Dataset Information

Multiple sclerosis risk variants influence the peripheral B-cell compartment early in life in the general population.

ABSTRACT:

Background and purpose

Multiple sclerosis (MS) is associated with abnormal B-cell function, and MS genetic risk alleles affect multiple genes that are expressed in B cells. However, how these genetic variants impact the B-cell compartment in early childhood is unclear. In the current study, we aim to assess whether polygenic risk scores (PRSs) for MS are associated with changes in the blood B-cell compartment in children from the general population.

Methods

Six-year-old children from the population-based Generation R Study were included. Genotype data were used to calculate MS-PRSs and B-cell subset-enriched MS-PRSs, established by designating risk loci based on expression and function. Analyses of variance were performed to examine the effect of MS-PRSs on total B-cell numbers (n = 1261) as well as naive and memory subsets (n = 675).

Results

After correction for multiple testing, no significant associations were observed between MS-PRSs and total B-cell numbers and frequencies of subsets therein. A naive B-cell-MS-PRS (n = 26 variants) was significantly associated with lower relative, but not absolute, naive B-cell numbers (p = 1.03 × 10^-4 and p = 0.82, respectively), and higher frequencies and absolute numbers of CD27⁺ memory B cells (p = 8.83 × 10^-4 and p = 4.89 × 10^-3 , respectively). These associations remained significant after adjustment for Epstein-Barr virus seropositivity and the HLA-DRB1*15:01 genotype.

Conclusions

The composition of the blood B-cell compartment is associated with specific naive B-cell-associated MS risk variants during childhood, possibly contributing to MS pathophysiology later in life. Cell subset-specific PRSs may offer a more sensitive tool to define the impact of genetic risk on the immune system in diseases such as MS.

SUBMITTER: de Mol CL

PROVIDER: S-EPMC10092523 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Multiple sclerosis risk variants influence the peripheral B-cell compartment early in life in the general population.

de Mol Casper L CL van Luijn Marvin M MM Kreft Karim L KL Looman Kirsten I M KIM van Zelm Menno C MC White Tonya T Moll Henriette A HA Smolders Joost J Neuteboom Rinze F RF

European journal of neurology 20221012 2

<h4>Background and purpose</h4>Multiple sclerosis (MS) is associated with abnormal B-cell function, and MS genetic risk alleles affect multiple genes that are expressed in B cells. However, how these genetic variants impact the B-cell compartment in early childhood is unclear. In the current study, we aim to assess whether polygenic risk scores (PRSs) for MS are associated with changes in the blood B-cell compartment in children from the general population.<h4>Methods</h4>Six-year-old children f ...[more]

PMID: 36169606

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Project description:BackgroundLow vitamin D and/or sun exposure have been associated with increased risk of multiple sclerosis (MS) onset. However, comparatively, few studies have prospectively examined associations between these factors and clinical course.ObjectivesTo evaluate the association of sun exposure parameters and vitamin D levels with conversion to MS and relapse risk in a prospectively monitored cohort of 145 participants followed after a first demyelinating event up to 5-year review (AusLong Study).MethodsSun exposure prior to and after onset measured by annual questionnaire; ultraviolet radiation (UVR) "load" estimated by location of residence over the life course and ambient UVR levels. Serum 25-hydroxyvitamin D [25(OH)D] concentrations measured at baseline, 2/3-year, and 5-year review. MS conversion and relapse assessed by neurologist assessment and medical record review.ResultsOver two-thirds (69%) of those followed to 5-year review (100/145) converted to MS, with a total of 252 relapses. Higher pre-MS onset sun exposure was associated with reduced risk of MS conversion, with internal consistency between measures and dose-response relationships. Analogous associations were also seen with risk of relapse, albeit less strong. No consistent associations were observed between postonset sun exposure and clinical course, however. Notably, those who increased their sun exposure during follow-up had significantly reduced hazards of MS conversion and relapse. Serum 25(OH)D levels and vitamin D supplementation were not associated with conversion to MS or relapse hazard.ConclusionWe found that preonset sun exposure was protective against subsequent conversion to MS and relapses. While consistent associations between postonset sun exposure or serum 25(OH)D level and clinical course were not evident, possibly masked by behavior change, those participants who markedly increased their sun exposure demonstrated a reduced MS conversion and relapse hazard, suggesting beneficial effects of sun exposure on clinical course.

Dataset Information

Multiple sclerosis risk variants influence the peripheral B-cell compartment early in life in the general population.

Background and purpose

Methods

Results

Conclusions

Publications

Multiple sclerosis risk variants influence the peripheral B-cell compartment early in life in the general population.

Similar Datasets

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