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 Management of Patients with Refractory Coeliac Disease

2021 ◽  
Author(s):  
Paul J. Ciclitira ◽  
Alastair Forbes
Keyword(s):  
Small Intestine ◽  
High Risk ◽  
Coeliac Disease ◽  
Intraepithelial Lymphocytes ◽  
Gluten Free Diet ◽  
Immune Mediated ◽  
Ulcerative Jejunitis ◽  
Refractory Coeliac Disease

Coeliac disease (CD) is an immune-mediated disorder affecting the small intestine. The condition represents an intolerance to gluten. Removal of dietary gluten permits recovery, with a full recovery for the majority of affected subjects. A percentage of affected subjects who do not improve with a gluten-free diet are considered to have refractory coeliac disease (RCD). Refractory coeliac disease is subdivided into type 1, characterised by a polyclonal expansion of intraepithelial lymphocytes (IELs) that have a normal phenotype, and type 2 (RCD2) which exhibits IELs with a monoclonal phenotype. Subjects with RCD carry a high risk of complications, including ulcerative jejunitis and lymphoma affecting the small intestine, the latter termed enteropathy-associated T-cell lymphoma (EATL).

scholarly journals Clonal T cell receptor gene rearrangements in coeliac disease: implications for diagnosing refractory coeliac disease

2018 ◽  
Vol 71 (9) ◽  
pp. 825-831 ◽  
Author(s):  
Shafinaz Hussein ◽  
Tatyana Gindin ◽  
Stephen M Lagana ◽  
Carolina Arguelles-Grande ◽  
Suneeta Krishnareddy ◽  
...  
Keyword(s):  
T Cell ◽  
Coeliac Disease ◽  
T Cell Receptor ◽  
Rare Complication ◽  
Cell Receptor ◽  
High Morbidity ◽  
Gene Rearrangements ◽  
Pathological Feature ◽  
Significant Difference ◽  
Refractory Coeliac Disease

AimsRefractory coeliac disease type II (RCDII), a rare complication of coeliac disease (CD) associated with high morbidity, requires identification of a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs) for diagnosis. However, data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII are limited.MethodsWe analysed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active CD, 172 CD on gluten-free diet (GFD), 33 RCDI, and three RCDII patients and 14 patients without CD. TCR-GR patterns were divided into clonal, polyclonal and prominent clonal peaks (PCPs) and these patterns were correlated with clinical and pathological features.ResultsClonal TCR-GR products were detected in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with GFD. PCPs were observed in all disease phases (range 12%–33%). There was no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). A higher frequency of surface CD3(−) IELs was noted in cases with clonal TCR-GR, but the PCP pattern did not show associations with any clinical or pathological feature. Persistence of clonal or PCP pattern on repeat biopsy was seen for up to 2 years without evidence of RCDII.ConclusionsClonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.

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.

T-cell receptor antagonist modifies cytokine secretion profile of naive CD4+ T cells and their differentiation into type-1 and type-2 helper T cells

2005 ◽  
Vol 96 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Rumi Takato-Kaji ◽  
Mamoru Totsuka ◽  
Wataru Ise ◽  
Megumi Nishikawa ◽  
Satoshi Hachimura ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Receptor Antagonist ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Helper T Cells ◽  
Secretion Profile ◽  
Cytokine Secretion Profile

scholarly journals Diacylglycerol Kinase alpha in X Linked Lymphoproliferative Disease Type 1

2021 ◽  
Vol 22 (11) ◽  
pp. 5816
Author(s):  
Suresh Velnati ◽  
Sara Centonze ◽  
Federico Girivetto ◽  
Gianluca Baldanzi
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Adaptor Protein ◽  
Diacylglycerol Kinase ◽  
Cell Receptor ◽  
Lymphoproliferative Disease ◽  
Disease Type ◽  
T Cell Response ◽  
Receptor Signalling

Diacylglycerol kinases are intracellular enzymes that control the balance between the secondary messengers diacylglycerol and phosphatidic acid. DGKα and DGKζ are the prominent isoforms that restrain the intensity of T cell receptor signalling by metabolizing PLCγ generated diacylglycerol. Thus, their activity must be tightly controlled to grant cellular homeostasis and refine immune responses. DGKα is specifically inhibited by strong T cell activating signals to allow for full diacylglycerol signalling which mediates T cell response. In X-linked lymphoproliferative disease 1, deficiency of the adaptor protein SAP results in altered T cell receptor signalling, due in part to persistent DGKα activity. This activity constrains diacylglycerol levels, attenuating downstream pathways such as PKCθ and Ras/MAPK and decreasing T cell restimulation induced cell death. This is a form of apoptosis triggered by prolonged T cell activation that is indeed defective in CD8+ cells of X-linked lymphoproliferative disease type 1 patients. Accordingly, inhibition or downregulation of DGKα activity restores in vitro a correct diacylglycerol dependent signal transduction, cytokines production and restimulation induced apoptosis. In animal disease models, DGKα inhibitors limit CD8+ expansion and immune-mediated tissue damage, suggesting the possibility of using inhibitors of diacylglycerol kinase as a new therapeutic approach.

scholarly journals T-cell receptor repertoire variation may be associated with type 2 diabetes mellitus in humans

2016 ◽  
Vol 32 (3) ◽  
pp. 297-307 ◽  
Author(s):  
Joseph A. Frankl ◽  
Marie S. Thearle ◽  
Cindy Desmarais ◽  
Clifton Bogardus ◽  
Jonathan Krakoff
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire
Sign in / Sign up

Export Citation Format

Share Document