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Basic Science

Poster Session 1

(293) Cell-free RNA detection of "placental" and immunologic differentially-expressed genes in healthy pregnant vs. non-pregnant individuals

Tuesday, February 13, 2024

10:30 AM – 12:00 PM

Location: Prince George's Exhibit Hall CDE, Lower Atrium Level

Primary Author(s)

ND

Nathaniel Delaney-Busch, PhD

Mirvie, Inc.
South San Francisco, CA, United States

Coauthor(s)

AC

Alison Cowan, MD, MSCR

Dr.
Mirvie, Inc.
South San Francisco, CA, United States
CH

Carrie Haverty, MS

Mirvie, Inc.
South San Francisco, CA, United States
AK

Arkady Khodursky, PhD

Mirvie, Inc.
South San Francisco, CA, United States
MJ

Maneesh Jain, PhD

CEO
Mirvie, Inc.
South San Francisco, CA, United States
EN

Eugeni Namsaraev, PhD

Mirvie, Inc.
South San Francisco, CA, United States
IA

Ilma Abbas, BS

Mirvie, Inc.
South San Francisco, CA, United States
AM

Alison Moe, BS

Mirvie, Inc.
South San Francisco, CA, United States
KM

Kay Mekaru, BS

Mirvie, Inc.
South San Francisco, CA, United States
MR

Mitsu Reddy, PhD

Manager
Mirvie, Inc.
South San Francisco, CA, United States

Presenting Author(s)

Morten Rasmussen, MSc, PhD (he/him/his)

Head of Research
Mirvie, Inc.
South San Francisco, CA, United States

Objective: A healthy pregnancy requires extensive physiological adaptations systemically and locally at the maternal-fetal interface. An inability to test all tissues during a pregnancy limits understanding of the transcriptomic shifts that occur from the non-pregnant (NP) to pregnant state. Using cfRNA from maternal blood, we sought to reveal changes in global gene patterns in diverse NP and pregnant individuals.

Study Design:
For pregnant participants (N=231), individuals had a median age of 32 (range: 20-45) years, BMI of 24 (15 - 60), had no comorbidities and delivered at term without any known pregnancy complications. Maternal blood was drawn at 19 (18-22) weeks. NP individuals (N=49) were 32 (22-40) years, BMI 32 (19-61) and were collected by Discovery Life Sciences. All samples were collected and processed using the same protocol. Differentially expressed genes (DEG) were determined by spearman correlation and gene set overrepresentation by msigdbr v7.5.1.

Results: Pregnancy was associated with 7,301 DEG (adj p< 0.001), 38.5% of all plasma-detected genes. Top DEG are known pregnancy genes (top 3: CGA, CSH1, CSH2), with placental genes showing some of the largest differential expression, but 53 of 95 placental genes are also expressed in NP females, with 5 being significantly higher (fig1). Gene set analyses reveal overrepresentation of gene ontologies (GO) linked with immune genes, and even after excluding placental genes, the GO term for inflammatory response is the most overrepresented in pregnancy, demonstrating cfRNA can monitor immune modulation in addition to the fetal/placental genes.

Conclusion: Cell-free RNA demonstrates DEG between pregnant and NP individuals, providing insights into underlying biological changes. Placental genes are often expressed in NP females suggesting caution around analyses based on annotations. With several adverse pregnancy outcomes tied to immune response and the inflammatory response observed in these healthy pregnancies, cfRNA offers a comprehensive non-invasive approach to track physiologic changes, including immune response, in pregnancy.