Evaluation of T cells in blood after a short gluten challenge for coeliac disease diagnosis

López-Palacios, Natalia; Pascual, Virginia; Castaño, Mercedes; Bodas, Andrés; Fernández-Prieto, Marta; Espino-Paisán, Laura; Martínez-Ojinaga, Eva; Salazar, Ma Isabel; Martínez-Curiel, Raquel; Rey, Enrique; Muñoz, Lourdes Estrada; Molero-Abraham, Magdalena; Reche, Pedro A.; Dieli-Crimi, Romina; Núñez, Concepción

doi:10.1016/j.dld.2018.04.014

Cited by 18 publications

(21 citation statements)

References 22 publications

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“…Therefore, we investigated the possible role of CX3CL1 and other IFN-γ-induced chemokines in the early phase of CD, by studying their changes after a gluten challenge. IFN-γ and IP-10 increased in the peripheral blood of CD patients six days after starting a 3-day gluten challenge [20,24]. In this work, we observed the parallel increase of CX3CL1, I-TAC and MIG.…”

Section: Discussionsupporting

confidence: 53%

“…We demonstrate that gluten-induced IFN-γ seems to be one of those stimuli. It should be noted that activated CD4, CD8 and γδ T cellswith gut-homing receptors are also observed in the blood of CD patients at day 6 of the 3-day gluten challenge [23,24,27]. Due to the chemotactic properties of the studied analytes, CX3CL1, coordinated with, at least, IP-10, I-TAC and MIG, would contribute to the recruitment of lymphocytes to the intestinal epithelium, which characterizes the early phase of CD.…”

Section: Discussionmentioning

confidence: 99%

“…Some participants were exposed to three days of gluten, according to previous publications, [23,24] following a protocol previously described [24]. Briefly, after at least one month on a GFD, individuals consumed approximately 10–14 g of gluten every day for three consecutive days.…”

Section: Methodsmentioning

confidence: 99%

“…Data of soluble CX3CL1, I-TAC and MIG in sera were analysed as previously described [24]. Briefly, a MIXED procedure in a 2 × 2 factorial design was used in the SAS software, with factors being the category group (CD and controls) as a fixed factor, the sampling time (day 0 and day 6) as a repeated measure, and the interaction between both of them.…”

Section: Methodsmentioning

confidence: 99%

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CX3CL1–CX3CR1 Axis: A New Player in Coeliac Disease Pathogenesis

et al. 2019

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Background: The CX3CL1–CX3CR1 axis has been related to numerous diseases. The aim of our study was to investigate its involvement in coeliac disease (CD) pathogenesis, particularly in the early phase of the disease. Methods: We collected peripheral blood from CD patients and controls, enrolled in a 3-day gluten challenge, to study soluble CX3CL1, I-TAC and MIG by Luminex, CX3CL1 and CX3CR1 gene expression by qPCR, and CX3CR1 protein expression in monocytes and CD8+, CD4+ and γδ+ T cells, by flow cytometry. We also analysed the expression of the CX3CL1 and CX3CR1 mRNA and protein in the duodenal biopsies of CD patients with active and treated disease, and in non-CD control individuals, by qPCR and immunohistochemistry. Results: After the gluten challenge, increased levels of CX3CL1, I-TAC and MIG proteins were observed in the peripheral blood of CD patients, with no changes in CX3CL1 mRNA, or CX3CR1 mRNA and protein. Regarding duodenal tissue, CX3CL1 was absent or barely present in the superficial and basal epithelium of CD patients, contrasting with the moderate to high levels present in controls. Conclusions: CX3CL1 seems to be involved in the appearance and progression of CD, and it appears to be a potential diagnostic biomarker. Its use as an alternative therapeutic target in CD deserves further research.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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CX3CL1–CX3CR1 Axis: A New Player in Coeliac Disease Pathogenesis

et al. 2019

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“…To develop a comprehensive mass cytometry workflow for monitoring GI trafficking blood cells in CeD patients, we first identified the major immune cell lineages and their subsets, including T cells, B cells, monocytes, dendritic cells, and NK cells. The importance of integrin expressing lymphocytes, chemokine receptors, markers of T cell activation and myeloid differentiation markers have also been implicated in the pathophysiology of CeD (Ben‐Horin et al, 2006; Jabri & Sollid, 2017; López‐Palacios et al, 2018; Sabatino et al, 2001; Tye‐Din et al, 2018) and thus were included in the panel. Of the markers selected, included were integrins β7, α4, and αE, chemokine receptors CCR4 and CCR9, T cell activation markers PD‐1, CD38, HLA‐DR, and CTLA‐4 and markers of myeloid differentiation PD‐L1, CD303, CD304, CD1c, and CTLA‐4.…”

Section: Resultsmentioning

confidence: 99%

Development and validation of a high‐parameter mass cytometry workflow to decipher immunomodulatory changes in celiac disease

Estevam

Krutzik

Tuig

et al. 2021

Cytometry Part B Clinical

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The advent of time‐of‐flight mass cytometry (CyTOF) has enabled high dimensional and unbiased examination of the immune system to simultaneous interrogate a multitude of parameters and gain a better understanding of immunologic data from clinical trial samples. Here we describe the development and validation of a 33‐marker mass cytometry workflow for measuring gastrointestinal (GI) trafficking peripheral blood mononuclear cells (PBMCs) in patients with celiac disease (CeD). This panel builds upon identification of well‐characterized immune cells and expands to include markers modulated in response to gluten challenge in patients with CeD. The CeD panel was optimized and validated according to accepted industry practice for validation of flow cytometry assays and builds upon established sample processing workflows for mass cytometry studies. Several critical parameters were evaluated during the assay development phase of this study including optimization of the sample processing steps, antibody specificity, and ensuring the panel as a whole performed to expectation. The panel was then validated using a fit‐for‐purpose approach tailored to the intended use of the data in the clinical trial. Validation included assessment of analytical parameters essential to understanding the reliability and robustness of the CeD panel such as intra‐assay precision, inter‐assay precision, inter‐operator precision and sample processing stability. Together, this validated mass cytometry workstream provides robust and reproducible high‐dimensional analysis of human peripheral blood immune cells to characterize patient samples from clinical trials.

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Pathogenic T Cells in Celiac Disease Change Phenotype on Gluten Challenge: Implications for T‐Cell‐Directed Therapies

et al. 2021

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Gluten-specific CD4 + T cells being drivers of celiac disease (CeD) are obvious targets for immunotherapy. Little is known about how cell markers harnessed for T-cell-directed therapy can change with time and upon activation in CeD and other autoimmune conditions. In-depth characterization of gluten-specific CD4 + T cells and CeD-associated (CD38 + and CD103 + ) CD8 + and 𝜸𝜹 + T cells in blood of treated CeD patients undergoing a 3 day gluten challenge is reported. The phenotypic profile of gluten-specific cells changes profoundly with gluten exposure and the cells adopt the profile of gluten-specific cells in untreated disease (CD147 + , CD70 + , programmed cell death protein 1 (PD-1) + , inducible T-cell costimulator (ICOS) + , CD28 + , CD95 + , CD38 + , and CD161 + ), yet with some markers being unique for day 6 cells (C-X-C chemokine receptor type 6 (CXCR6), CD132, and CD147) and with integrin 𝜶4𝜷7, C-C motif chemokine receptor 9 (CCR9), and CXCR3 being expressed stably at baseline and day 6. Among gluten-specific CD4 + T cells, 52% are CXCR5 + at baseline, perhaps indicative of germinal-center reactions, while on day 6 all are CXCR5 − . Strikingly, the phenotypic profile of gluten-specific CD4 + T cells on day 6 largely overlaps with that of CeD-associated (CD38 + and CD103 + ) CD8 + and 𝜸𝜹 + T cells. The antigen-induced shift in phenotype of CD4 + T cells being shared with other disease-associated T cells is relevant for development of T-cell-directed therapies.

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Evaluation of T cells in blood after a short gluten challenge for coeliac disease diagnosis

Abstract: A short three-day gluten challenge elicits the activation of CD103 β7 CD8 T cells in CD. These cells can be detected by flow cytometry in peripheral blood, opening new possibilities for CD diagnosis in individuals on a GFD.

Cited by 18 publications

References 22 publications

CX3CL1–CX3CR1 Axis: A New Player in Coeliac Disease Pathogenesis

CX3CL1–CX3CR1 Axis: A New Player in Coeliac Disease Pathogenesis

Development and validation of a high‐parameter mass cytometry workflow to decipher immunomodulatory changes in celiac disease

Pathogenic T Cells in Celiac Disease Change Phenotype on Gluten Challenge: Implications for T‐Cell‐Directed Therapies

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