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Design of a targeted blood transcriptional panel for monitoring immunological changes accompanying pregnancy

Abstract:

Background: Immunomodulatory processes exert steering functions throughout pregnancy. Detecting diversions from this physiologic immune clock may help identify pregnant women at risk for pregnancy-associated complications. We present results from a data-driven selection process to develop a targeted panel of mRNAs that may prove effective in detecting pregnancies diverting from the norm.

Methods: Based on a de novo dataset from a resource-constrained setting and a dataset from a resource-rich area readily available in the public domain, whole blood gene expression profiles of uneventful pregnancies were captured at multiple time points during pregnancy. BloodGen3, a fixed blood transcriptional module repertoire, was employed to analyze and visualize gene expression patterns in the two datasets. Differentially expressed genes were identified by comparing their abundance to non-pregnant postpartum controls. The selection process for a targeted gene panel considered (i) transcript abundance in whole blood; (ii) degree of correlation with the BloodGen3 module; and (iii) pregnancy biology.

Results: We identified 176 transcripts that were complemented with eight housekeeping genes. Changes in transcript abundance were seen in the early stages of pregnancy and similar patterns were observed in both datasets. Functional gene annotation suggested significant changes in the lymphoid, prostaglandin and inflammation-associated compartments, when compared to the postpartum controls.

Conclusion: The gene panel presented here holds promise for the development of predictive, targeted, transcriptional profiling assays. Such assays might become useful for monitoring of pregnant women, specifically to detect potential adverse events early. Prospective validation of this targeted assay, in-depth investigation of functional annotations of differentially expressed genes, and assessment of common pregnancy-associated complications with the aim to identify these early in pregnancy to improve pregnancy outcomes are the next steps.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.3389/fimmu.2024.1319949

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Role:
Author
ORCID:
0000-0002-6368-6746
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Role:
Author
ORCID:
0000-0003-0912-1629
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Role:
Author
ORCID:
0000-0002-2301-2704


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Funder identifier:
https://ror.org/043z4tv69
Grant:
P50AR070594
U19 AI082715
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Funder identifier:
https://ror.org/006zn3t30
Grant:
R01 AR49772
R01 AR49772-07S2
R01 AR69572
AR43727
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Funder identifier:
https://ror.org/05wevan27
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Funder identifier:
https://ror.org/029chgv08
More from this funder
Funder identifier:
https://ror.org/01cawbq05


Publisher:
Frontiers Media
Journal:
Frontiers in Immunology More from this journal
Volume:
15
Article number:
1319949
Place of publication:
Switzerland
Publication date:
2024-01-30
Acceptance date:
2024-01-11
DOI:
EISSN:
1664-3224
ISSN:
1664-3224
Pmid:
38352867


Language:
English
Keywords:
Subtype:
Comment
Pubs id:
1687876
Local pid:
pubs:1687876
Deposit date:
2025-03-11
ARK identifier:

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