Investigation of molecular markers in the diagnosis of refractory coeliac disease in a large patient cohort: Table 1

2008 ◽  
Vol 61 (11) ◽  
pp. 1200-1202 ◽  
Author(s):  
U O’Shea ◽  
M Abuzakouk ◽  
C O’Morain ◽  
D O’Donoghue ◽  
K Sheahan ◽  
...  
Keyword(s):  
Molecular Markers ◽  
T Cell ◽  
Coeliac Disease ◽  
Cell Population ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Histological Lesion ◽  
Strict Adherence ◽  
Small Intestinal ◽  
Refractory Coeliac Disease

Aims:Some patients with coeliac disease, despite strict adherence to a gluten-free diet, continue to have significant symptoms and/or a severe small intestinal histological lesion. The term “refractory coeliac disease” (rCD) is used to describe this condition. The purpose of this study was to investigate the value of tissue molecular markers reported to help in the diagnosis of rCD.Methods:Details on 61 patients with suspected rCD were collected. The clinical and laboratory findings in these patients were carefully evaluated, in part to determine whether patients were adhering to a strict gluten-free diet. The co-expression of CD3 and CD8 on intraepithelial lymphocytes was investigated by monoclonal antibody staining of small intestinal biopsy tissue; a finding of less than 50% CD3+ cells co-expressing CD8 was defined as an aberrant phenotype. T cell receptor gene rearrangement was assessed when a sufficient tissue sample was available.Results:A diagnosis of rCD was made in 38 patients based on clinical, laboratory and histological data. An aberrant intraepithelial lymphocyte population was found in 20 of these patients and in this group a clonal T cell population was found in five of seven patients tested. In the remaining 18 patients, the CD3/CD8 ratio was normal and two of seven tested had a clonal T cell population. After detailed monitoring, a diagnosis of rCD was excluded in the remaining 23 patients.Conclusions:This study supports the use of phenotypic and T cell clonality investigations in identifying patients with true rCD.

scholarly journals Differential IL-13 Production by Small Intestinal Leukocytes in Active Coeliac Disease versus Refractory Coeliac Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Sascha Gross ◽  
Roy L. van Wanrooij ◽  
Petula Nijeboer ◽  
Kyra A. Gelderman ◽  
Saskia A. G. M. Cillessen ◽  
...  
Keyword(s):  
Coeliac Disease ◽  
Potential Role ◽  
Cytokine Production ◽  
Villous Atrophy ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Strict Adherence ◽  
Aberrant Phenotype ◽  
Small Intestinal ◽  
Production Pattern

A small fraction of coeliac disease (CD) patients have persistent villous atrophy despite strict adherence to a gluten-free diet. Some of these refractory CD (RCD) patients develop a clonal expansion of lymphocytes with an aberrant phenotype, referred to as RCD type II (RCDII). Pathogenesis of active CD (ACD) has been shown to be related to gluten-specific immunity whereas the disease is no longer gluten driven in RCD. We therefore hypothesized that the immune response is differentially regulated by cytokines in ACD versus RCDII and investigated mucosal cytokine release after polyclonal stimulation of isolated mucosal lymphocytes. Secretion of theTH2cytokine IL-13 was significantly higher in lamina propria leukocytes (LPLs) isolated from RCDII patients as compared to LPL from ACD patients(P=0.05). In patients successfully treated with a gluten-free diet LPL-derived IL-13 production was also higher as compared to ACD patients(P=0.02). IL-13 secretion correlated with otherTH2as well asTH1cytokines but not with IL-10 secretion. Overall, the cytokine production pattern of LPL in RCDII showed more similarities with LPL isolated from GFD patients than from ACD patients. Our data suggest that different immunological processes are involved in RCDII and ACD with a potential role for IL-13.

Refractory coeliac disease a reality: views from Pakistan

2016 ◽  
Vol 47 (1) ◽  
pp. 51-53
Author(s):  
Rajesh M Mandhwani ◽  
Rajesh K Wadhwa ◽  
Syed Mudassir Laeeq ◽  
Nasir Hasan Luck ◽  
Mohammad Mubarak ◽  
...  
Keyword(s):  
Coeliac Disease ◽  
Villous Atrophy ◽  
Immunosuppressive Agents ◽  
Signs And Symptoms ◽  
Intraepithelial Lymphocytes ◽  
Response To Treatment ◽  
Gluten Free ◽  
Refractory Celiac Disease ◽  
Small Intestinal ◽  
Refractory Coeliac Disease

Refractory coeliac disease (RCD) is described as persistence or recurrence of signs and symptoms of malabsorption with small-intestinal villous atrophy despite being on a strict gluten-free diet (GFD) for more than 12 months. RCD is a diagnosis of exclusion. There are two types of RCD, based upon the immunohistochemical features (presence of intraepithelial lymphocytes), response to treatment and prognosis. The treatment of RCD includes GFD and immunosuppressive agents. We hereby present a case of refractory celiac disease type II in a young man who later went on to develop Addisonian crisis and did not survive.

Gluten-related immunogenic peptides in stool as means to monitor compliance with gluten-free diet in children with newly dia gnosed coeliac disease

2021 ◽  
Vol 75 (6) ◽  
pp. 519-523
Author(s):  
Radim Vyhnánek ◽  
Ziad Khaznadar ◽  
Roman Vyhnánek ◽  
Milan Paulík
Keyword(s):  
Coeliac Disease ◽  
Blood Sample ◽  
Stool Sample ◽  
Tissue Transglutaminase ◽  
Sandwich Elisa ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Newly Diagnosed ◽  
Strict Adherence ◽  
Immunogenic Peptides

Objectives and study: To compare the values of gluten-related immunogenic peptides (GIP) in stool and anti-tissue transglutaminase IgA antibodies (anti-tTG IgA) in blood in children newly diagnosed with coeliac disease (CD). Methods: All children (2–15 y) newly diagnosed with CD between May 2018 and May 2020 at our clinic who complied with the inclusion criteria were invited to join the prospective study. During workup for CD, a stool sample to measure GIP was taken together with a blood sample to measure anti-tTG IgA. All newly diagnosed children were invited 4 months later for a check-up. Children and their caregivers were asked about known non-compliance with the gluten-free diet (GFD), a blood sample was taken to measure the anti-tTG IgA, and a stool sample was collected to measure GIP. Blood was evaluated for anti-tTG IgA by ELISA, and the stool was tested by quantitative Sandwich ELISA designed to detect and quantify GIP using the G12 antibody. Values of GIP and anti-tTG IgA were compared in terms of their relation to the upper limit of normal (ULN) of the particular method. Results: 29 children (18 girls) were enrolled in the study. The values of GIP in stool at the time of diagnosis were above the ULN (0.15 µg/g) in all children. Average 4.21, median 3.29, standard deviation (SD) 3.7. After the four months, all but three (89.7%) had values of GIP in the reference range. Average 0.29, median 0.12, SD 0.73. Similarly, anti-tTG IgA values were above the ULN (9.9 U/mL) at the time of diagnosis in all children. Average 164, median 195, SD 49. Although the anti-tTG IgA levels were lower at check-up in all but one child, only 10 (34.5%) showed values within the normal range, with an average of 27.9, median 12.0, and SD 38.9. All children declared strict adherence to GFD. Discussion: Using the GIP concentration in stool, adherence to GFD in our cohort of children is very good, better than that described in literature. Conclusion: Measuring GIP in stool could prove a more sensitive indicator of adherence to GFD in the early months after the diagnosis of CD when anti-tTG IgA are still elevated above the ULN due to their well-described gradual decrease after GFD initiation.

scholarly journals Non-Responsive Coeliac Disease: A Comprehensive Review from the NHS England National Centre for Refractory Coeliac Disease

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 216 ◽  
Author(s):  
Hugo A. Penny ◽  
Elisabeth M. R. Baggus ◽  
Anupam Rej ◽  
John A. Snowden ◽  
David S. Sanders
Keyword(s):  
Coeliac Disease ◽  
Systematic Approach ◽  
Intestinal Inflammation ◽  
Gluten Free ◽  
Comprehensive Review ◽  
National Centre ◽  
Alternative Condition ◽  
Small Intestinal ◽  
Symptoms And Signs ◽  
Refractory Coeliac Disease

Coeliac disease is a common small intestinal enteropathy which manifests following ingestion of gluten in genetically susceptible individuals. Since gluten was identified as the driving factor in coeliac disease, the gluten-free diet (GFD) has remained the mainstay of treatment. While most individuals will display improvement in symptoms and signs of coeliac disease following institution of the GFD, up to 30% will continue to experience symptoms and/or have persisting intestinal inflammation. These individuals can be classified as having non-responsive coeliac disease (NRCD), which may be associated with dietary indiscretion, slow healing, refractory coeliac disease, and/or an alternative condition. The purpose of this review is to provide an overview of the causes of NRCD in adults, highlight a systematic approach to investigate these patients, and appraise the latest management aspects of this subset of coeliac disease.

scholarly journals Approach to patients with refractory coeliac disease

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2544 ◽  
Author(s):  
Ikram Nasr ◽  
Iman Nasr ◽  
Hannah Campling ◽  
Paul J. Ciclitira
Keyword(s):  
T Cell ◽  
Coeliac Disease ◽  
Cell Receptor ◽  
Management Approach ◽  
Pharmacological Management ◽  
Strict Adherence ◽  
Epithelial Lymphocyte ◽  
Refractory Coeliac Disease

Refractory coeliac disease (RCD) is a recognised complication, albeit very rare, of coeliac disease (CD). This condition is described when individuals with CD continue to experience enteropathy and subsequent or ongoing malabsorption despite strict adherence to a diet devoid of gluten for at least 12 months and when all other causes mimicking this condition are excluded. Depending on the T-cell morphology and T-cell receptor (TCR) clonality at the β/γ loci, RCD can be subdivided into type 1 (normal intra-epithelial lymphocyte morphology, polyclonal TCR population) and type 2 (aberrant IELs with clonal TCR). It is important to differentiate between the two types as type 1 has an 80% survival rate and is managed with strict nutritional and pharmacological management. RCD type 2 on the other hand has a 5-year mortality of 50% and can be complicated by ulcerative jejunitis or enteropathy-associated T-cell lymphoma (EATL). Management of RCD type 2 has challenged many experts, and different treatment approaches have been adopted with variable results. Some of these treatments include immunomodulation with azathioprine and steroids, methotrexate, cyclosporine, alemtuzumab (an anti CD-52 monoclonal antibody), and cladribine or fludarabine sometimes with autologous stem cell transplantation. In this article, we summarise the management approach to patients with RCD type 2.

scholarly journals Symposium 1: Joint BAPEN and British Society of Gastroenterology Symposium on ‘Coeliac disease: basics and controversies’ Coeliac disease: optimising the management of patients with persisting symptoms?

2009 ◽  
Vol 68 (3) ◽  
pp. 242-248 ◽  
Author(s):  
Kate E. Evans ◽  
David S. Sanders
Keyword(s):  
Coeliac Disease ◽  
Management Strategy ◽  
Villous Atrophy ◽  
Management Plan ◽  
Gluten Free Diet ◽  
British Society ◽  
Gluten Free ◽  
Review Of The Literature ◽  
Refractory Coeliac Disease ◽  
Investigation Strategy

The vast majority of patients with coeliac disease will derive benefit from a gluten-free diet. However, some patients will not improve on the gluten-free diet or they will have a relapse of their symptoms. The present review will focus on this group of patients. Definitions for non-responsive coeliac disease and refractory coeliac disease will be provided. The most common reason for recurrent symptoms is continued gluten exposure. Other causes of persisting symptoms are discussed, including alternative causes of villous atrophy or co-existent pathology. Current literature is reviewed, including an initial investigation strategy for patients with persisting symptoms. A pragmatic management plan is described that can be initiated by any clinician. Finally, the current optimal investigational pathway for patients with refractory (or suspected refractory) coeliac disease is discussed and the reported effects of a number of therapeutic options are summarised. The aim of the present article is to provide clinicians with an up-to-date review of the literature in this clinical field and allow them to determine the most appropriate management strategy.

scholarly journals PRESENT DATA IN THE DIAGNOSIS AND TREATMENT OF COELIAC DISEASE (2)

2017 ◽  
Vol 64 (1) ◽  
pp. 25-33
Author(s):  
Dan Olteanu ◽  
◽  
Alexandru Diaconescu ◽  
Radu Voiosu ◽  
Andrei Voiosu ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Coeliac Disease ◽  
Disease Incidence ◽  
Diagnostic Value ◽  
Gluten Free Diet ◽  
Intestinal Biopsy ◽  
Gluten Free ◽  
Refractory Celiac Disease ◽  
Small Intestinal Biopsy ◽  
Small Intestinal

Coeliac disease incidence rised during the last 50 years and represents a concern by diagnostic problems and costs. The recent data regarding etiology, pathogeny, comparative diagnostic value of serology and small intestinal biopsy are summarised. The new data about refractory celiac disease to gluten free diet and therapeutic perspectives are also presented (glutenases, larazotide acetate, genetic alteration of cereals, tissulary transglutaminase inhibitors etc).

scholarly journals Activated gut-homing CD8+ T cells for coeliac disease diagnosis on a gluten-free diet

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fernando Fernández-Bañares ◽  
Natalia López-Palacios ◽  
María Corzo ◽  
Beatriz Arau ◽  
Mercedes Rubio ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Coeliac Disease ◽  
Disease Diagnosis ◽  
T Cell Response ◽  
Gluten Free Diet ◽  
T Cell Subsets ◽  
Intestinal Damage ◽  
Gluten Free ◽  
Ifn Γ

Abstract Background The diagnosis of coeliac disease (CD) in individuals that have started a gluten-free diet (GFD) without an adequate previous diagnostic work-out is a challenge. Several immunological assays such as IFN-γ ELISPOT have been developed to avoid the need of prolonged gluten challenge to induce the intestinal damage. We aimed to evaluate the diagnostic accuracy of activated gut-homing CD8+ and TCRγδ+ T cells in blood after a 3-day gluten challenge and to compare it with the performance of IFN-γ ELISPOT in a HLA-DQ2.5 subsample. Methods A total of 22 CD patients and 48 non-CD subjects, all of them following a GFD, underwent a 3-day 10-g gluten challenge. The percentage of two T cell subsets (CD8+ CD103+ β7hi CD38+/total CD8+ and TCRγδ+ CD103+ β7hi CD38+/total TCRγδ+) in fresh peripheral blood drawn baseline and 6 days after the challenge was determined by flow cytometry. IFN-γ ELISPOT assays were also performed in HLA-DQ2.5 participants. ROC curve analysis was used to assess the diagnostic performance of the CD8+ T cell response and IFN-γ ELISPOT. Results Significant differences between the percentage of the two studied subsets of CD8+ and TCRγδ+ cells at days 0 and 6 were found only when considering CD patients (p < 10−3 vs. non-CD subjects). Measuring activated CD8+ T cells provided accurate CD diagnosis with 95% specificity and 97% sensitivity, offering similar results than IFN-γ ELISPOT. Conclusions The results provide a highly accurate blood test for CD diagnosis in patients on a GFD of easy implementation in daily clinical practice.

scholarly journals Present data in the diagnosis and treatment of coeliac disease (Part I)

2016 ◽  
Vol 63 (4) ◽  
pp. 272-279
Author(s):  
Dan Olteanu ◽  
◽  
Alexandru Diaconescu ◽  
Radu Voiosu ◽  
Andrei Voiosu ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Coeliac Disease ◽  
Disease Incidence ◽  
Diagnostic Value ◽  
Gluten Free Diet ◽  
Intestinal Biopsy ◽  
Gluten Free ◽  
Refractory Celiac Disease ◽  
Small Intestinal Biopsy ◽  
Small Intestinal

Coeliac disease incidence raised during the last 50 years and represents a concern by diagnostic problems and costs. The recent data regarding etiology, pathogeny, comparative diagnostic value of serology and small intestinal biopsy are summarised. New data about refractory celiac disease to gluten free diet and therapeutic perspectives are also presented (glutenases, larazotide acetate, genetic alteration of cereals, tissulary transglutaminase inhibitors etc).

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