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4 results on '"C. Louk de Mol"'

1. Effector T Helper Cells Are Selectively Controlled During Pregnancy and Related to a Postpartum Relapse in Multiple Sclerosis

Author

Steven C. Koetzier, Rinze F. Neuteboom, Annet F. Wierenga-Wolf, Marie-José Melief, C. Louk de Mol, Angelique van Rijswijk, Willem A. Dik, Bieke Broux, Ronald van der Wal, Sjoerd A. A. van den Berg, Joost Smolders, and Marvin M. van Luijn

Subjects
relapse risk, third trimester, serum-related factors, hormones, inflammatory cytokine potential, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Multiple sclerosis (MS) patients are protected from relapses during pregnancy and have an increased relapse risk after delivery. It is unknown how pregnancy controls disease-contributing CD4+ T helper (Th) cells and whether this differs in MS patients who experience a postpartum relapse. Here, we studied the effector phenotype of Th cells in relation to pregnancy and postpartum relapse occurrence in MS.Methods: Memory skewing and activation of effector Th subsets were analyzed in paired third trimester and postpartum blood of 19 MS patients with and without a postpartum relapse and 12 healthy controls. Ex vivo results were associated with circulating levels of pregnancy-induced hormones and mirrored in vitro by exposing proliferating Th cells to corresponding serum samples.Results: Based on HSNE-guided analyses, we found that effector memory proportions of Th cells were increased in postpartum vs. third trimester samples from MS patients without a postpartum relapse. This was not seen for relapsing patients or healthy controls. CXCR3 was upregulated on postpartum memory Th cells, except for relapsing patients. These changes were verified by adding sera from the same individuals to proliferating Th cells, but did not associate with third trimester cortisol, estradiol or progesterone levels. For relapsing patients, activated memory Th cells of both third trimester and postpartum samples produced higher levels of pro-inflammatory cytokines.Conclusion: Effector Th cells are differentially regulated during pregnancy in MS patients, likely via serum-related factors beyond the studied hormones. The pro-inflammatory state of memory Th cells during pregnancy may predict a postpartum relapse.

Published
2021
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2. Response: No evidence for association between polygenic risk for multiple sclerosis and MRI phenotypes in approximately 30,000 healthy adult UK Biobank participants

Author

C Louk de Mol, Rinze F Neuteboom, Philip R Jansen, Tonya White, Human genetics, APH - Aging & Later Life, APH - Mental Health, Neurology, Erasmus MC other, and Child and Adolescent Psychiatry / Psychology

Subjects
Multiple Sclerosis, Phenotype, Neurology, Humans, Neurology (clinical), Magnetic Resonance Imaging, United Kingdom, Biological Specimen Banks, Genome-Wide Association Study
Published
2022

3. Polygenic Multiple Sclerosis Risk and Population-Based Childhood Brain Imaging

Author

Philip R. Jansen, R Q Hintzen, Tonya White, Meike W. Vernooij, Hieab H.H. Adams, Maria J. Knol, Vincent W. V. Jaddoe, Ryan L. Muetzel, Rinze F. Neuteboom, C. Louk de Mol, Human Genetics, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Neurology, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Epidemiology, Clinical Genetics, Erasmus MC other, Pediatrics, Human genetics, APH - Aging & Later Life, and APH - Mental Health

Subjects
0301 basic medicine, Oncology, Male, medicine.medical_specialty, Multifactorial Inheritance, Multiple Sclerosis, Genotype, Population, Neuroimaging, White matter, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Fractional anisotropy, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Brain/pathology, education, Child, Research Articles, education.field_of_study, business.industry, Multiple sclerosis, Genetic Predisposition to Disease/genetics, Brain, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Neurology, Multiple Sclerosis/genetics, Generation R, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Diffusion MRI, Research Article
Abstract

Objective: Multiple sclerosis (MS) is a neurological disease with a substantial genetic component and immune-mediated neurodegeneration. Patients with MS show structural brain differences relative to individuals without MS, including smaller regional volumes and alterations in white matter (WM) microstructure. Whether genetic risk for MS is associated with brain structure during early neurodevelopment remains unclear. In this study, we explore the association between MS polygenic risk scores (PRS) and brain imaging outcomes from a large, population-based pediatric sample to gain insight into the underlying neurobiology of MS. Methods: We included 8- to 12-year-old genotyped participants from the Generation R Study in whom T1-weighted volumetric (n = 1,136) and/or diffusion tensor imaging (n = 1,088) had been collected. PRS for MS were calculated based on a large genome-wide association study of MS (n = 41,505) and were regressed on regional volumes, global and tract-specific fractional anisotropy (FA), and global mean diffusivity using linear regression. Results: No associations were observed for the regional volumes. We observed a positive association between the MS PRS and global FA (β = 0.098, standard error [SE] = 0.030, p = 1.08 × 10 −3). Tract-specific analyses showed higher FA and lower radial diffusivity in several tracts. We replicated our findings in an independent sample of children (n = 186) who were scanned in an earlier phase (global FA; β = 0.189, SE = 0.072, p = 9.40 × 10 −3). Interpretation: This is the first study to show that greater genetic predisposition for MS is associated with higher global brain WM FA at an early age in the general population. Our results suggest a preadolescent time window within neurodevelopment in which MS risk variants act upon the brain. ANN NEUROL 2020;87:774–787.

Published
2020

4. Real-world validation of the 2017 McDonald criteria for pediatric MS

Author

Rogier Q. Hintzen, Immy A. Ketelslegers, Roos M van der Vuurst de Vries, E Daniëlle van Pelt, Rinze F. Neuteboom, C. Louk de Mol, Coriene E. Catsman-Berrevoets, Yu Yi M Wong, and Neurology

Subjects
Male, Pediatrics, medicine.medical_specialty, Validation study, Multiple Sclerosis, Adolescent, Encephalopathy, Diagnostic accuracy, Sensitivity and Specificity, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Child, business.industry, Infant, Reproducibility of Results, McDonald criteria, medicine.disease, Neurology, Child, Preschool, Acute disseminated encephalomyelitis, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract

ObjectiveTo compare the diagnostic accuracy of the McDonald 2017 vs the McDonald 2010 criteria to predict a second attack of MS (clinically definite MS [CDMS]) at the first attack of acquired demyelinating syndromes (ADS).MethodsOne hundred sixty-four children (aged ResultsAmong the 164 patients, 110 patients (67%) presented without encephalopathy (ADS–, female 63%; median age 14.8 years, IQR 11.3–16.1years) and 54 (33%) with encephalopathy (acute disseminated encephalomyelitis [ADEM], female 52%; median age 4.0 years, IQR 2.6–6.1 years). Of the 110 ADS– patients, 52 (47%) were diagnosed with CDMS within a median follow-up of 4.5 years (IQR 2.6–6.7 years). The sensitivity was higher for the 2017 criteria than for the 2010 criteria (83%; 95% CI 67–92, vs 49%; 95% CI 33–65; p < 0.001), but the specificity was lower (73%; 95% CI 59–84 vs 87%; 95% CI 74–94, p = 0.02). At baseline, 48 patients fulfilled the 2017 criteria compared with 27 patients when using the 2010 criteria. The results for children aged ConclusionsThe McDonald 2017 criteria are more sensitive than the McDonald 2010 criteria for predicting CDMS at baseline. These criteria can also be applied in children aged Classification of evidenceThis study provides Class II evidence that in children with ADS, the 2017 McDonald criteria are more sensitive but less specific than the 2010 McDonald criteria for predicting CDMS.

Published
2018

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