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2 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. 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

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