Hillegers, M. H. J. | Search bioRxiv

bioRxiv2024

Inflammatory markers in pregnancy - surprisingly stable. Mapping trajectories and drivers in four large cohorts.

Adaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. To translate findings from mechanistic preclinical studies to human pregnancies, studies of serum immune markers are the mainstay. The design and interpretation of human biomarker studies require additional insights in the trajectories and drivers of peripheral immune markers. The current study mapped maternal inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1{beta}, IL-6, IL-17A, IL-23, interferon-{gamma}) during pregnancy and investigated the impact of demographic, environmental and genetic drivers on maternal inflammatory marker levels in four multi-ethnic and socio-economically diverse population-based cohorts with more than 12,000 pregnant participants. Additionally, pregnancy inflammatory markers were compared to pre-pregnancy levels. Cytokines showed a high correlation with each other, but not with CRP. Inflammatory marker levels showed high variability between individuals, yet high concordance within an individual over time during and pre-pregnancy. Pre-pregnancy body mass index (BMI) explained more than 9.6% of the variance in CRP, but less than 1% of the variance in cytokines. The polygenic score of CRP was the best predictor of variance in CRP (>14.1%). Gestational age and previously identified inflammation drivers, including tobacco use and parity, explained less than 1% of variance in both cytokines and CRP. Our findings corroborate differential underlying regulatory mechanisms of CRP and cytokines and are suggestive of an individual inflammatory marker baseline which is, in part, genetically driven. While prior research has mainly focused on immune marker changes throughout pregnancy, our study suggests that this field could benefit from a focus on intra-individual factors, including metabolic and genetic components.

immunology↗

bioRxiv2018

Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders

Macroscale white matter pathways form the infrastructure for large-scale communication in the human brain, a prerequisite for healthy brain function. Conversely, disruptions in the brains connectivity architecture are thought to play an important role in a wide range of psychiatric and neurological brain disorders. Here we show that especially connections important for global communication and network integration are involved in a wide range of brain disorders. We report on a meta-analytic connectome study comprising in total 895 patients and 1,016 controls across twelve neurological and psychiatric disorders. We extracted disorder connectome fingerprints for each of these twelve disorders, which were then combined into a cross-disorder disconnectivity involvement map, representing the involvement of each brain pathway across brain disorders. Our findings show connections central to the brains infrastructure are disproportionally involved across a wide range of disorders. Connections critical for global network communication and integration display high disturbance across disorders, suggesting a general cross-disorder involvement and importance of these pathways in normal function. Taken together, our cross-disorder study suggests a convergence of disconnectivity across disorders to a partially shared disconnectivity substrate of central connections.

neuroscience↗