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.

• Klíčová slova
• caricain,
• MeSH
• bezlepková dieta MeSH
• celiakie farmakoterapie   metabolismus   MeSH
• cysteinové endopeptidasy MeSH
• dermatitis herpetiformis komplikace   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH

Several strategies have been considered for enzymatic detoxification of dietary gluten and to reduce immunogenisity of gliadin peptides. An enzymatic therapy using enterically coated tablets containing caricain (Gluteguard), originated from a papaya, on celiac disease patients challenged with gluten was reported. Glut guard was able to protect these patients from adverse symptoms being induced by gluten challenge. The advantages of the fruit originated preparation are: it does not contain living microbes or bacterial purified or engineered products. It can be considered as a preventive therapy and further step in the future therapeutical strategy race for the celiac affected population benefits.

• Klíčová slova
• caricain,
• MeSH
• bezlepková dieta MeSH
• celiakie * dietoterapie   imunologie   terapie   MeSH
• cysteinové endopeptidasy terapeutické užití   MeSH
• enzymová substituční terapie * MeSH
• lidé MeSH
• manipulace s potravinami MeSH
• rostlinné proteiny terapeutické užití   MeSH
• transglutaminasy metabolismus   MeSH
• vystavení vlivu životního prostředí MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• úvodní články MeSH

The importance of alternative or adjunct treatments to the gluten-free diet in celiac disease is now being recognized. This paper discusses the scientific principles behind the use of caricain for enzyme therapy. Objective: To review the structures of the toxic peptides in A-gliadin that relate to those found by other workers insofar as having key sequences of amino acids or motifs which relate to toxicity, especially in regard to difficulty of digestion or immunogenicity. Methods: Structures of synthetic A-gliadin peptides shown to be toxic in the fetal chick assay were examined before and after digestion with duodenal mucosa from patients in long remission. Synthetic peptides corresponding to the undigested residues were also assayed and the key amino acid sequences compared in order to determine if they could be related to direct toxicity and immunogenicity of the peptides. Results: The results showed that the smallest toxic peptides from celiac mucosal digestion were octa-peptides and that they were obtained in greater yield than similar products from normal digestion. One of those peptides corresponded to residues 12-19 of A-gliadin and contained the key motifs PSQQ and QQQP of De Ritis et al. , whilst the other corresponded to residues 72-79 and contained the key motif PYPQ (extending to PYPQPQ), observed by other workers, especially those who have been investigating immunological activity over the past two decades. Conclusions: The presence of key motifs in undigested residues from celiac mucosal digestion and the greater prevalence of these residues compared with residues from normal digestion justifies our work on enzyme therapy. These studies have also indicated that our use of caricain as an enzyme capable of digesting peptides with two different types of toxicity has a sound scientific basis.

• Klíčová slova
• caricain,
• MeSH
• celiakie * enzymologie   terapie   MeSH
• cysteinové endopeptidasy farmakologie   terapeutické užití   MeSH
• enzymoterapie * MeSH
• gliadin * chemie   metabolismus   toxicita   MeSH
• gluteny toxicita   účinky léků   MeSH
• lidé MeSH
• proteolýza MeSH
• rostlinné proteiny farmakologie   terapeutické užití   MeSH
• sekvence aminokyselin MeSH
• sekvenční analýza proteinů MeSH
• střevní sliznice patologie   MeSH
• tenké střevo patologie   MeSH
• tyrosin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Background: The etiology of celiac disease (CD) is related to undigested fragments of gluten and gliadin which damage the small bowel. Mucosal enzyme deficiency is an important factor in CD pathology. A clinical trial has shown that the effects of a gluten challenge to patients with CD could be ameliorated by the use of an enzyme supplement. Objective: Enzyme therapy using enterically coated tablets containing caricain (Gluteguard) was investigated as a means of protecting patients with CD against wheat gluten. Methods: A randomized placebo-controlled trial was carried out on 20 CD patients in clinical remission. The patients were divided into a group of 14 given Gluteguard and a group of 6 given a placebo daily. Both groups were given a challenge of 1g of gluten daily. Symptoms were graded and recorded over a period of 42 days. Duodenal tissue was taken at the beginning and end of this period, together with blood for assay of tissue transglutaminase (tTG-IgA) antibodies. Results: The results showed that oral enzyme therapy based on caricain, was effective in ameliorating the symptoms of CD giving a statistically significant difference between treatment and placebo (P<0.01) after 14 days challenge. General well-being was also improved from 6.1 to 8.4 (P< 0.01) by the enzyme therapy. Four of the six placebo group patients (67%) and one of the 14 treatment patients (7%) to withdraw from gluten challenge after 14 days due to development of serious symptoms. The difference between the groups was significant (p < 0.001). For the per protocol patients on Gluteguard therapy, there were no significant changes in markers of histological damage or biopsy results after 42 days of gluten challenge. Conclusions: This study demonstrated that oral anti-gluten enzyme therapy using Gluteguard was able to significantly protect celiac patients from adverse symptoms being induced by gluten challenge. Furthermore, mucosal damage was not exacerbated in patients taking Gluteguard along with their daily gluten challenge, suggesting that the enzyme tablets may also help with the recovery of epithelium in the longer term. Availability of a preventative enzyme treatment like Gluteguard will likely add to the quality of life and well-being of coeliac patients, especially those who have difficulty in strictly adhering to a gluten-free diet.

• Klíčová slova
• caricain, Gluteguard,
• MeSH
• celiakie * farmakoterapie   patologie   patofyziologie   MeSH
• cysteinové endopeptidasy terapeutické užití   MeSH
• dospělí MeSH
• duodenum patologie   MeSH
• enzymová substituční terapie * MeSH
• gluteny aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• protilátky krev   MeSH
• rostlinné proteiny terapeutické užití   MeSH
• senioři MeSH
• spokojenost pacientů MeSH
• statistika jako téma MeSH
• transglutaminasy metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• randomizované kontrolované studie MeSH

The aetiology of coeliac disease (CD) has many similarities to that of dermatitis herpetiformis (DH), except that DH lesions are mainly manifested in the skin. Mucosal enzyme deficiency plays an important part in CD pathology. Clinical studies indicated that the gluten exposure in CD could be partly corrected by the use of enzyme supplementation. Objective: Enzyme therapy, using enterically coated tablets containing caricain, was investigated as a means of protecting patients with DH against wheat gluten. Methods: A randomized, placebo-controlled clinical trial was carried out on 20 DH patients in clinical remission. The patients were divided into two groups of 10, one group given a placebo daily and the other the enzyme – containing tablets. Both groups were challenged with 6g of gluten daily in a double-blind trial. Symptoms and signs of skin involvement were recorded and graded at the start of the trial, after 7 days and after 14 days. Blood was also taken at the start and after 14 days and assayed for IgA EMA and anti-gliadin antibodies. Results: After 7 days the major features associated with DH were more severe and more common with the placebo compared with enzyme therapy. Before 14 days, seven patients in total, six on placebo, had to withdraw from the trial because of the effects of the gluten challenge whilst 2 patients on therapy developed blisters, erythema and itching. Serological tests indicated that IgA EmA antibodies and anti-gliadin antibodies after 14 days were not affected significantly, but indicated that abnormally high antibodies titers of both types were present in 8 patients at the start of the trial, suggesting the need for enzyme therapy in addition to the normal gluten-free diet for patient well-being. Conclusions: This study supports the use of enzyme supplementation as a safeguard for patients with DH on a nominal gluten-free diet.

• Klíčová slova
• caricain, endomysiální protilátky IgA, protilátky antigliadinu,
• MeSH
• celiakie MeSH
• dermatitis herpetiformis * diagnóza   dietoterapie   imunologie   krev   patofyziologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• enzymoterapie * MeSH
• enzymy aplikace a dávkování   farmakologie   imunologie   terapeutické užití   MeSH
• gastrointestinální trakt patofyziologie   MeSH
• gluteny * aplikace a dávkování   diagnostické užití   farmakologie   imunologie   škodlivé účinky   účinky léků   MeSH
• histologické techniky metody   využití   MeSH
• imunologické testy metody   využití   MeSH
• interpretace statistických dat MeSH
• kožní manifestace * MeSH
• lidé středního věku MeSH
• lidé MeSH
• ochranné faktory MeSH
• potravní doplňky MeSH
• randomizované kontrolované studie jako téma * MeSH
• senioři MeSH
• sérologie MeSH
• tablety MeSH
• věkové faktory MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Geografické názvy
• Austrálie MeSH
• Polsko MeSH