TCRβ Clonality Improves Diagnostic Yield of TCRγ Clonality in Refractory Celiac Disease

Perfetti, Vittorio; Brunetti, Laura; Biagi, Federico; Ciccocioppo, Rachele

doi:10.1097/mcg.0b013e31823eff20

Cited by 23 publications

(12 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 5–8 Strategies to diagnose RCD type II include immunohistochemistry revealing a loss of CD8 in intraepithelial lymphocytes (IELs) in combination with evidence for clonal expansion of IELs, as uncovered by T-cell receptor β (TCRβ) or TCRγ-PCR in duodenal samples. 9 10 Alternative diagnostic procedures include flow cytometric immunophenotyping of isolated IELs from duodenal mucosa. 11 …”

Section: Introductionmentioning

confidence: 99%

T-cell repertoires in refractory coeliac disease

Ritter

Zimmermann

Jöhrens

et al. 2017

Gut

View full text Add to dashboard Cite

ObjectiveRefractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis.DesignDNA extracted from duodenal mucosa specimens of controls (n=9), active coeliacs (n=10), coeliacs on a gluten-free diet (n=9), RCD type I (n=8), RCD type II (n=8) and unclassified Marsh I cases (n=3) collected from 2002 to 2013 was examined by TCRβ-complementarity-determining regions 3 (CDR3) multiplex PCR followed by HTS of the amplicons.ResultsOn average, 106 sequence reads per sample were generated consisting of up to 900 individual TCRβ rearrangements. In RCD type II, the most frequent clonotypes (ie, sequence reads with identical CDR3) represent in average 42.6% of all TCRβ rearrangements, which was significantly higher than in controls (6.8%; p<0.01) or RCD type I (6.7%; p<0.01). Repeat endoscopies in individual patients revealed stability of clonotypes for up to several years without clinical symptoms of EATL. Dominant clonotypes identified in individual patients with RCD type II were unique and not related between patients. CD-associated, gliadin-dependent CDR3 motifs were only detectable at low frequencies.ConclusionsTCRβ-HTS analysis unravels the TCR in CD and allows detailed analysis of individual TCRβ rearrangements. Dominant TCRβ sequences identified in patients with RCD type II are unique and not homologous to known gliadin-specific TCR sequences, supporting the assumption that these clonal T-cells expand independent of gluten stimulation.

show abstract

Section: Introductionmentioning

confidence: 99%

T-cell repertoires in refractory coeliac disease

Ritter

Zimmermann

Jöhrens

et al. 2017

Gut

View full text Add to dashboard Cite

show abstract

“…Analysis of the delta chain rearrangement may be useful for diagnosis of RCDII in patients presenting oligoclonal rearrangement of the gamma chain [22]. Others have suggested interest of detecting of the beta chain of the TCR [31]. Finally, specificity of the PCR product needs to be attested by formation of homoduplexes [22].…”

Section: Refractory Coeliac Diseasementioning

confidence: 96%

Complications of coeliac disease

Malamut¹,

Cellier²

2015

Best Practice & Research Clinical Gastroenterology

View full text Add to dashboard Cite

“…Analysis of the delta chain rearrangement may be useful in RCDII patients presenting oligoclonal rearrangement of the gamma chain [7]. Interest of detecting the beta chain of the TCR has also been suggested [20]. Nevertheless, evidence that abnormal IELs originate from immature T cells tempers interest of studying beta rearrangement which occurs later in the ontogeny.…”

Section: Diagnosismentioning

confidence: 97%