Biology subjects

Engelfriet, P.

Publications and source records attributed to Engelfriet, P..

3 recordsLinked to original sources

bioRxiv2026

Longitudinal analysis of the B-cell receptor repertoire across 30 years of ageing

Background: The gradual decline in the functionality of the immune system during aging is commonly referred to as immunosenescence. This study aims to investigate changes in the B-cell receptor immunoglobulin heavy chain (BCR IGH) gene repertoire during natural aging and evaluate the dynamics of emergent low-level BCR IGH clonality in the elderly. We conduct a longitudinal study nested within the Doetinchem Cohort study, comprising 98 participants aged between 31 and 59 years old at study entry who had repeated blood samples drawn at 5 year intervals over a 30 year period (n=548 samples). We sequenced the IGH gene repertoire and evaluated the impact of aging on IGH gene repertoire clonality and diversity using linear mixed effects modeling. Results: Participants older than 60 years exhibited increased BCR IGH clonality and reduced IGH gene repertoire diversity. In a multivariable model, IGH gene repertoire diversity was significantly decreased for individuals with a dominant clonotype ratio greater than 10 (Beta=-0.57, p < 0.001). Additionally, a trend toward reduced IGH gene repertoire diversity was observed in participants aged 60-70 years (Beta =-0.19, p = 0.1) and those aged 70 years or older (Beta =-0.20, p = 0.13). IGH gene repertoire diversity was determined primarily by the naive and transitional B-cell pool, while BCR IGH clonality was influenced by switched memory and age-associated B-cell counts. Conclusions: In summary, our study indicates that IGH gene repertoire diversity decreases significantly after age 60, which coincides with an increased incidence of low-level BCR IGH clonality. This clonality may be driven largely by switched memory and age-associated B-cells. By providing deep insights into age-related dynamic changes in the IGH gene repertoire, these findings lay the groundwork for the molecular assessment and monitoring of incident clonality by clinicians and researchers alike.

immunology↗

bioRxiv2021

A new pipeline for the normalization and pooling of metabolomics data

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through PC-PR2 analysis; (iii) application of linear mixed models to remove unwanted variability, including samples originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.

bioinformatics↗

bioRxiv2021

Relation of inflammatory marker trajectories with frailty and aging in a 20-year longitudinal study

Little is known about the development of low-grade inflammation with age and its relationship with the onset of frailty. In this exploratory study, we investigated 18 inflammatory markers measured in blood of 144 individuals aged 65-75 years at study endpoint, collected over 20 years at five-year intervals. IFN{gamma}-induced markers and platelet activation markers changed in synchrony over time. Chronically elevated levels of IL-6-related markers, such as CRP and sIL-6R, were associated with frailty and becoming frail over time, poorer lung function, or less physical strength. Overweight was a possible driver of these associations. More and stronger associations were detected in women, such as between increasing sCD14 levels and frailty, indicating possible monocyte overactivation. Multivariate prediction of frailty showed low accuracy but confirmed the main results. In summary, we documented 20-year temporal changes of inflammatory markers in an aging population, and related these to clinically relevant health outcomes.

immunology↗