Search

Your search keyword '"Karim Kreft"' showing total 3 results
Start Over Author "Karim Kreft"
3 results on '"Karim Kreft"'

1. Algorithmic Identification of Multiple Sclerosis in the SAIL databank

Author

Rod Middleton, Richard Nicholas, Emma Tallantyre, James Witts, Ruth Ann Marrie, Elaine Craig, Sarah Knowles, Owen Pearson, Katherine Harding, Karim Kreft, Jonathon Hawken, Gillian Ingram, Bethan Morgan, and Neil Robertson

Subjects
Demography. Population. Vital events, HB848-3697
Abstract

Background Multiple Sclerosis (MS) is a challenging disease to identify within large repositories of healthcare data. Diagnosis can be protracted requiring many modalities that may not form part of the repository data collection. Accurate case finding would have multiple applications for studying epidemiology. Aim Develop a case finding algorithm within the Secure Anonymised Information Linkage (SAIL) Databank that can reliably elicit Multiple Sclerosis. Method Utilising a cross sectional cohort study we used multiple datasets within SAIL; General Practice, Inpatient, Outpatient and Office of National Statistics to develop our case finding algorithm based on the coding nomenclatures and timing within these datasets. The results of this algorithm were then tested against two patient data sets: The UK MS Register (n=836), consisting of mostly self confirmed disease and a clinical cohort from South West Wales (n=713). Results From 4,757,428 records, the algorithm identified 6,194 cases of MS within Wales on 31st December 2020 (prevalence 221.65 [95%CI 216.17–227.24] per 100,000). Case finding sensitivity and specificity was 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% from the self-declared registry population. Conclusion We successfully identified MS cases within Wales and verified this within two independent data sets.

Published
2024
Full Text
View/download PDF

2. T cell composition and polygenic multiple sclerosis risk

Author

C.L. (Louk) de Mol, K.I.M. (Kirsten) Looman, M.M. (Marvin) van Luijn, K.L. (Karim) Kreft, P.R. (Philip) Jansen, MC van Zelm, J.J.F.M. (Joost) Smolders, T.J.H. (Tonya) White, H.A. (Henriette) Moll, R.F. (Rinze) Neuteboom, C.L. (Louk) de Mol, K.I.M. (Kirsten) Looman, M.M. (Marvin) van Luijn, K.L. (Karim) Kreft, P.R. (Philip) Jansen, MC van Zelm, J.J.F.M. (Joost) Smolders, T.J.H. (Tonya) White, H.A. (Henriette) Moll, and R.F. (Rinze) Neuteboom

Abstract

Background and purpose: Patients with multiple sclerosis (MS) have altered T cell function and composition. Common genetic risk variants for MS affect proteins that function in the immune system. It is currently unclear to what extent T cell composition is affected by genetic risk factors for MS, and how this may precede a possible disease onset. Here, we aim to assess whether an MS polygenic risk score (PRS) is associated with an altered T cell composition in a large cohort of children from the general population. Methods: We included genotyped participants from the population-based Generation R study in whom immunophenotyping of blood T cells was performed at the age of 6 years. Analyses of variance were used to determine the impact of MS-PRSs on total T cell numbers (n = 1261), CD4+ and CD8+ lineages, and subsets therein (n= 675). In addition, T-cell-specific PRSs were constructed based on functional pathway data. Results: The MS-PRS negatively correlated with CD8+ T cell frequencies (p = 2.92 × 10−3), which resulted in a positive association with CD4+/CD8+ T cell ratios (p = 8.27 × 10−9). These associations were mainly driven by two of 195 genome-wide significant MS risk variants: the main genetic risk variant for MS, HLA-DRB1*15:01 and an HLA-B risk variant. We observed no significant associations for the T-cell-specific PRSs. Conclusions: Our results suggest that MS-associated genetic variants affect T cell composition during childhood in the general population.

Published
2021
Full Text
View/download PDF

3. The autoimmunity-associated gene CLEC16A controls HLA-II expression by participating in the molecular machinery of late endosomal maturation (HUM2P.337)

Author

Jon Laman, Marvin van Luijn, Karim Kreft, Marlieke Jongsma, Steven Mes, Annet Wierenga-Wolf, Marjan van Meurs, Marie-Jose Melief, Rik van der Kant, Lennert Janssen, Hans Janssen, John Priatel, Rusung Tan, Jacques Neefjes, and Rogier Hintzen

Subjects
Immunology, Immunology and Allergy
Abstract

In GWA studies, CLEC16A has been identified as a risk gene for several major autoimmune diseases, including multiple sclerosis (MS). We show that CLEC16A is increased in MS and functionally links to HLA-II, and uncovered the molecular mechanism of CLEC16A as key regulator of HLA-II antigen presentation. We used the human melanoma cell line MelJuSo and primary moDC as APC models to silence CLEC16A with different siRNA and lentiviral shRNA. CLEC16A knockdown in MelJuSo cells and moDC resulted in cytoplasmic dispersion and strong accumulation of HLA-II+ late endosomes, suggesting impaired formation of multivesicular late endosomal compartments, i.e. MIIC. Indeed, in CLEC16A shRNA transductants, MIIC contained no or a few abnormally enlarged internal vesicles and showed an increased number of HLA-II molecules as compared to scrambled shRNA transductants of MelJuSo cells. CLEC16A associated with Rab7-interacting lysosomal protein (RILP) and the homotypic fusion and protein sorting (HOPS) complex, two members of the dynein motor complex regulating late endosomal trafficking and maturation. In addition, CLEC16A silencing disrupted RILP-mediated recruitment of HLA-II+ late endosomes to perinuclear regions. We reveal direct involvement of CLEC16A in the machinery regulating late endosomal processing of HLA-II. This novel C-type lectin function supports a pathogenic role of CLEC16A in autoimmune disease by promoting HLA-II antigen presentation via the formation of MIIC.

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results