W, Lovik A, Tollefsen S. et al . Effect of elemental diet on mucosal immunopathology and clinical symptoms in type 1 refractory celiac disease.  Clin Gastroenterol Hepatol. 2005;  3 875-885
• 95 Daum S, Weiss D, Hummel M. et al . Frequency of clonal intraepithelial T lymphocyte proliferations in enteropathy-type intestinal T cell lymphoma, coeliac disease, and refractory sprue.  Gut. 2001;  49 804-812
• 96 Daum S, Hummel M, Weiss D. et al . Refractory sprue syndrome with clonal intraepithelial lymphocytes evolving into overt enteropathy-type intestinal T- cell lymphoma.  Digestion. 2000;  62 60-65
• 97 Cellier C, Patey N, Mauvieux L. et al . Abnormal intestinal intraepithelial lymphocytes in refractory sprue.  Gastroenterology. 1998;  114 471-481
• 98 Holtmeier W, Witthöft T, Hennemann A. et al . The TCR-α repertoire in human intestine undergoes characteristic changes during fetal to adult development.  J Immunol. 1997;  158 5632-5641
• 99 Holtmeier W. Compartmentalization of γ/δ T cells and their putative role in mucosal immunity.  Crit Rev Immunol. 2003;  23 473-488
• 100 Balk S P, Ebert E C, Blumenthal R L. et al . Oligoclonal expansion and CD1 recognition by human intestinal intraepithelial lymphocytes.  Science. 1991;  253 1411-1415
• 101 Gross G G, Schwartz V L, Stevens C. et al . Distribution of dominant T cell receptor β chains in human intestinal mucosa.  J Exp Med. 1994;  180 1337-1344
• 102 Weinstein W M, Saunders D R, Tytgat G N. et al . Collagenous sprue - An unrecognized type of malabsorption.  N Engl J Med. 1970;  283 1297
• 103 Medlicott S A, Beck P L, Loken S. et al . Synchronous collagenous sprue and enteropathy-type T cell lymphoma: variants of the same disease.  Can J Gastroenterol. 2004;  18 329-332
• 104 Freeman H J. Collagenous sprue associated with an extensive T-cell lymphoma.  J Clin Gastroenterol. 2003;  36 144-146
• 105 Freeman H J. Collagenous mucosal inflammatory diseases of the gastrointestinal tract.  Gastroenterology. 2005;  129 338-350
• 106 Bossart R, Henry K, Booth C C. et al . Subepithelial collagen in intestinal malabsorption.  Gut. 1975;  16 18
• 107 Olesen M, Eriksson S, Bohr J. et al . Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients.  Gut. 2004;  53 536-541
• 108 Chande N, McDonald J, Macdonald J. et al . Interventions for treating collagenous colitis.  Cochrane Database Syst Rev. 2005;  CD003575
• 109 Bonderup O K, Hansen J B, Birket-Smith L. et al . Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis.  Gut. 2003;  52 248-251
• 110 Biagi F, Lorenzini P, Corazza G R. Literature review on the clinical relationship between ulcerative jejunoileitis, coeliac disease, and enteropathy-associated T-cell.  Scand J Gastroenterol. 2000;  35 785-790
• 111 Elsing C, Placke J, Gross-Weege W. Ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma.  Eur J Gastroenterol Hepatol. 2005;  17 1401-1405
• 112 Swinson C M, Slavin G, Coles E C. et al . Coeliac disease and malignancy.  Lancet. 1983;  1 111-115
• 113 Cooper B T, Holmes G K, Cooke W T. Lymphoma risk in coeliac disease of later life.  Digestion. 1982;  23 89-92
• 114 Card T R, West J, Holmes G K. Risk of malignancy in diagnosed coeliac disease: a 24-year prospective, population-based, cohort study.  Aliment Pharmacol Ther. 2004;  20 769-775
• 115 Catassi C, Fabiani E, Corrao G. et al . Risk of non-Hodgkin lymphoma in celiac disease.  JAMA. 2002;  287 1413-1419
• 116 Askling J, Linet M, Gridley G. et al . Cancer incidence in a population-based cohort of individuals hospitalized with Celiac disease or dermatitis herpetiformis.  Gastroenterology. 2002;  123 1428-1435
• 117 Loftus C G, Loftus E V, Jr. Cancer risk in celiac disease.  Gastroenterology. 2002;  123 1726-1729
• 118 Smedby K E, Akerman M, Hildebrand H. et al . Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma.  Gut. 2005;  54 54-59
• 119 Hervonen K, Vornanen M, Kautiainen H. et al . Lymphoma in patients with dermatitis herpetiformis and their first-degree relatives.  Br J Dermatol. 2005;  152 82-86
• 120 Holmes G KT. Coeliac disease and malignancy.  Digestive and Liver Disease. 2002;  34 229-237
• 121 Howdle P D, Holmes G KT. Small bowel malignancy in coeliac disease.  Gut. 2004;  53 470
• 122 Howdle P D, Jalal P K, Holmes G KT. et al . Primary small-bowel malignancy in the UK and its association with coeliac disease.  Qjm-An International Journal of Medicine. 2003;  96 345-353
• 123 Alberg A J, Samet J M. Epidemiology of lung cancer.  Chest. 2003;  123 21S-49S
• 124 Hausch F, Halttunen T, Maki M. et al . Design, synthesis, and evaluation of gluten Peptide analogs as selective inhibitors of human tissue transglutaminase.  Chem Biol. 2003;  10 225-231
• 125 Sollid L M, Khosla C. Future therapeutic options for celiac disease.  Nat Clin Pract Gastroenterol Hepatol. 2005;  2 140-147
• 126 Shan L, Molberg O, Parrot I. et al . Structural basis for gluten intolerance in celiac sprue.  Science. 2002;  297 2275-2279
• 127 Cornell H J, Macrae F A, Melny J. et al . Enzyme therapy for management of coeliac disease.  Scand J Gastroenterol. 2005;  40 1304-1312
• 128 Holtmeier W, Caspary W F. Identification of toxic gliadin fragments - new therapeutic options for patients suffering from coeliac disease (nontropical sprue)?.  Z Gastroenterol. 2002;  40 999-1000
• 129 Matysiak-Budnik T, Candalh C, Cellier C. et al . Limited efficiency of prolyl-endopeptidase in the detoxification of gliadin peptides in celiac disease.  Gastroenterology. 2005;  129 786-796
• 130 Molberg O, Uhlen A K, Jensen T. et al . Mapping of gluten T-cell epitopes in the bread wheat ancestors: Implications for celiac disease.  Gastroenterology. 2005;  128 393-401
• 131 Spaenij-Dekking L, Kooy-Winkelaar Y, van Veelen P. et al . Natural variation in toxicity of wheat: potential for selection of nontoxic varieties for celiac disease patients.  Gastroenterology. 2005;  129 797-806
• 132 Spaenij-Dekking L, Kooy-Winkelaar Y, Koning F. The Ethiopian cereal tef in celiac disease.  N Engl J Med. 2005;  353 1748-1749