International Journal of Celiac Disease
ISSN (Print): 2334-3427 ISSN (Online): 2334-3486 Website: http://www.sciepub.com/journal/ijcd Editor-in-chief: Samasca Gabriel
Open Access
Journal Browser
Go
International Journal of Celiac Disease. 2021, 9(1), 28-34
DOI: 10.12691/ijcd-9-1-1
Open AccessArticle

Enzyme Therapy for Patients with Celiac Disease - An Update

Hugh J. Cornell1, Teodor Stelmasiak2, and Aaron Lerner3

1RMIT University, School at Applied Science, Melbourne, Australia

2Glutagen Pty Ltd, Melbourne, Australia

3Chaim Sheba Medical Center, The Zabludowicz Research Center for Autoimmune Diseases, Tel Hashomer, Israel

Pub. Date: January 21, 2021

Cite this paper:
Hugh J. Cornell, Teodor Stelmasiak and Aaron Lerner. Enzyme Therapy for Patients with Celiac Disease - An Update. International Journal of Celiac Disease. 2021; 9(1):28-34. doi: 10.12691/ijcd-9-1-1

Abstract

Enzyme therapy as a management tool for patients with celiac disease (CD) or gluten intolerance is gaining acceptance around the world. Gluten has multiple side effects and limitations of a gluten-free diet (GFD) in management of CD are evident and mainly related to the presence of hidden gluten or cross-contamination of meals in restaurants. The present paper discusses enzyme therapy with caricain, namely Gluteguard, in light of various approaches searching for a treatment or an effective management of CD. Regular users of the supplement Gluteguard report a high level of satisfaction with the product. This indicates that enzyme therapy based on caricain has its place as a safeguard when the gluten-free meals are prepared outside the control of the patients.

Keywords:
celiac disease enzyme therapy caricain gluten-free diet gluten intolerance dermatitis herpetiformis

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]  Mäki M. Collin P. Coeliac Disease. Lancet. 1997; 349: 1755-1759.
 
[2]  Lerner A. Matthias T. Autoimmunity in celiac disease: extra- intestinal manifestations. Autoimm. Rev. 2019; 18:241-246.
 
[3]  Ilus T. Kaukinen K. Virta L J. Pukkala E. Collin P. Incidence of malignancies in diagnosed celiac patients: a population-based estimate. Am J Gastroenterol. 2014; 109: 1471-1477.
 
[4]  Lerner A. Makhoul BF. Eliakim R. Neurological manifestations of celiac disease in children and adults. Europ Neurolog J. 2012; 4: 15-20.
 
[5]  Lerner A. Shoenfeld Y. Matthias T. A Review: Gluten ingestion side effects and withdrawal advantages in non-celiac autoimmune diseases. Nutritional Rev. 2017; 75: 1046-1058.
 
[6]  Lerner A. Matthias T. Gluten free diet- tough ally in torrid time. Internat J of Celiac Dis. 2017; 5: 50-55.
 
[7]  Lerner A. New Therapeutic Strategies for Celiac Disease. Autoimmun. Rev. 2010; 9: 144-147.
 
[8]  Shaoul R. Lerner A. Associated autoantibodies in celiac disease. Autoimmun. Rev. 2007; 6: 559-565.
 
[9]  Fasano A. Zonulin and its regulation of intestinal barrier. 2011; 91(1): 151-75.
 
[10]  Krishnareddy S. The Microbiome in Celiac Disease. Gastroenterol Clin North Amer. 2019; 48: 115-126.
 
[11]  Croese J. Giacomin P. Navarro S. Clouston A. McCann L. Dougall A. Ferreira I. Susianto A. O'Rourke P. Howlett M. McCarthy J. Engwerda C. Jones D. Loukas A. Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J Allergy ClinImmunol.2015; 135: 508-516.
 
[12]  Goel, G., King T., Daveson, A.J. et al. Epitope specific immunotherapy targeting CD4positive T cells in coeliac disease: two randomized, double-blind, placebo controlled phase 1 studies. Lancet Gastroenterol Hepatol. 2017; 2: 479-493.
 
[13]  Alhassan E. Yadav A. Kelly C.P. Rupa M. Novel non-dietary therapies for celiac disease. CMG&H. 2019; 8: 335-345.
 
[14]  Sollid LM. The roles of MHC class II genes and post-translational modification in celiac disease. Immunogenetics. 2017; 69: 605-616.
 
[15]  Frazer AC. Fletcher RF. Ross CAC. Shaw B. Sammons H. Schneider R. Gluten induced enteropathy: The effect partially digested gluten. Lancet.1959; 274: 252-255.
 
[16]  Cornell, H.J. Townley, R.R. The toxicity of certain cereal proteins in coeliac disease. Gut.1974; 15: 862-869.
 
[17]  Cornell H.J. and Rivett D.E. In vitro’ mucosal digestion of synthetic gliadin-derived peptides in coeliac disease. J.Protein Chem. 1995; 14: 335-339.
 
[18]  Falchuk ZM. Strober W. Gluten sensitive enteropathy: synthesis of antigliadin antibody in vitro. Gut.1974; 15: 947-952.
 
[19]  Schuppan D. Hahn, EG. Gluten and the gut - lessons for immune regulation. Science.2002; 297: 2218-2220.
 
[20]  Bethune MT. Ribka E. Khosla C. Sestak K. Transepithelial transport and enzymatic detoxification of gluten in gluten-sensitive rhesus macaques. PLOS ONE. 2008; 3(3): e1857.
 
[21]  Kelly CP. Green PH. Murray JA. Dimarino A. Colatrella A. Leffler DA. Alexander T. Arsenescu R. Leon F. Jiang JG. Arterburn LA. Paterson BM. Fedorak RN.Larazotide Acetate Celiac Disease Study Group. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomized placebo-controlled study. Aliment Pharmacol Ther. 2013; 37(2): 252-62.
 
[22]  Hausch F. Shan L. Santiago NA. Gray GM. Khosla C. Intestinal digestive resistance of immunodominant gliadin peptides. Am J Physiol Gastrointest Liver Physiol. 2002; 283: G996-G1003
 
[23]  Cornell H.J. Stelmasiak T. Enzyme Supplementation in Coeliac Disease.The 11th International Symposium on Coeliac Disease, April 2004, Belfast, Northern Ireland.
 
[24]  Mothes T. Muhle W. Muller F. Hekkens WTJM. Influence of gliadin on foetal chick intestine in tissue culture. Biol. Neonate. 1985; 48: 59-64.
 
[25]  Cornell HJ. Auricchio RS. De Ritis G. Vincenzi M. Maiuri L. Raia V. Silano V. Intestinal mucosa of coeliacs in remission is unable to abolish toxicity of gliadin peptides on in vitro developing fetal rat intestine and cultured atrophic coeliac mucosa. Paediatric Research. 1998; 24: 233-237.
 
[26]  Sciurti M. Fornaroli F. Gaiani F. et al. Genetic susceptibility and celiac disease: what role do HLA haplotypes play? Acta Biomed. 2018; 89(9-S): 17-21.
 
[27]  Husby S. Koletzko S. Korponay-Szabó IR. Mearin ML. Phillips A. Shamir R. Troncone R. Giersiepen K. Branski D. Catassi C. Lelgeman M. Mäki M. Ribes-Koninckx . Ventura A. Zimmer KP. European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012; 54: 136-160.
 
[28]  Lerner A. Matthias T. Gluten and autoimmunogenesis. In Mosaic of Autoimmunity, The novel factors of autoimmune diseases revisited. 2nd edition, Eds: Shoenfield Y, Perricone C. Pub: Elsevier. 2019. pp: 315-321.
 
[29]  Dolly JO. Fottrell PF. Effect of different peptide fractions from wheat gliadin on rat liver lysosomes. Irish J. Med. Sc. 1969; 2: 47.
 
[30]  Riecken, E. O. Stewart, J. S. Booth, C. C. Pearse, A. G. E. A histochemical study on the role of lysosomal enzymes in idiopathic steatorrhoea before and during a gluten-free diet.Gut.1966; 7: 317-332.
 
[31]  Jabri B. Kasarda DD. Green PH. Innate and adaptive immunity: the yin and yang of celiac disease. Immunol Rev. 2005; 206: 219-31.
 
[32]  Cornell HJ. Stelmasiak T. A unified hypothesis of coeliac disease with implications for management of patients. Amino Acids.2007; 33:43-49.
 
[33]  Cornell HJ. Wills-Johnson G. Structure activity relationships in coeliac-toxic gliadin peptides. Amino Acids.2001; 21: 243-253.
 
[34]  Truitt KE. Ee HC. Goel G. MacDougall J. Neff K. Anderson RP. Randomized clinical trial: a randomized, placebo controlled clinical trial of subcutaneous or intradermal Nexvax2, an investigational immunomodulatory peptide therapy for coeliac disease. Aliment Pharmacol Ther. 2019; 50:547-555.
 
[35]  Cornell HJ. and Rolles CJ. Further evidence of a primary mucosal defect in coeliac disease.Gut.1978; 19: 253-259.
 
[36]  Bonamico M, Ferri M, Mariani P, Nenna R, Thanasi E, Luparia RP, Picarelli A, Magliocca FM, Mora B, Bardella MT, Verrienti A, Fiore B, Uccini S, Megiorni F, Mazzilli MC, Tiberti C. Serologic and genetic markers of celiac disease: a sequential study in the screening of first degree relatives. J Pediatr Gastroenterol Nutr. 2006; 42(2):150-4.
 
[37]  Dolinsek J. Urlep D. Karell K. Partanen J. Micetić-Turk D. The prevalence of celiac disease among family members of celiac disease patients.Wien KlinWochenschr. 2004; 116 Suppl 2:8-12.
 
[38]  Uhde M. Ajamian M. Caio G. De Giorgio R. Indart A. Green P. Verna E C. Volta U. Alaedini, A. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease Gut. 2016; 65: 1930-1937.
 
[39]  Silvester J A. Graff L A. Rigaux L. Walker JR. Duerksen DR. Symptomatic suspected gluten exposure is common among patients with coeliac disease on a gluten-free diet. Aliment Pharmacol Ther. 2016; 44: 612-619.
 
[40]  Halmos EP. Di Bella CA.Webster R. Deng M. Tye-Din JA. Gluten in “gluten-free” food from food outlets in Melbourne: a cross-sectional study. 2018; Med J Aust. Published online: 28 May 2018.
 
[41]  Macrae FA. Enzyme therapy that can digest the toxic motifs of gluten as an aid in the management of celiac disease. International Journal of Celiac Disease. 2018; 6(1), 4-6.
 
[42]  White L.E. Bannerman E. Gillett P.M. Coeliac disease and the gluten-free diet: A review of the burdens; factors associated with adherence and impact on health-related quality of life, with specific focus on adolescence. J. Hum. Nutr.Diet.2016; 29: 593-606.
 
[43]  Abdulkarim AS. Burgart LJ. SeeJ. Murray JA. Etiology of nonresponsive celiac disease: results of a systematic approach. Am.J.Gastroenterol. 2002; 97: 2016-2021.
 
[44]  Schuppan D. JunkerY. BarisaniD. Celiac disease: from pathogenesis to novel therapies. Gastroenterol. 2009; 137(6): 1912-33.
 
[45]  Schuppan D. Gisbert-Schuppan K. Wheat Syndromes: How Wheat, Gluten and ATI Cause Inflammation, IBS and Autoimmune Diseases. Springer; Cham, Switzerland: 2019.
 
[46]  Ludvigsson JF. Montgomery SM. Ekbom A. et al. Small-intestinal histopathology and mortality risk in celiac disease. JAMA.2009; 302: 1171-8.
 
[47]  Catassi C. Fabiani E. Iacono G. D’Agate C. Francavilla R. Biagi F. Volta U. Accomando S. Picarelli A. De Vitis I. et al. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am. J. Clin. Nutr.2007; 85: 160-166.
 
[48]  Biagi F. Campanella J. Martucci S. Pezzimenti D. Ciclitira PJ. Ellis HJ.Corazza, GR. A milligram of gluten a day keeps the mucosal recovery away: A case report. Nutrition Reviews. 2004; 62: 360-363.
 
[49]  Rostami K. Bold J. Parr A. Johnson MW. Gluten-free diet indications, safety, quality, labels, and challenges. Nutrients. 2017 Aug 8; 9(8): 846.
 
[50]  Halmos E. How gluten free is gluten-free diet. The Australian Coeliac.2016; December Issue. p.11-12.
 
[51]  Lerner A, O’Bryan T, Matthias T. Navigating the gluten-free diet boom: the dark side of gluten free diet. Front Pediatr. 2019; 7: Article 414.
 
[52]  Cornell H.J. Macrae F.A. Melny J. Pizzey C.J. Cook F. Mason S. Bhathal P.S. Stelmasiak T. (2005). Enzyme therapy for management of coeliac disease. Scand. J.Gastroenterology 40: 1304-1312.
 
[53]  Cornell H.J. Czyzewska A. Macrae F.A. Rydzewska G. Nasierowska-Gutmejer A. Bednarczuk A. Stelmasiak T. The effect of enzyme supplementation on symptoms and duodenal histology in celiac patients. International Journal of Celiac Disease.2016; 4: 40-47.
 
[54]  Lerner BA. Phan Vo LT. Yates S. Rundle AG. Green PHR. Lebwohl B. Detection of gluten in gluten-free labeled restaurant food: analysis of crowd-sourced data. Am J Gastroenterol. 2019; 114: 792-797.
 
[55]  De Ritis G. Auricchio S. Jones H W. Lew E J L. Bernardin J E & Kasarda D. In vitro (organ culture) studies of the toxicity of specific A-gliadin peptides in coeliac disease. Gastroenterology. 1988; 94: 41-49.
 
[56]  Cornell HJ. Doherty W. Stelmasiak T. Papaya latex enzymes capable of detoxification of gliadin. Amino Acids.2010; 38: 155-165.
 
[57]  Cornell H J. & Stelmasiak T. Caricain: A basis for enzyme therapy for coeliac disease. South African Journal of Science. 2011; 107: 74-78.
 
[58]  Cornell HJ. Stelmasiak T. The significance of key amino acid sequences in the digestibility and toxicity of gliadin peptides in celiac disease. International Journal of Celiac Disease.2016; 4: 113-120.
 
[59]  Zebrowska A. Cornell HJ. Macrae FA. Sysa-Jedrzejowska A. Waszczykowska A. Stelmasiak, T. The effect of enzyme therapy on skin symptoms and immune responses in patients with dermatitis herpetiformis. International Journal of Celiac Disease. 2014; 2: 58-63.
 
[60]  Lerner A. Is Enzyme Supplementation Effective Strategy to Reduce the Burden of Gluten Free Diet in Celiac Disease? International Journal of Celiac Disease.2016; 4: 38-39.
 
[61]  Tanner G. Juhász A. Florides CG. Relative rates of gluten digestion by nine commercial dietary digestive supplements. 2019; Poster presentation. Digestive Diseases Week, San Diego, USA.
 
[62]  Lerner A. Makhoul B. F. and Eliakim R. Neurological manifestations of celiac disease in children and adults. European Neurological Journal. 2012; 4. 15-20..
 
[63]  Arnone JM. Conti RP. Neuropsychiatric features of celiac disease. International Journal of Celiac Disease. 2015; 3: 77-83.
 
[64]  Pennisi M. Bramanti A. Cantone M. Pennisi G. Bella R. Lanza G. Neurophysiology of the "Celiac Brain": Disentangling Gut-Brain Connections. Front Neurosci. 2017; 11: 498.
 
[65]  Campagna G. Pesce M. Tatangelo R. Rizzuto A. La Fratta I. Grilli A. The progression of coeliac disease: its neurological and psychiatric implications. Nutr. Res. Rev. 2017; 30: 25-35.
 
[66]  Lerner A. Matthias T. Going gluten free in non-celiac autoimmune diseases: The missing ingredient. Expert Rev Clin Immunol. 2018; 14: 873-875.
 
[67]  Lerner A, Ramesh A, Matthias T. Are Non-Celiac Autoimmune Diseases Responsive to Gluten-Free Diet? International Journal of Celiac Disease. 2017; 5:164-167.
 
[68]  Lerner A, Matthias T. The Yin and Yang of dietary gluten transgressions in real-life scenarios of celiac patients. BMC Medicine. 2020; 18:70-72.
 
[69]  Murray J.A. Kelly C.P. Green P.H.R. Marcantonio A. Wu T.T. Mäki M. Adelman D.C. No difference between latiglutenase and placebo in reducing villous atrophy or improving symptoms in patients with symptomatic celiac disease. Gastroenterology. 2017; 152: 787-798.
 
[70]  Tack G. J. et al. Consumption of gluten with gluten-degrading enzyme by celiac patients: a pilot-study. World J. Gastroenterol. 2013; 19: 5837-5847.
 
[71]  Theme 2020 Glutagen Facebook Survey (www.glutagen.com.au).