Strict Gluten-free Diet Research Articles

Nutrition Assessment and Management in Celiac Disease

Celiac disease (CeD) is the most common immune condition affecting the gastrointestinal tract; it is triggered by gluten and the only available treatment is a strict gluten-free diet (GFD). Therefore, for patients with CeD, adopting a GFD is not a lifestyle choice. The major problem is that a GFD is restrictive and, like all restrictive diets, it has the potential for adverse nutritional outcomes, especially if adopted for a long term. It is well known that GFD can be nutritionally inadequate and is frequently associated with vitamin and mineral deficiencies; it is also associated with excessive sugar and fat intake, particularly when gluten-free substitutes are consumed. Consequently, people with CeD are affected by higher rates of overweight and obesity and metabolic complications, such as fatty liver and cardiovascular disease. Therefore, assessment of nutritional status and diet quality at diagnosis and while on a long-term GFD is key in the management of CeD. This narrative review addresses nutritional considerations in CeD and management of common challenges associated with a GFD.

Pacientų, turinčių celiakijos sukeltų neurologinių simptomų, diagnostikos ir gydymo galimybės

Celiac disease (CD) is a gastrointestinal disorder caused by the immune system’s response to gluten, involving both innate and adaptive immune reactions. It leads to various neurological issues, such as gluten ataxia, gluten neuropathy, epilepsy, and gluten encephalopathy. Although neurological presentations are rare in children, they are observed in up to 36% of adult patients with CD. Recent evidence suggests that these manifestations may be linked to gluten-related mechanisms, including antibody cross-reactions, immune-complex deposition, direct neurotoxicity, and, in severe cases, vitamin or nutrient deficiencies. However, there is still no consensus on whether serological, neurophysiological, or neuroimaging findings can effectively diagnose and monitor CD-associated neurological problems at an early stage. The identification of multimodal biomarkers and suitable neuroimaging tools could aid in the diagnosis, monitoring, and enhancement of the quality of life for individuals with neuroceliac disease. Nonetheless, it is essential to provide appropriate treatment to those with CD and neurological symptoms, as prolonged suffering may lead to irreversible disability. The primary treatment for neurological manifestations of gluten-related disorders is a strict gluten-free diet, although a small number of patients may require additional immunosuppressive therapy, typically using mycophenolate or intravenous immunoglobulins. In this literature review, our aim was to explore the relevant neurological disorders associated with CD, early diagnostic and treatment options to prevent related disability in affected patients. Clinicians should consider CD as a potential cause in individuals presenting with unexplained neurological dysfunction.

Biochemical Markers of Iron Status Among Iraqi Patients at Different Severity Levels of Celiac Disease

In people with a hereditary predisposition, gluten consumption causes celiac disease, a multifactorial autoimmune condition. The ensuing small intestine inflammatory process develops specific antibodies and causes various gastrointestinal and extra-intestinal symptoms with varying degrees of severity. Evaluation of the blood iron profile at various histological celiac disease severity in Iraqi patients was the goal of the current study. Seventy-five Iraqi patients with celiac disease, with a mean age of 18.68± 11.13 years, were the study's participants. These people tested positive for celiac antibodies and experienced gastrointestinal symptoms. Based on the disease histological severity, they were divided into two groups: marsh (III a, b, c) group and marsh (0, I) group. For comparison purposes, 46 people who appeared to be in good health and matched in age and gender to the patients utilized in the study were also included. The levels of iron, transferrin, hemoglobin, ferritin, total iron binding capacity, unsaturated iron binding capacity, and the percentage of transferrin that is saturated with iron were all measured. In comparison to the other patient groups under study, celiac patients (marsh III) group, and particularly those of group (marsh III c), showed a substantial drop (p<0.05) in iron, the percentage of transferrin saturating with iron, the levels of each ferritin and of hemoglobin. The total iron binding capacity and the unsaturated iron binding capacity showed a significant elevation (p<0.05) in (marsh III c) patients’ group, meanwhile non-significant differences (p> 0.05) were found in transferrin concentration. Moreover, significant differences (p< 0.05) were obtained in the iron profile between celiac patients who followed strict gluten free diet and those patients with gluten contained diet.

Assessing Parents Knowledge of Coeliac Disease: A Prospective Study of 70 Cases

Background: Celiac disease is treated by following a strict gluten-free diet for life. Following this diet is practically difficult and the patient requires appropriate management.

A176 RESTORATION OF IMPAIRED MICROBIOTA-MEDIATED ARYL HYDROCARBON RECEPTOR SIGNALING IN PATIENTS WITH CELIAC DISEASE BY ORAL TRYPTOPHAN SUPPLEMENTATION: AN EXPLORATORY STUDY

Abstract Background Celiac disease (CeD) is an autoimmune condition driven by gluten in individuals expressing celiac-specific genes (HLA-DQ2 and/or DQ8). A strict gluten-free diet (GFD) is currently the only treatment. 30-40% of celiac patients exhibit persistent symptoms despite following a GFD ampersand:003E1 year and are considered non-responsive. Tryptophan is an essential amino acid metabolized by gut microbiota to produce indoles that activate aryl hydrocarbon receptor (AhR), contributing to intestinal barrier homeostasis. Our previous study showed CeD patients have altered tryptophan metabolism and limited AhR activation, only partially improving with a GFD. In healthy volunteers, oral tryptophan supplementation improved AhR activation in the small intestine, thus, indicating its feasibility as adjuvant to the GFD in non-responsive CeD. Aims The study aims were to: 1) determine whether tryptophan supplementation improves celiac specific symptoms in non-responders; and 2) if tryptophan supplementation modifies gut microbiota composition, intestinal indole production and AhR activity. Methods The study is a double-blind, randomized, placebo-controlled trial with the aim to recruit 50 adults from the McMaster University Celiac Clinic. At visit 1, consented participants are randomized 1:1 to L-tryptophan (3g/day) or placebo and receive intervention capsules to be taken for 3 weeks after Visit 2. At Visits 2 and 3, participants complete dietary and symptom questionnaires, provide blood, stool, and urine samples, and undergo endoscopy. The primary outcome, improvement in symptoms, is assessed using the Celiac Symptoms Index (CSI); general GI symptoms by Gastrointestinal Symptoms Rating Scale (GSRS); mood symptoms by Hospital Anxiety and Depression Scale (HADS); quality of life by Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life questionnaire (PAGI-QoL). Results To- date we have recruited 10 participants. We will present blinded results from participants that have completed the study at the time of presentation based on responses to questionnaires pre, and post tryptophan/placebo intervention. At the time of analysis of this abstract, 5 participants had completed the study showing reduced CSI scores post intervention. The GSRS was also significantly reduced post intervention however, no change was observed in HADS and PAGI-QoL. Conclusions As all these results are currently blinded, we cannot attribute the symptom improvement to either tryptophan or the placebo effect. After unblinding the data, we will analyze the data to determine the extent of symptom reduction in relation to tryptophan metabolites (from urine, stool and duodenal aspirates) and AhR activation (from duodenal biopsy samples). Funding Agencies Weston Family Foundation

A19 THE IMPACT OF FOOD INSECURITY ON ADHERENCE TO A GLUTEN-FREE DIET IN THE ADULT CELIAC DISEASE POPULATION ATTENDING A DEDICATED CELIAC CLINIC

Abstract Background A strict gluten-free diet (GFD) is currently the only treatment for celiac disease (CeD), but a GFD can be inconvenient and expensive. CeD patients who are food insecure (FI) face threats to GFD adherence, overall health, and quality of life. Aims To evaluate the prevalence of FI in patients with CeD attending a dedicated Adult Celiac Disease Clinic (ACDC) at an academic hospital and to examine the relationship between FI and GFD adherence, quality of life and various gastrointestinal symptoms. Methods Patients were invited to participate in the CeD registry when they attended the ACDC; those who agreed to participate then provided verbal and signed consent. Patients had the option to complete the CeD registry forms in the clinic on an iPad or at home using a card with a QR code and a unique ID to access the online CeD registry. The CeD registry uses REDCap (v. 11.1, 2021, US) and includes six validated questionnaires (Celiac Diet Adherence Test (CDAT), Celiac Disease Quality of Life Questionnaire (CD QoL), Celiac Symptom Index (CSI), Gastrointestinal Symptom Rating Scale (GSRS), Hospital Anxiety and Depression Scale (HADS), and Household Food Security Survey Module (HFSSM)). Continuous data are expressed as mean (SD), and categorical data as proportions of patients. The chi-squared test with Fisher correction and t-test were used to assess differences between groups. Results A total of 653 patients attended the ACDC from November 2, 2022, to September 20, 2023, and 411 patients were invited to participate in this study. Of them, 204 completed the CeD registry. Food insecurity was identified in 16% of CeD patients, of whom 11 (5%) were marginally FI, 16 (8%) were moderately FI, and 7 (3%) were severely FI. Compared to CeD patients who are food secure, a greater proportion of FI CeD patients reported nonadherence to GFD (26/34 vs 70/170; p<0.001), reduced QoL (32/34 vs 98/170; p<0.001), greater anxiety (27/34 vs 84/170; p=0.001) and greater depression (13/34 vs 26/170; p=0.004) compared with normal values. CeD patients with FI also reported lower QoL [61.0(14.9) vs 49.6(16.7); p=0.001] and increased gastrointestinal symptoms [GSRS 37.7(14.7) vs 29.0(12.8); p=0.001] compared with food secure CeD patients. Conclusions Food insecurity is common in patients with CeD and is associated with significantly worse adherence to treatment, symptom control, and quality of life. There is an important need for programs and societal measures to abolish food insecurity and ensure adequate access to treatment for patients with CeD. Funding Agencies TRIANGLE Summer Studentship

A69 EXPANDED ROLE OF THE DIETITIAN IN THE CLINICAL MANAGEMENT OF PATIENTS WITH CELIAC DISEASE

Abstract Background The only available treatment for Celiac Disease (CeD) is adhering to a strict gluten-free diet (GFD). However, a GFD has been associated with multiple nutrient imbalance and deficiencies, which are often under-recognized and remain untreated. Aims To identify the reasons for referral to a registered dietitian (RD) and RD-recommended dietary interventions for patients with CeD attending a specialised Adult Celiac Disease Clinic. Methods We conducted a retrospective chart review using nutrition assessment forms completed by the RD between November 2021 and May 2022. CeD diagnosis was performed through specific serology (anti-tissue transglutaminase IgA and anti-deamidated gliadin peptide IgG) and confirmed by duodenal biopsies demonstrating villous atrophy. We collected data on demographics, diagnosis date, nutritional status (BMI), micronutrients measured in serum, gastrointestinal (GI) symptoms, reason for consult, and the recommendations made by the RD. Data was collected in RedCap (v. 11.1, 2021, US) and expressed as both a proportion and Median (IQR). Results A total of 136 visits from 102 patients were included in the analysis. Of them, 77 were female (75.5%) with a mean age of 40.3 yrs (+/- 16.0). The median year of CeD diagnosis was 4 (IQR= 6) from 2002-2022. Patients reported various symptoms including bloating (50.9%), abdominal pain (34.3%), and constipation (23.5%). 56% of patients were overweight or obese (BMI ampersand:003E25), and 4.9% were undernourished (BMIampersand:003C18). The most common nutrient deficiencies were ferritin below 30 ng/mL (58.8%), zinc below 9.4 µmol/L (23.5%), and suboptimal levels of vitamin D (38.2%). The most common reasons for referral to the RD were to assess GFD adherence (44.1%), dietary management of GI symptoms (30.4%) and nutritional optimization (24.5%). We identified 18 different interventions recommended by the RD, the most common being how to prevent gluten cross-contamination (58.8%), tips for dining out (43.1%), GF diet education (32.4%), and increasing fibre intake (30.4%). The most common reasons for follow up visits (n=34) included dietary management of GI symptoms (60.9%) and GFD adherence (43.5%). Conclusions Patients with CeD face multiple nutritional challenges associated with following a GFD, and a number of GI symptoms. Although the GFD is the only available treatment, this review identifies the need for multiple individualized dietary interventions, which require and encourage the inclusion of a specialized RD to ensure personalized, effective care and support in the management of CeD. Funding Agencies None

Celiac Disease: Promising Biomarkers for Follow-Up.

Celiac disease is a common gastroenterological illness. Current diagnostics of the disease are based on serological markers and histology of duodenal biopsies. Hitherto, a strict gluten-free diet is the only effective treatment and is necessary for good control of the disease. Serological tests in current use have very high specificity and sensitivity for diagnostics, but in follow-up they have some limitations. Their levels do not accurately reflect mucosal healing, and they are unable to detect minimal transgressions in the diet. This problem is significant in patients with IgA deficiency, and there exist no robust follow-up tools for monitoring these patients' adherence to treatment. For their follow-up, we currently use IgG-based tests, and these antibodies persist for a long time even when a patient has stopped consuming gluten. More accurate and specific biomarkers are definitely needed. Adherence to a gluten-free diet is essential not only for intestinal mucosa healing and alleviation of symptoms but also for preventing complications associated with celiac disease. Here, we summarize current evidence regarding noninvasive biomarkers potentially useful for follow-up not only of patients with IgA deficiency but for all patients with celiac disease. We describe several very promising biomarkers with potential to be part of clinical practice in the near future.

THU437 Oral Ulcers As A Clue To Bone Fragility

Abstract Disclosure: S. Sridhar: None. E.I. Krug: None. Introduction: Metabolic bone disease is common in celiac disease (CD) and can occur in patients without gastrointestinal symptoms. Successful treatment of malabsorption is associated with amelioration of bone loss. Recurrent aphthous stomatitis (RAS) may be the sole manifestation of CD (1). According to American College of Gastroenterology Guidelines, tissue transglutaminase (tTG)-IgA antibody and total IgA level is the single preferred test for detection of CD in adults due to reported sensitivity of 90-98% and specificity of 95-97%. No additional testing is typically recommended for patients without IgA deficiency (2). Case: The patient is a 58 year old woman with past medical history of RAS treated with prednisone, 5 mg daily for 10 years, facial and ocular rosacea, menopause at age 49, asthma, chronic back and neck pain, history of spontaneous rib fracture and L4 compression fractures during chiropractic manipulation, who had progressive bone loss despite ongoing treatment with oral bisphosphonates, calcium and vitamin D supplementation for 4 years with good adherence, and was referred for endocrine evaluation. Laboratory studies revealed TSH 1.94 mIU/L (0.4-4.5), 25(OH)vit D 41 ng/mL (30-100 ng/mL), PTH 31 pg/mL (14-64), Ca 9. mg/dL (8.6-10.4), albumin 4.1 mg/dL (3.6-5.1), Mg 2.1 mg/dL (1.5-2.5), tTG-IgA 1 U/mL (<4), total IgA 190 mg/dL (47-310), Gliadin deamidated peptide IgA Ab 11 Units (<20), Gliadin deamidated peptide IgG Ab (DGP-IgG) 44 Units (<20). Duodenal biopsy revealed diffuse increase in intraepithelial lymphocytes, acute and chronic inflammation of lamina propria, focally marked villous blunting consistent with CD. The patient reported complete resolution of RAS and rosacea symptoms within one month of starting a strict gluten free diet. She also noted marked improvement in neck and back pain. After 6 months repeat DGP-IgG was 13 Units. Treatment with teriparatide of 12 months duration resulted in 12.1% and 5.4% gain in bone density of lumbar spine and total hip respectively. Conclusion: CD should be suspected in patients with osteoporosis and extraintestinal conditions including RAS and, possibly, rosacea. CD has been reported in 2.83% of 247 patients with RAS screened for (tTG)-IgA and anti-endomysial IgA Abs (2). Rosacea has also been linked to CD in one study (3). Our case suggests that patients presenting with RAS may need to be tested for DGP-IgG reported to have a sensitivity of 92% and specificity of 100%, regardless of total IgA level.

Associations between executive functioning and adherence in pediatric celiac disease

ABSTRACT A strict gluten-free diet is the only treatment for celiac disease (CD), yet dietary adherence can be challenging for youth and may be impacted by the youth’s executive functioning and attentional abilities. This study aimed to investigate whether attention and executive functioning (EF) were associated with dietary adherence in children with CD. Parents of 34 children (child age M(SD) = 13.01(3.88), 56% female) from a multidisciplinary CD clinic completed ratings of attention and EF and dietary adherence. Parent-reported adherence was negatively correlated with behavioral regulation (r = -.52, p < .01, r 2 = .27, 95% confidence interval (CI) [−.73, −.22]) and cognitive regulation (r = -.48, p < .01, r 2 = .23, 95% CI [−.71, −.17]), with an interaction by age (p = .01, adjusted R 2 = .35, B = −0.15, 95% CI [−0.29, −0.07]) for behavior regulation. Youth who were rated as less adherent by their parents were rated as having more problems with behavioral (e.g. inhibition and self-monitoring) and cognitive regulation (e.g. planning, organization), and adolescents with lower parent-rated adherence were rated as having more problems with behavioral regulation in particular. Executive functioning deficits are an important treatment consideration for CD, particularly during adolescence.

Cross-sectional imaging: current status and future potential in adult celiac disease.

Celiac disease (CD), triggered by exposure to gluten in genetically susceptible individuals, is an immune-mediated small bowel disease affecting about 1% of the population worldwide. But the prevalence of CD varies with age, sex, and location. A strict gluten-free diet remains the primary treatment for CD, currently. Most of patients with CD respond well to gluten-free diet with good prognosis, while some patients fail to get symptomatic relief or histological remission (e.g., nonresponsive or refractory CD). Because of heterogeneous clinical appearance, the diagnosis of CD is difficult. Moreover, malignant complications and poor outcomes accompanied with refractory CD present great challenges in disease management. Over the past three decades, cross-sectional imaging techniques (computed tomography [CT] and magnetic resonance imaging [MRI]) play an important role in small bowel inflammatory and neoplastic diseases. Compared with endoscopic techniques, cross-sectional imaging permits clearly presentation of both intraluminal and extraluminal abnormalities. It provides vascular and functional information, thus improving the possibility as diagnostic and follow-up tool. The value of cross-sectional imaging for patients with suspected or confirmed CD has been gradually demonstrated. Studies revealed that certain features suggested by cross-sectional imaging could help to establish the early diagnosis of CD. Besides, the potential contributions of cross-sectional imaging may lie in the evaluation of disease activity and severity, which helps guiding management strategies. The purpose of this review is to provide current overviews and future directions of cross-sectional imaging in adult CD, thus facilitating the understanding and application in clinical practice. CLINICAL RELEVANCE STATEMENT: In this review, we systematically summarized the existing knowledge of cross-sectional imaging in adult CD and analyzed their possible roles in clinical practice, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. KEY POINTS: • Regarding a condition described as "celiac iceberg", celiac disease remains underdiagnosed and undertreated. • Cross-sectional imaging is helpful in clinical management of celiac disease, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. • Cross-sectional imaging should be considered as the valuable examination in patients suspected from celiac disease.

Enhancing gluten detection assay development through optimization of gliadin extraction conditions

Gluten consumption can lead to severe health conditions in certain individuals, and following a strict gluten-free diet is often the only effective treatment option. Therefore, it is crucial to develop a gluten detection method that is accurate, sensitive, and specific to ensure the absence of gluten. An important aspect of developing effective gluten detection tests is the implementation of an efficient gluten extraction method. In this study, we conducted an evaluation of various buffer conditions for gliadin extraction from both heat-treated and non-heat-treated food samples. These buffer conditions included ethanol, 2-mercaptoethanol, guanidine hydrochloride, detergents, chelating agents, and deep eutectic solvents. Among the tested conditions, a combination of 2-mercaptoethanol and guanidine hydrochloride demonstrated significantly higher extraction efficacy compared to most other conditions. Furthermore, we explored the use of a less toxic extraction buffer, choline chloride, which exhibited a 1.4-fold higher extraction efficiency than the combination of 2-mercaptoethanol and guanidine hydrochloride (p < 0.05). Choline chloride showed great potential as a preferred buffer for commercial gliadin extraction kits, suitable for both heat-treated and non-heat-treated food samples. Overall, our findings highlight the importance of optimizing the gluten extraction process to improve the accuracy and reliability of gluten detection methods, ultimately contributing to the development of effective tools for individuals following a strict gluten-free diet.

Uncovering the Concerns and Needs of Individuals with Celiac Disease: A Cross-Sectional Study.

The treatment for celiac disease (CD) involves a strict gluten-free diet, which can be challenging and lead to questions for patients. Pinpointing these uncertainties can enable the creation of efficient educational resources. In this study, a questionnaire was specifically designed to gain insights into the knowledge, concerns, and needs of individuals with CD and their supporters. The questionnaire was distributed through the Instagram social network and received adequate responses from 300 participants, 258 (86%) being female and 152 (50.7%) falling in the age range of 25-44 years. The concerns of individuals with celiac disease and celiac supporters were rated on a 1-4 scale, with a mean score of 3.5 indicating significant concern. A total of 255 (85%) of all participants expressed that their principal concern was the social limitations they faced, such as difficulties in eating out and sharing food with others. Every participant evaluated their overall disease knowledge, averaging at 2.92 out of 4, indicating a reasonable level of awareness. When asked if they believed that improving general knowledge about CD in the general population would enhance their quality of life, the vast majority responded affirmatively. This finding underscores the importance of not only educating individuals with CD but also reaching out to the wider population, especially those who have a direct impact on the daily lives of individuals with CD, such as family members, friends, and food service providers.

Old and New Adjunctive Therapies in Celiac Disease and Refractory Celiac Disease: A Review.

Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only recommended treatment. However, unintentional gluten ingestion or a persistent villous atrophy with malabsorption (regardless of a strict GFD) as in the case of Refractory Celiac Disease (RCD) represents a major issue. In this review, we have analysed and discussed data from both randomized controlled trials and observational studies concerning adjunctive therapies as well as novel therapies for the treatment of CD and RCD. The literature search was carried out through Medline and Scopus. In total, 2268 articles have been identified and 49 were included in this review (36 studies resulting from the search strategy and 13 from other sources). Today, GFD remains the only effective treatment, although steroids, mesalamine, and more recently biological therapies have found space in the complex management of RCD. Currently, studies evaluating the effectiveness of novel therapies are still limited and preliminary results have been controversial.

Spontaneous Recovery of Isolated Advanced Heart Block in Patient with Celiac Disease by Starting a Strict Gluten Free Diet: A Case Report and Review of the Literature.

Celiac disease is a malabsorptive long-term autoimmune disorder where the small intestine is the primarily affected organ due to gluten intolerance and affects 1% of the general population.Cardiovascular pathology, including dilated cardiomyopathy, myocarditis, arrhythmias, and premature atherosclerosis, was found to be more prevalent in patients with celiac disease than in others without celiac disease.The association of celiac disease with isolated advanced atrioventricular conduction abnormality is rare and a gluten-free diet may help improve the conduction abnormality.

Celiac disease: Pathogenesis, disease management and new insights into the herbal-based treatments.

Celiac disease (CD) is a gluten intolerance autoimmune disorder which its symptoms involve the gastrointestinal tract and sometimes the other organs. It is one of the most prevalent health problems rising in many populations as statistics show that in every 100 people about one person is suffering from CD. It has been observed that the persons who genetically contain the human leukocyte antigen (HLA) DQ2 and HLA DQ8 genes involved in the immune system haplotypes are more prone to develop an allergy to gluten. The only treatment currently available for CD is a strict gluten-free diet. However, recent research has shown promising new insights into the herbal-based treatments of CD. New insight on CD is now offering various prospects to manage its treatment, diagnosis, and serving in the development of advanced therapies. Several herbs and botanical extracts have demonstrated anti-inflammatory, immunomodulatory, and gut-healing properties that make them potential candidates for the management of CD. Here, we provide an updated review on pathogeneses and managements of CD. In particular, we summarize the current understandings of herbal-based treatments for CD and highlights their potential benefits.

In vitro Gluten Degradation Using Recombinant Eurygaster Integriceps Prolyl Endoprotease: Implications for Celiac Disease.

Celiac disease (CD) is a gluten-sensitive chronic autoimmune enteropathy. A strict life-long gluten-free diet is the only efficient and accepted treatment until now. However, maintaining a truly gluten-free status is both difficult and costly, often resulting in a social burden for the person. Moreover, 2 to 5 percent of patients fail to improve clinically and histologically upon elimination of dietary gluten. Therefore, novel therapeutic approaches, including gluten degrading enzymes, are an unmet need of celiac patients. To evaluate the function of sunn pest prolyl endoprotease for gluten and gliadin hydrolysis in vitro. The spPEP was expressed as a recombinant protein in E. coli BL21 (DE3), and its catalytic activity was assessed by SDS-PAGE and RP-HPLC analyses. Production of a 100-kDa spPEP protein was confirmed by SDS-PAGE and western blot analysis. Also, we demonstrate that spPEP efficiently degrades gluten and α-gliadin (30-40 kDa) in vitro under conditions similar to the GI and is resistant to pepsin and trypsin. The gathered data demonstrated that spPEP might be a novel candidate for Oral Enzymatic Therapy (OET) in CD and other gluten-related disorders.

The effect of gluten-free diet on mean platelet volume levels as a short-term follow up biomarker in biopsy proven celiac disease patients and its comparison with IgA-tissue transglutaminase antibody levels

Background: Celiac disease is an autoimmune disease for which there is a known environmental trigger i.e., gluten. Adherence to gluten-free diet is the mainstay of treatment. Methods: This observational prospective study was conducted in the Department of Paediatrics, SP Medical College, Bikaner between August 2020 to August 2021. Newly diagnosed celiac disease patients below 14 years of age were included in the study excluding patients with any associated co-morbid conditions like Diabetes, Hypertension and Hypothyroidism. IgA-tTG titre and complete blood counts were performed at the time of diagnosis, and repeated after 3 months of strict gluten-free diet. The collected data were coded, tabulated and analysed. P values &lt; 0.05 were statistically significant. Results: The mean IgA-tTG decreased from 116.28 at the time of diagnosis to 50.98 after 3 months of the gluten-free diet (p = &lt;0.001). Also, the mean MPV decreased from 9.58 to 9.19 and the change was statistically significant (p = 0.032). When two biomarkers i.e., MPV and IgA-tTG were compared as being better biomarkers for the gluten-free diet, a weak positive correlation was observed but was not statistically significant (p = 0.212). Conclusions: This study showed that Mean Platelet Volume (MPV) levels can be used as a short-term biomarker to check adherence to the gluten-free diet.

P12 A flare of dermatitis herpetiformis precipitated by etanercept

Abstract We report the case of a 79-year-old man who presented with an acute, intensely pruritic, widespread rash, which, on examination, consisted of symmetrical, haemorrhagic nodules and vesicles with some desquamation affecting the extensor surfaces of the arms, flexor surfaces of the legs and the natal cleft. He had a history of coeliac disease (for which he had adhered to a strict gluten-free diet since 1997) and rheumatoid arthritis. He had his first dose of the anti-tumour necrosis factor (TNF) agent etanercept prior to this episode to manage his arthritis. A punch biopsy for histopathology showed subepidermal blisters with a predominance of neutrophils. Eosinophils were also present to the level of the eccrine coils within the dermis, with eosinophilic flame figures but no eosinophil spongiosis at the edges of the blister. Direct immunofluorescence showed granular IgM and IgA in the dermal papillae, and a similar reaction was seen with fibrinogen. These histological findings were strongly suggestive of dermatitis herpetiformis (DH). Owing to diagnostic uncertainty on presentation, initial treatment was with high-dose topical steroids and emollient. and a yellow card was completed. Since this presentation, he has had no further flares and has not required dapsone. Multidisciplinary team discussion decided that the patient should avoid other anti-TNF treatments, but he has found relief for multiple months with rituximab and has had no cutaneous adverse events on this agent. The aetiology of DH following anti-TNF treatment is not immediately clear. Increased immunogenicity and cytokine release have been hypothesized to be part of the pathology of many adverse reactions to anti-TNF agents. It is conceivable that the cytokine release ordinarily seen in DH is replicated by the administration of anti-TNF agents. There have been many cases of anti-TNF agents leading to worsening eczema and psoriasis. Interestingly, these conditions have been found to upregulate TNF-α, a feature that is also seen in DH. This appears to be the first case described in the literature of etanercept-induced DH. A reaction with infliximab was reported in 2008, with a similar rash and histology consistent with DH, but it differed as the patient had no prior diagnosis of coeliac disease and presented after their second dose (Marakli SS, Uzun S, Ozbek S, Tuncer I. Dermatitis herpetiformis in a patient receiving infliximab for ankylosing spondylitis. Eur J Dermatol 2008; 18:88–9).

Exploring novel therapies for coeliac disease: are safe drugs tolerable?

Coeliac disease is the only autoimmune condition where the main environmental trigger, gluten, is known. 1 Catassi C Verdu EF Bai JC Lionetti E Coeliac disease. Lancet. 2022; 399: 2413-2426 Summary Full Text Full Text PDF PubMed Scopus (36) Google Scholar Adherence to a strict gluten-free diet for life is essential for intestinal mucosal recovery, alleviation of symptoms, and to reduce the risk of complications such as anaemia, osteoporotic fractures, and small bowel cancer. 2 Kivelä L Caminero A Leffler DA et al. Current and emerging therapies for coeliac disease. Nat Rev Gastroenterol Hepatol. 2020; 18: 1-15 Google Scholar However, strict long-term compliance with a gluten-free diet can be socially inconvenient and expensive. 3 Pinto-Sanchez MI Verdu EF Gordillo MC et al. Tax-deductible provisions for gluten-free diet in Canada compared with systems for gluten-free diet coverage available in various countries. Can J Gastroenterol Hepatol. 2015; 29: 104-110 Crossref PubMed Scopus (21) Google Scholar Moreover, up to 30% of people with coeliac disease continue to have symptoms despite attempting the strict diet 4 Penny HA Baggus EMR Rej A et al. Non-responsive coeliac disease: a comprehensive review from the NHS England National Centre for Refractory Coeliac Disease. Nutrients. 2020; 12: 216 Crossref PubMed Scopus (43) Google Scholar , and almost 80% indicated a desire for therapy to liberalise their diet. 5 De Leon Morilla D Ventoso M Lebovits J et al. Patients' risk tolerance for non-dietary therapies in celiac disease. Clin Gastroenterol Hepatol. 2022; 20: 2647-2649 Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Therefore, emerging therapies to support the gluten-free diet, including those targeting induction of tolerogenic mechanisms, are currently being investigated in clinical trials. 6 Pinto-Sanchez MI Silvester JA Lebwohl B et al. Society for the Study of Celiac Disease position statement on gaps and opportunities in coeliac disease. Nat Rev Gastroenterol Hepatol. 2021; 18: 875-884 Crossref PubMed Scopus (13) Google Scholar Safety and tolerability of KAN-101, a liver-targeted immune tolerance therapy, in patients with coeliac disease (ACeD): a phase 1 trialKAN-101 has an acceptable safety profile in patients with coeliac disease with no dose-limiting toxicities and no maximum tolerated dose was observed. Rapid systemic clearance of KAN-101 was observed and no accumulation on repeated dosing. A future study will evaluate the safety and efficacy, including biomarker responses with a gluten challenge, of KAN-101 at doses 0·6 mg/kg and greater in patients with coeliac disease. Full-Text PDF