T-cell repertoires in 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.

Download Full-text

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

Journal of Clinical Pathology ◽

10.1136/jclinpath-2018-205023 ◽

2018 ◽

Vol 71 (9) ◽

pp. 825-831 ◽

Cited By ~ 15

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.

Download Full-text

REFRACTORY COELIAC DISEASE: AN OPPORTUNITY TO PREVENT A T-CELL LYMPHOMA

The Science of Gluten-Free Foods and Beverages ◽

10.1094/9781891127670.002 ◽

2009 ◽

pp. 13-22

Author(s):

W. H. M. Verbeek

Keyword(s):

T Cell ◽

Coeliac Disease ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Refractory Coeliac Disease

Download Full-text

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

Journal of Clinical Pathology ◽

10.1136/jcp.2008.058404 ◽

2008 ◽

Vol 61 (11) ◽

pp. 1200-1202 ◽

Cited By ~ 3

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.

Download Full-text