scholarly journals Gluten Degrading Enzymes for Treatment of Celiac Disease

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2095 ◽  
Author(s):  
Guoxian Wei ◽  
Eva J. Helmerhorst ◽  
Ghassan Darwish ◽  
Gabriel Blumenkranz ◽  
Detlef Schuppan
Keyword(s):  
Celiac Disease ◽  
Enzyme Stability ◽  
Clinical Manifestations ◽  
Cysteine Proteases ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Strict Adherence ◽  
Degrading Enzymes ◽  
Gluten Peptides ◽  
Promising Therapeutic Approach

Celiac disease (CeD) affects about 1% of most world populations. It presents a wide spectrum of clinical manifestations, ranging from minor symptoms to mild or severe malabsorption, and it may be associated with a wide variety of autoimmune diseases. CeD is triggered and maintained by the ingestion of gluten proteins from wheat and related grains. Gluten peptides that resist gastrointestinal digestion are antigenically presented to gluten specific T cells in the intestinal mucosa via HLA-DQ2 or HLA-DQ8, the necessary genetic predisposition for CeD. To date, there is no effective or approved treatment for CeD other than a strict adherence to a gluten-free diet, which is difficult to maintain in professional or social environments. Moreover, many patients with CeD have active disease despite diet adherence due to a high sensitivity to traces of gluten. Therefore, safe pharmacological treatments that complement the gluten-free diet are urgently needed. Oral enzyme therapy, employing gluten-degrading enzymes, is a promising therapeutic approach. A prerequisite is that such enzymes are active under gastro-duodenal conditions, quickly neutralize the T cell activating gluten peptides and are safe for human consumption. Several enzymes including prolyl endopeptidases, cysteine proteases and subtilisins can cleave the human digestion-resistant gluten peptides in vitro and in vivo. Examples are several prolyl endopeptidases from bacterial sources, subtilisins from Rothia bacteria that are natural oral colonizers and synthetic enzymes with optimized gluten-degrading activities. Without exception, these enzymes must cleave the otherwise unusual glutamine and proline-rich domains characteristic of antigenic gluten peptides. Moreover, they should be stable and active in both the acidic environment of the stomach and under near neutral pH in the duodenum. This review focuses on those enzymes that have been characterized and evaluated for the treatment of CeD, discussing their origin and activities, their clinical evaluation and challenges for therapeutic application. Novel developments include strategies like enteric coating and genetic modification to increase enzyme stability in the digestive tract.

Corrigendum: Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients

2017 ◽  
Vol 112 (7) ◽  
pp. 1208
Author(s):  
Isabel Comino ◽  
Fernando Fernández-Bañares ◽  
María Esteve ◽  
Luís Ortigosa ◽  
Gemma Castillejo ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Serological Tests ◽  
Gluten Peptides

An Attempt of Specific Desensitising Treatment with Gliadin in Celiac Disease

2005 ◽  
Vol 18 (4) ◽  
pp. 709-714 ◽  
Author(s):  
G. Patriarca ◽  
N. Pogna ◽  
G. Cammarota ◽  
D. Schiavino ◽  
C. Lombardo ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
Clinical Manifestations ◽  
Current Treatment ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Dietary Regimen ◽  
New Approach ◽  
Tissue Transglutaminase Antibodies

Gluten-free diet is the current treatment of celiac disease. We decided to verify the occurrence of histological and serological modification and/or clinical manifestations during a gradual and progressive introduction of gliadin in the diet and if it may induce a tolerance to food, as it occurs in allergic patients. We studied the case of a celiac woman with complete clinical and histological remittance after 10 years of gluten free diet. She took increasing daily doses of gliadin, reaching the final dose of 9 g of gliadin (15 g of gluten) in 6 months. Then she started a free dietary regimen. During the 15-month follow-up period esophago-gastro-duodenoscopy showed normal Kerckring folds and villi. Anti-gliadin, anti-endomysium and anti-tissue-transglutaminase antibodies, as well as the haematological and biochemical parameters remained normal. Our results represent a new approach in the research concerning celiac disease, and could provide a future line of study for its management.

scholarly journals Non-Invasive Biomarkers for Celiac Disease

2019 ◽  
Vol 8 (6) ◽  
pp. 885 ◽  
Author(s):  
Alka Singh ◽  
Atreyi Pramanik ◽  
Pragyan Acharya ◽  
Govind K. Makharia
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
High Titer ◽  
Invasive Procedure ◽  
Gluten Free Diet ◽  
New Drugs ◽  
Current Status ◽  
Common Disease ◽  
Gluten Free ◽  
Strict Adherence

Once thought to be uncommon, celiac disease has now become a common disease globally. While avoidance of the gluten-containing diet is the only effective treatment so far, many new targets are being explored for the development of new drugs for its treatment. The endpoints of therapy include not only reversal of symptoms, normalization of immunological abnormalities and healing of mucosa, but also maintenance of remission of the disease by strict adherence of the gluten-free diet (GFD). There is no single gold standard test for the diagnosis of celiac disease and the diagnosis is based on the presence of a combination of characteristics including the presence of a celiac-specific antibody (anti-tissue transglutaminase antibody, anti-endomysial antibody or anti-deamidated gliadin peptide antibody) and demonstration of villous abnormalities. While the demonstration of enteropathy is an important criterion for a definite diagnosis of celiac disease, it requires endoscopic examination which is perceived as an invasive procedure. The capability of prediction of enteropathy by the presence of the high titer of anti-tissue transglutaminase antibody led to an option of making a diagnosis even without obtaining mucosal biopsies. While present day diagnostic tests are great, they, however, have certain limitations. Therefore, there is a need for biomarkers for screening of patients, prediction of enteropathy, and monitoring of patients for adherence of the gluten-free diet. Efforts are now being made to explore various biomarkers which reflect different changes that occur in the intestinal mucosa using modern day tools including transcriptomics, proteomics, and metabolomics. In the present review, we have discussed comprehensively the pros and cons of available biomarkers and also summarized the current status of emerging biomarkers for the screening, diagnosis, and monitoring of celiac disease.

Gluten-Related Disorders: Gluten Ataxia

2015 ◽  
Vol 33 (2) ◽  
pp. 264-268 ◽  
Author(s):  
Marios Hadjivassiliou ◽  
David D. Sanders ◽  
Daniel P. Aeschlimann
Keyword(s):  
Age At Onset ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Cerebellar Atrophy ◽  
Gluten Free Diet ◽  
Neurological Dysfunction ◽  
Gluten Free ◽  
Strict Adherence ◽  
Gluten Ataxia ◽  
Antigliadin Antibodies

The term gluten-related disorders (GRD) refers to a spectrum of diverse clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals. They include both intestinal and extraintestinal manifestations. Gluten ataxia (GA) is one of the commonest neurological manifestations of GRD. It was originally defined as otherwise idiopathic sporadic ataxia in the presence of circulating antigliadin antibodies of IgA and/or IgG type. Newer more specific serological markers have been identified but are not as yet readily available. GA has a prevalence of 15% amongst all ataxias and 40% of all idiopathic sporadic ataxias. It usually presents with gait and lower limb ataxia. It is of insidious onset with a mean age at onset of 53 years. Up to 40% of patients have evidence of enteropathy on duodenal biopsy. Gastrointestinal symptoms are seldom prominent and are not a reliable indicator for the presence of enteropathy. Furthermore, the presence of enteropathy does not influence the response to a gluten-free diet. Most patients will stabilise or improve with strict adherence to gluten-free diet depending on the duration of the ataxia prior to the treatment. Up to 60% of patients with GA have evidence of cerebellar atrophy on MR imaging, but all patients have spectroscopic abnormalities primarily affecting the vermis. Recent evidence suggests that patients with newly diagnosed coeliac disease presenting to the gastroenterologists have abnormal MR spectroscopy at presentation associated with clinical evidence of subtle cerebellar dysfunction. The advantage of early diagnosis and treatment (mean age 42 years in patients presenting with gastrointestinal symptoms vs. 53 years in patients presenting with ataxia) may protect the first group from the development and/or progression of neurological dysfunction.

scholarly journals Social Aspects of Adherence to Gluten-Free Diet for Children and Adolescents with Celiac Disease

2021 ◽  
Vol 65 (6) ◽  
pp. 57-64
Author(s):  
I. N. Zakharova ◽  
L. Ja. Klimov ◽  
L. D. Kochneva ◽  
M. G. Gevandova ◽  
V. A. Kuryaninova ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Children And Adolescents ◽  
Social Problems ◽  
Dietary Habits ◽  
Social Issues ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Free Products ◽  
Strict Adherence ◽  
Factors Affecting

The purpose of the study: analysis of medical and social problems and factors affecting the availability and compliance of a gluten-free diet, based on a survey of parents of children with celiac disease living in southern Russia. Purpose of the Study: Analysis of the medical and social problems and factors affecting the availability and adherence to the gluten-free diet based on the results of the questioning survey of the parents of children with celiac disease that are residents of the south of Russia. Children Characteristics and Study Methods. The study include 200 families that bring up the children with the celiac disease at the ages from 10 months to 18 years. The patients included 116 (58%) girls and 84 (42%) boys. The medical and social issues were studied using the developed questionnaire consisting of the open questions and intended as self-administered by the patient parents. Results. 87% of the families noted the significant difficulties in adhering to the diet, 75% were forced to refuse to travel with children, 56% of the surveyed were unable to visit the public spaces, restaurants, and 90% indicated the impossibility and difficulties in purchase of the gluten-free products. The strict adherence to the diet at school age is much worse. The main reasons for the deliberate non- adherence to the gluten-free diet are the high cost of food, lack of funds to purchase it. The patient families spend RUB 8,000– 9,000 per month in average to purchase the gluten-free products. There is a great demand of patients for the imported products with the relevant quality marks. The psychological symptoms were noted in the patients with celiac disease in response to the introduction of the gluten-free diet, manifested by the depression, aggression, irritability, high level of the anxiety. Conclusion. The main difficulties faced by the families that bring up the children and adolescents with the celiac disease include the social and psychological maladjustment of the patients, reduced finances, search and purchase of the high-quality gluten-free products and the necessity to adapt the child and family members to the dietary habits.

scholarly journals Oxidative and Antioxidative Status of Children with Celiac Disease Treated with a Gluten Free-Diet

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Grażyna Rowicka ◽  
Grażyna Czaja-Bulsa ◽  
Magdalena Chełchowska ◽  
Agnieszka Riahi ◽  
Małgorzata Strucińska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Celiac Disease ◽  
Density Lipoprotein ◽  
Gluten Free Diet ◽  
Stress Index ◽  
Healthy Children ◽  
Gluten Free ◽  
Strict Adherence ◽  
Antioxidative Status ◽  
Group I

Aims. Oxidative stress is a factor involved in the pathogenesis of celiac disease (CD), possibly affecting the course of the disease and celiac-related complications. We assessed the intensity of oxidative processes and the efficiency of antioxidant defense in children with celiac disease. Methods. Group I (n=32) consisted of children with CD treated with a gluten-free diet, and group II (n=24) consisted of healthy children on a traditional diet. Antioxidative and oxidative status was assessed by measurement of serum total antioxidant capacity (TAC), total oxidant capacity (TOC), and oxidized low-density lipoprotein (ox-LDL) and on the basis of oxidative stress index (OSI).Results. There were no significant differences in serum TAC, TOC, ox-LDL, and OSI between children with CD and healthy children. Cluster analysis showed that the group of children with CD is not homogeneous in terms of serum TAC and TOC levels. About 50% of these children had TAC levels < 1.3 mmol/L and TOC levels > 0.35 mmol/L.Conclusions. Strict adherence to a gluten-free diet by children with CD seems to be important for maintaining oxidative-antioxidant balance. However, further research is needed to identify factors potentially responsible for increased oxidative stress in some children with celiac disease despite adherence to a gluten-free diet.

scholarly journals Case report: in focus IgA nephropathy as a gluten-related disorder

2021 ◽  
Author(s):  
М.Е. Манцаева ◽  
А.Г. Борисов ◽  
А.А. Стремоухов
Keyword(s):  
Blood Pressure ◽  
Celiac Disease ◽  
Iga Nephropathy ◽  
Tissue Transglutaminase ◽  
Clinical Manifestations ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Related Disorder ◽  
Laboratory Parameters ◽  
Gliadin Peptides

Почки могут вовлекаться в патологический процесс при целиакии как в связи с тяжелыми метаболическими нарушениями, так и в качестве ассоциированного заболевания. В мировой литературе имеются данные о различных типах поражения почек у пациентов с целиакией, включая IgA-нефропатию, диабетическую нефропатию, мембранозную нефропатию, мембранозно-пролиферативный гломерулонефрит, нефротический синдром, связанный с мальабсорбцией, оксалатную нефропатию и ассоциацию целиакии с хронической болезнью почек и терминальной почечной недостаточностью. В статье приводится клинический случай 46-летнего мужчины с выявленным нарушением обмена глютена, заподозренным и диагностированным после верификации хронического гломерулонефрита. Отсутствие характерных клинических проявлений со стороны желудочно-кишечного тракта, повышенные титры антител IgA к тканевой трансглютаминазе и деамидированным пептидам глиадина, морфологическая картина слизистой оболочки 12-перстной кишки не давали оснований в пользу диагноза «целиакия», но указывали на наличие нарушений обмена глютена. Пациенту назначена безглютеновая диета на 6 месяцев. В результате наблюдалось улучшение клинико-лабораторных показателей – более стабильные цифры артериального давления на стандартной гипотензивной терапии, снижение суточной протеинурии, гематурии и титров антител IgA к тканевой трансглютаминазе и деамидированным пептидам глиадина. Очевидно, что введение безглютеновой диеты в рацион пациентов с IgA-нефропатией может улучшить клинико-лабораторные показатели, такие как артериальное давление, суточная протеинурия, гематурия, и, вероятно, отсрочить прогрессирование хронической болезни почек. The kidneys can be involved in the pathological process in celiac disease, both in connection with severe metabolic disorders, and as an associated disease. In total, there is evidence of various types of kidney damage in patients with celiac disease, including IgA nephropathy, diabetic nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, nephrotic syndrome associated with malabsorption, oxalate nephropathy, and the association of celiac disease with chronic renal disease and terminal renal insufficiency in the literature. We describe a case of a 46-year-old man with gluten-related disorders. Given the absence of typical clinical manifestations from the gastrointestinal tract, increased antibodies IgA to tissue transglutaminase and deamidated gliadin peptides, the morphological picture of the duodenal mucosa, do not give grounds for diagnosing celiac disease, but indicate the presence of a gluten-related disorders in the patient. The patient was prescribed a gluten-free diet for a period of 6 months. As a result, an improvement in clinical and laboratory parameters was observed: more stable blood pressure values on standard antihypertensive therapy, a decrease in proteinuria, hematuria, and antibody IgA to tissue transglutaminase and deamidated gliadin peptides. The introduction of a gluten-free diet in the diet of patients with IgA-nephropathy can improve clinical and laboratory parameters, such as blood pressure, proteinuria, hematuria, and probably delay the progression of chronic renaldisease.

scholarly journals Probiotic supplement and gluten withdrawal in gluten allergy Patients may lead to gluten tolerance: first case report

2021 ◽  
Vol 8 (7) ◽  
pp. 3603
Author(s):  
Moni Kumari ◽  
Renu Bansal ◽  
Ranjit Singh ◽  
Parveen Bansal ◽  
Malika Arora
Keyword(s):  
Celiac Disease ◽  
Case Report ◽  
Disease Patient ◽  
Celiac Disease Patient ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Probiotic Supplementation ◽  
Strict Adherence ◽  
First Case ◽  
The Subject

Probiotic species such as lactobacillus and bifidobacteria are known to have a major role in gluten digestion and regulation of proper functioning of gastrointestinal system however these are found to be missing in gluten allergy patients. So, here in this case we aimed to find the effect of probiotic supplementation along with gluten free diet in celiac disease patient. A case of an 8-year-old female child admitted to civil hospital, Faridkot with chief complaints of vomiting, diarrhea, weight loss, retarded growth, and malnutrition was studied. When she first visited the hospital, based on her symptoms, she was advised celiac disease workup and was found to be highly tTG IgA positive (10.62). The subject was shifted to a strict gluten free diet along with probiotic supplementation. The subject was regularly followed up for the period of four and half years in order to find improvement in her symptoms. After 4 years, gluten diet was gradually reintroduced in a phased manner; the patient remained well even on full gluten diet. This may be due to probiotic supplementation to the subject along with gluten free diet. Present case report describes the spontaneous recovery of celiac disease patient after strict adherence to gluten free diet and probiotic supplementation for a specified period. It is suggested that there should be a proper monitoring and detailed evaluation of clinical and histological markers of recovery in a patient after strict adherence to gluten free diet and probiotic supplementation in order to evaluate the possible role of probiotic supplements in the management of CD.

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