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4. Enduring clinical remission in refractory celiac disease type II with tofacitinib: an open-label clinical study

Author

Dieckman, Tessa, primary, Schumann, Michael, additional, Beaumont, Hanneke, additional, Bontkes, Hetty J., additional, Koning, Frits, additional, Bouma, Gerd, additional, Byrnes, Valerie, additional, McCarthy, Jane, additional, Neefjes-Borst, Andra, additional, Loddenkemper, Christoph, additional, Weegh, Marlous op de, additional, and Lundin, K.E.A., additional

Published
2024
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6. Single-Cell Analysis of Refractory Celiac Disease Demonstrates Inter- and Intra-Patient Aberrant Cell Heterogeneity

Author

Dieckman, Tessa (author), Schreurs, Mette (author), Mahfouz, A.M.E.T.A. (author), Kooy-Winkelaar, Yvonne (author), Neefjes-Borst, Andra (author), Bouma, Gerd (author), Koning, Frits (author), Dieckman, Tessa (author), Schreurs, Mette (author), Mahfouz, A.M.E.T.A. (author), Kooy-Winkelaar, Yvonne (author), Neefjes-Borst, Andra (author), Bouma, Gerd (author), and Koning, Frits (author)

Abstract

Background & Aims: Refractory celiac disease type II (RCDII) is a rare indolent lymphoma in the small intestine characterized by a clonally expanded intraepithelial intracellular CD3+surfaceCD3-CD7+CD56- aberrant cell population. However, RCDII pathogenesis is ill-defined. Here, we aimed at single-cell characterization of the innate and adaptive immune system in RCDII. Methods: Paired small intestinal and blood samples from 12 RCDII patients and 6 healthy controls were assessed by single-cell mass cytometry with a 39–cell surface marker antibody panel, designed to capture heterogeneity of the innate and adaptive immune system. A second single-cell mass cytometry panel that included transcription factors and immune checkpoints was used for analysis of paired samples from 5 RCDII patients. Single-cell RNA sequencing analysis was performed on duodenal samples from 2 RCDII patients. Finally, we developed a 40-marker imaging mass cytometry antibody panel to evaluate cell–cell interactions in duodenal biopsy specimens of RCDII patients. Results: We provide evidence for intertumoral and intratumoral cell heterogeneity within the duodenal and peripheral aberrant cell population present in RCDII. Phenotypic discrepancy was observed between peripheral and duodenal aberrant cells. In addition, we observed that part of the aberrant cell population proliferated and observed co-localization of aberrant cells with CD163+ antigen-presenting cells (APCs) in situ. In addition, we observed phenotypic discrepancy between peripheral and duodenal aberrant cells. Conclusions: Novel high-dimensional single-cell technologies show substantial intertumoral and intratumoral heterogeneity in the aberrant cell population in RCDII. This may underlie variability in refractory disease status between patients and responsiveness to therapy, pointing to the need for personalized therapy in RCDII based on patient-specific immune profiles., Pattern Recognition and Bioinformatics

Published
2022
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8. ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation

Author

Ilaria Russo, Andra Neefjes-Borst, Kamran Ghaffarzadehgan, Vincenzo Villanacci, Anna Bozzola, Matt W Johnson, Azita Ganji, Mohammad H. Derakhshan, Alessandra Mandolesi, Alexandra Ciobanu, Angelo Sidoni, Arzu Ensari, Geoffrey Holmes, Marie E. Robert, Marilena Fiorino, Michael N. Marsh, Stefano Ferrero, James J. Going, Masoud Sotoudeh, David Aldulaimi, Kamran Rostami, Hamid Mohaghegh, Mihai Danciu, Carlo Catassi, Antonio Carroccio, Chris J. J. Mulder, Brigitte Bancel, Amitabh Srivastava, Calvin Heal, Gabrio Bassotti, Carolina Ciacci, Sauid Ishaq, Luca Elli, Mohammad Reza Zali, Mohammad Rostami-Nejad, Adrian C Bateman, Umberto Volta, Roxana Maxim, Michelangelo Fiorentino, Gabriel Becheanu, Sherly Mathews, Rostami, Kamran, Marsh, Michael N, Johnson, Matt W, Mohaghegh, Hamid, Heal, Calvin, Holmes, Geoffrey, Ensari, Arzu, Aldulaimi, David, Bancel, Brigitte, Bassotti, Gabrio, Bateman, Adrian, Becheanu, Gabriel, Bozzola, Anna, Carroccio, Antonio, Catassi, Carlo, Ciacci, Carolina, Ciobanu, Alexandra, Danciu, Mihai, Derakhshan, Mohammad H, Elli, Luca, Ferrero, Stefano, Fiorentino, Michelangelo, Fiorino, Marilena, Ganji, Azita, Ghaffarzadehgan, Kamran, Going, James J, Ishaq, Sauid, Mandolesi, Alessandra, Mathews, Sherly, Maxim, Roxana, Mulder, Chris J, Neefjes-borst, Andra, Robert, Marie, Russo, Ilaria, Rostami-nejad, Mohammad, Sidoni, Angelo, Sotoudeh, Masoud, Villanacci, Vincenzo, Volta, Umberto, Zali, Mohammad R, Srivastava, Amitabh, Gastroenterology and hepatology, AGEM - Re-generation and cancer of the digestive system, AGEM - Endocrinology, metabolism and nutrition, AGEM - Digestive immunity, Pathology, Other Research, and Rostami K, Marsh MN, Johnson MW, Mohaghegh H, Heal C, Holmes G, Ensari A, Aldulaimi D, Bancel B, Bassotti G, Bateman A, Becheanu G, Bozzola A, Carroccio A, Catassi C, Ciacci C, Ciobanu A, Danciu M, Derakhshan MH, Elli L, Ferrero S, Fiorentino M, Fiorino M, Ganji A, Ghaffarzadehgan K, Going JJ, Ishaq S, Mandolesi A, Mathews S, Maxim R, Mulder CJ, Neefjes-Borst A, Robert M, Russo I, Rostami-Nejad M, Sidoni A, Sotoudeh M, Villanacci V, Volta U, Zali MR, Srivastava A.

Subjects
Male, Pathology, Settore MED/09 - Medicina Interna, ROC-curve analysi, Biopsy, Coeliac disease, Serology, 0302 clinical medicine, intraepithelial lymphocytes, Diagnosis, 80 and over, ROC-curve analysis, coeliac disease, Lymphocytes, Intestinal Mucosa, Child, medicine.diagnostic_test, Area under the curve, Gastroenterology, hemic and immune systems, Middle Aged, Prognosis, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, medicine.symptom, tissues, Adult, medicine.medical_specialty, Adolescent, chemical and pharmacologic phenomena, Biology, digestive system, Lesion, 03 medical and health sciences, medicine, Humans, Lymphocyte Count, Preschool, Aged, Receiver operating characteristic, Infant, Histology, medicine.disease, Newborn, Aged, 80 and over, Case-Control Studies, Celiac Disease, Child, Preschool, Diagnosis, Differential, Infant, Newborn, ROC Curve, Differential, Intraepithelial lymphocyte
Abstract

ObjectivesCounting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive ‘normal’ IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens.DesignThe study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected.ResultsThe mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2–88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion.ConclusionOur ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose–response by IEL to environmental (gluten) antigenic influence.

Published
2017
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9. Inflammatory Bowel Disease in a Patient Returning from Colombia: Association with Dipeptidyl Peptidase 4 Inhibitor?

Author

Bayoumy AB, Masclee GMC, de Boer NKH, Neefjes-Borst A, and Stenvers DJ

Abstract

Introduction: Recent-onset colitis poses a diagnostic challenge, necessitating a thorough evaluation to identify potential infectious and non-infectious etiologies. We considered inflammatory bowel disease (IBD) secondary to dipeptidyl peptidase 4 (DPP-4) inhibitor-induced colitis., Case Presentation: This case report details the presentation and management of a patient with persistent dysentery, refractory to conventional treatments, ultimately attributed to IBD possibly secondary to long-term DPP-4 inhibitor use. Following an episode of suspected amebiasis, the patient experienced prolonged bloody diarrhea with an endoscopic image compatible with ulcerative colitis. Extensive infectious diagnostics were negative. Ultimately, the cessation of sitagliptin therapy resulted in rapid symptom resolution and normalization of eosinophilia, as well as endoscopic improvement. However, after a few weeks, the patient was readmitted with diarrhea after continued cessation of sitagliptin., Conclusion: This case underscores the importance of considering IBD secondary to DPP-4 inhibitor use in the evaluation of patients with recent-onset IBD. Further research is needed to elucidate the pathophysiological mechanisms underlying the relationship between DPP-4 inhibitors and IBD., Competing Interests: The authors have no conflicts of interest to declare., (© 2025 The Author(s). Published by S. Karger AG, Basel.)

Published
2025
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