12 results on '"Koning, F."'
Search Results
2. An immunodominant DQ8 restricted gliadin peptide activates small intestinal immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative coeliac patients. (Small Intestine)
- Author
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Mazzarella, G., Maglio, M., Paparo, F., Nardone, G., Stefanile, R., Greco, L., Wal, Y. van de, Kooy, Y., Koning, F., Auricchio, S., and Troncone, R.
- Subjects
Celiac disease -- Research -- Health aspects ,HLA class II antigens -- Health aspects -- Research ,Health - Abstract
Background: Studies on intestinal T cell clones from the mucosa of patients with coeliac disease have led to the identification of immunogenic gliadin epitopes. One is HLA-DQ8 restricted, its recognition [...]
- Published
- 2003
3. A novel and sensitive method for the detection of T cell stimulatory epitopes of α/β- and γ-gliadin
- Author
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Spaenij-Dekking, E H A, Kooy-Winkelaar, E M C, Nieuwenhuizen, W F, Drijfhout, J W, and Koning, F
- Published
- 2004
4. Coeliac disease: it takes three to tango!
- Author
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VAN DE WAL, Y, KOOY, Y, VAN VEELEN, P, VADER, W, KONING, F, and PEÑA, S
- Published
- 2000
5. Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for coeliac disease
- Author
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Mitea, C, primary, Havenaar, R, additional, Drijfhout, J W., additional, Edens, L, additional, Dekking, L, additional, and Koning, F, additional
- Published
- 2007
- Full Text
- View/download PDF
6. A novel and sensitive method for the detection of T cell stimulatory epitopes of &alph;/β- and γ-gliadin.
- Author
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Spaenij-Dekking, E. H. A., Kooy-Winkelaar, E. M. C., Nieuwenhuizen, W. F., Drijfhout, J. W., and Koning, F.
- Subjects
CELIAC disease ,T cells ,PEPTIDES ,EPITOPES ,PROTEINS ,MONOCLONAL antibodies - Abstract
Background: It is now generally accepted that coeliac disease (CD) is caused by inflammatory T cell responses to gluten peptides bound to HLA-DQ2 or -DQ8 molecules. There is overwhelming evidence that CD patients can mount T cell responses to peptides found in both α-gliadin and γ-gliadin molecules. Assays that would detect the presence or absence of such peptides in food would thus be accurate indicators of safety for consumption by CD patients. Aims: The development of a sensitive method to detect T cell stimulatory epitopes of α-gliadin and γ-gliadin molecules in food products. Methods: Monoclonal antibodies (mAb) were raised against peptides encoding the T cell stimulatory epitopes of α-gliadin (amino acids (aa) 59-71) and aa γ-gliadin (aa 142-153 and aa 147-159). These mAb competition assays were developed that quantitatively detect T cell stimulatory epitopes present on both intact proteins and peptides of sizes recognisable by CD4
+ T cells. Results: With the mAb based competition assays, T cell epitopes were detected in pepsin/trypsin digests of wheat proteins and ethanol extracts of various food products, with detection levels lower than those reached with gluten specific T cells. Moreover, the presence of T cell stimulatory epitopes was also detected in preparations of barley, rye, and triticale, other cereals known to be toxic for CD patients. Conclusions: A new antibody based method has been developed, detecting the presence of T cell stimulatory gluten peptides. This can be used to further ensure the safety of food consumed by CD patients. [ABSTRACT FROM AUTHOR]- Published
- 2004
- Full Text
- View/download PDF
7. Lack of relationship of AT1001 to zonulin and prehaptoglobin-2: clinical implications.
- Author
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Sollid LM and Koning F
- Subjects
- Biomarkers, Haptoglobins, Humans, Oligopeptides, Permeability, Protein Precursors
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2021
- Full Text
- View/download PDF
8. High-dimensional cytometric analysis of colorectal cancer reveals novel mediators of antitumour immunity.
- Author
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de Vries NL, van Unen V, Ijsselsteijn ME, Abdelaal T, van der Breggen R, Farina Sarasqueta A, Mahfouz A, Peeters KCMJ, Höllt T, Lelieveldt BPF, Koning F, and de Miranda NFCC
- Subjects
- Antigens, CD metabolism, CD8 Antigens metabolism, Case-Control Studies, Colonic Neoplasms metabolism, Flow Cytometry, Humans, Integrin alpha Chains metabolism, Lymphocyte Count, Lymphocytes, Tumor-Infiltrating, Colonic Neoplasms immunology, Colonic Neoplasms pathology
- Abstract
Objective: A comprehensive understanding of anticancer immune responses is paramount for the optimal application and development of cancer immunotherapies. We unravelled local and systemic immune profiles in patients with colorectal cancer (CRC) by high-dimensional analysis to provide an unbiased characterisation of the immune contexture of CRC., Design: Thirty-six immune cell markers were simultaneously assessed at the single-cell level by mass cytometry in 35 CRC tissues, 26 tumour-associated lymph nodes, 17 colorectal healthy mucosa and 19 peripheral blood samples from 31 patients with CRC. Additionally, functional, transcriptional and spatial analyses of tumour-infiltrating lymphocytes were performed by flow cytometry, single-cell RNA-sequencing and multispectral immunofluorescence., Results: We discovered that a previously unappreciated innate lymphocyte population (Lin
- CD7+ CD127- CD56+ CD45RO+ ) was enriched in CRC tissues and displayed cytotoxic activity. This subset demonstrated a tissue-resident (CD103+ CD69+ ) phenotype and was most abundant in immunogenic mismatch repair (MMR)-deficient CRCs. Their presence in tumours was correlated with the infiltration of tumour-resident cytotoxic, helper and γδ T cells with highly similar activated (HLA-DR+ CD38+ PD-1+ ) phenotypes. Remarkably, activated γδ T cells were almost exclusively found in MMR-deficient cancers. Non-activated counterparts of tumour-resident cytotoxic and γδ T cells were present in CRC and healthy mucosa tissues, but not in lymph nodes, with the exception of tumour-positive lymph nodes., Conclusion: This work provides a blueprint for the understanding of the heterogeneous and intricate immune landscape of CRC, including the identification of previously unappreciated immune cell subsets. The concomitant presence of tumour-resident innate and adaptive immune cell populations suggests a multitargeted exploitation of their antitumour properties in a therapeutic setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2020
- Full Text
- View/download PDF
9. The composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment is altered in coeliac disease.
- Author
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Schmitz F, Kooy-Winkelaar Y, Wiekmeijer AS, Brugman MH, Mearin ML, Mulder C, Chuva de Sousa Lopes S, Mummery CL, Staal FJ, van Bergen J, and Koning F
- Subjects
- Cell Differentiation immunology, Cell Line, Cytokines immunology, Humans, Interleukin-7 Receptor alpha Subunit analysis, RNA Polymerase I, CD3 Complex analysis, Celiac Disease immunology, Celiac Disease pathology, Duodenum pathology, Intestinal Mucosa immunology, Intestinal Mucosa pathology, Intracellular Signaling Peptides and Proteins analysis, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets pathology
- Abstract
Objective: Coeliac disease (CD), a gluten-induced enteropathy, alters the composition and function of duodenal intraepithelial T cells. The intestine also harbours four types of CD3-negative intraepithelial lymphocytes (IELs) with largely unknown function: CD56(-)CD127(-), CD56(-)CD127(+), CD56(+)CD127(-) and CD56(+)CD127(+). Here we aimed to gain insight into the potential function of these innate IELs in health and disease., Design: We determined the phenotypes, relative abundance and differentiation potential of these innate IEL subsets in duodenal biopsies from controls and patients with CD or patients with refractory CD type II (RCDII)., Results: Hierarchical clustering analysis of the expression of 15 natural killer and T cell surface markers showed that innate IELs differed markedly from innate peripheral blood lymphocytes and divided innate IEL subsets into two main branches: a CD127(-) branch expressing high levels of interleukin (IL) 2/15Rβ but no IL-21R, and a CD127(+) branch with the opposite phenotype. While CD was characterised by the contraction of all four innate IEL subsets, a selective expansion of CD56(-)CD127(-) and CD56(-)CD127(+) innate IEL was detected in RCDII. In vitro, in the presence of IL-15, CD56(-)CD127(-) IEL from controls and patients with CD, but not from patients with RCDII, differentiated into functional natural killer and T cells, the latter largely dependent on notch-signalling. Furthermore, compared with non-coeliac controls, CD56(-)CD127(-) IEL from patients with CD expressed more intracellular CD3ε and CD3γ and gave more pronounced T cell differentiation., Conclusions: Thus, we demonstrate previously unappreciated diversity and plasticity of the innate IEL compartment and its loss of differentiation potential in patients with RCDII., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
- Published
- 2016
- Full Text
- View/download PDF
10. Identification of a potential physiological precursor of aberrant cells in refractory coeliac disease type II.
- Author
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Schmitz F, Tjon JM, Lai Y, Thompson A, Kooy-Winkelaar Y, Lemmers RJ, Verspaget HW, Mearin ML, Staal FJ, Schreurs MW, Cupedo T, Langerak AW, Mulder CJ, van Bergen J, and Koning F
- Subjects
- Antigens, CD immunology, Biomarkers analysis, Biopsy, Cell Line, Cells, Cultured, Flow Cytometry, Humans, Interleukin-15 immunology, Killer Cells, Natural immunology, Killer Cells, Natural pathology, Phenotype, Real-Time Polymerase Chain Reaction, Receptors, Antigen, T-Cell immunology, Tissue Array Analysis, Celiac Disease immunology, Celiac Disease pathology, Duodenum immunology, Duodenum pathology, Intestinal Mucosa immunology, Intestinal Mucosa pathology, Lymphocytes immunology, Lymphocytes pathology
- Abstract
Objective: Refractory coeliac disease type II (RCDII) is a severe complication of coeliac disease (CD) characterised by aberrant intraepithelial lymphocytes (IELs) of unknown origin that display an atypical CD3(-)CD7(+)icCD3(+) phenotype. In approximately 40% of patients with RCDII these lymphocytes develop into an invasive lymphoma. In the current study we aimed to identify the physiological counterpart of these cells., Design: RCDII cell lines were compared with T-cell receptor positive (TCR(+)) IEL (T-IEL) lines by microarray analysis, real-time quantitative PCR and flow cytometry. This information was used to identify cells with an RCDII-associated phenotype in duodenal biopsies from non-refractory individuals by multicolour flow cytometry., Results: RCDII lines were transcriptionally distinct from T-IEL lines and expressed higher levels of multiple natural killer (NK) cell receptors. In addition to the CD3(-)CD7(+)icCD3(+) phenotype, the RCDII lines were distinguishable from other lymphocyte subsets by the absence of CD56, CD127 and CD34. Cells matching this surface lineage-negative (Lin(-)) CD7(+)CD127(-)CD34(-) phenotype expressed a functional interleukin-15 (IL-15) receptor and constituted a significant proportion of IELs in duodenal specimens of patients without CD, particularly children, and were also found in the thymus. In patients without CD, the Lin(-)CD7(+)CD127(-)CD34(-) subset was one of four subsets within the CD3(-)CD7(+)icCD3(+) population that could be distinguished on the basis of differential expression of CD56 and/or CD127., Conclusion: Our studies indicate that the CD3(-)CD7(+)icCD3(+) population is heterogeneous and reveal the existence of a Lin(-) subset that is distinct from T, B, NK and lymphoid tissue inducer cells. We speculate that this IL-15 responsive population represents the physiological counterpart of aberrant cells expanded in RCDII and transformed in RCDII-associated lymphoma.
- Published
- 2013
- Full Text
- View/download PDF
11. Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study.
- Author
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Duijvestein M, Vos AC, Roelofs H, Wildenberg ME, Wendrich BB, Verspaget HW, Kooy-Winkelaar EM, Koning F, Zwaginga JJ, Fidder HH, Verhaar AP, Fibbe WE, van den Brink GR, and Hommes DW
- Subjects
- Adult, Cell Differentiation, Cell Proliferation, Cells, Cultured, Colonoscopy, Crohn Disease immunology, Crohn Disease pathology, Cytokines biosynthesis, Dose-Response Relationship, Immunologic, Epidemiologic Methods, Female, Humans, Immune Tolerance, Immunity, Mucosal, Male, Mesenchymal Stem Cell Transplantation adverse effects, Stromal Cells transplantation, T-Lymphocyte Subsets immunology, Young Adult, Crohn Disease therapy, Mesenchymal Stem Cell Transplantation methods
- Abstract
Background and Aim: Mesenchymal stromal cells (MSCs) are pluripotent cells that have immunosuppressive effects both in vitro and in experimental colitis. Promising results of MSC therapy have been obtained in patients with severe graft versus host disease of the gut. Our objective was to determine the safety and feasibility of autologous bone marrow derived MSC therapy in patients with refractory Crohn's disease., Patients and Intervention: 10 adult patients with refractory Crohn's disease (eight females and two males) underwent bone marrow aspiration under local anaesthesia. Bone marrow MSCs were isolated and expanded ex vivo. MSCs were tested for phenotype and functionality in vitro. 9 patients received two doses of 1-2×10(6) cells/kg body weight, intravenously, 7 days apart. During follow-up, possible side effects and changes in patients' Crohn's disease activity index (CDAI) scores were monitored. Colonoscopies were performed at weeks 0 and 6, and mucosal inflammation was assessed by using the Crohn's disease endoscopic index of severity., Results: MSCs isolated from patients with Crohn's disease showed similar morphology, phenotype and growth potential compared to MSCs from healthy donors. Importantly, immunomodulatory capacity was intact, as Crohn's disease MSCs significantly reduced peripheral blood mononuclear cell proliferation in vitro. MSC infusion was without side effects, besides a mild allergic reaction probably due to the cryopreservant DMSO in one patient. Baseline median CDAI was 326 (224-378). Three patients showed clinical response (CDAI decrease ≥70 from baseline) 6 weeks post-treatment; conversely three patients required surgery due to disease worsening., Conclusions: Administration of autologous bone marrow derived MSCs appears safe and feasible in the treatment of refractory Crohn's disease. No serious adverse events were detected during bone marrow harvesting and administration.
- Published
- 2010
- Full Text
- View/download PDF
12. A novel and sensitive method for the detection of T cell stimulatory epitopes of alpha/beta- and gamma-gliadin.
- Author
-
Spaenij-Dekking EH, Kooy-Winkelaar EM, Nieuwenhuizen WF, Drijfhout JW, and Koning F
- Subjects
- Animals, Antibodies, Monoclonal immunology, Binding, Competitive, Cell Division immunology, Edible Grain immunology, Enzyme-Linked Immunosorbent Assay methods, Epitopes, T-Lymphocyte immunology, Food, Food Analysis methods, Humans, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Peptide Fragments immunology, T-Lymphocytes immunology, Epitopes, T-Lymphocyte analysis, Gliadin immunology
- Abstract
Background: It is now generally accepted that coeliac disease (CD) is caused by inflammatory T cell responses to gluten peptides bound to HLA-DQ2 or -DQ8 molecules. There is overwhelming evidence that CD patients can mount T cell responses to peptides found in both alpha-gliadin and gamma-gliadin molecules. Assays that would detect the presence or absence of such peptides in food would thus be accurate indicators of safety for consumption by CD patients., Aims: The development of a sensitive method to detect T cell stimulatory epitopes of alpha-gliadin and gamma-gliadin molecules in food products., Methods: Monoclonal antibodies (mAb) were raised against peptides encoding the T cell stimulatory epitopes of alpha-gliadin (amino acids (aa) 59-71) and aa gamma-gliadin (aa 142-153 and aa 147-159). These mAb competition assays were developed that quantitatively detect T cell stimulatory epitopes present on both intact proteins and peptides of sizes recognisable by CD4(+) T cells., Results: With the mAb based competition assays, T cell epitopes were detected in pepsin/trypsin digests of wheat proteins and ethanol extracts of various food products, with detection levels lower than those reached with gluten specific T cells. Moreover, the presence of T cell stimulatory epitopes was also detected in preparations of barley, rye, and triticale, other cereals known to be toxic for CD patients., Conclusions: A new antibody based method has been developed, detecting the presence of T cell stimulatory gluten peptides. This can be used to further ensure the safety of food consumed by CD patients.
- Published
- 2004
- Full Text
- View/download PDF
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