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Session: Nutritional Proteomics and Metabolomics (Oral 2)

(OR02-03-23) A Plasma Inflammasome in Early Pregnancy Among Rural Bangladeshi Women

Saturday, July 22, 2023
2:54 PM – 3:06 PM ET
Location:  Constitution B
Disclosure(s):
Hyunju Kim, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Jacquelyn R. Bedsaul, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Casey M. Rebholz, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly assessed inflammation biomarkers to aid interpretation of micronutrient status. However, they do not fully capture the complexity of inflammation, particularly in pregnancy—itself an inflammatory state. Using large-scale proteomics, we characterized the plasma inflammasome of AGP and CRP in early pregnancy in Bangladeshi women.

Methods: In 435 gravida ≤ 23 wk gestation, we correlated, by simple linear regression, relative plasma abundance of 6,431 proteins, quantified via a multiplexed aptamer assay (SomaLogic, Inc), with plasma levels of AGP and CRP quantified by immunoassay. Proteins associated with AGP and CRP at a false discovery rate (q) < 0.05 defined a plasma inflammasome. We used principal component analysis (PCA) to explore linear combinations of proteins that were significantly associated with AGP and CRP in linear regression in order to explain variances in distributions of AGP and CRP.

Results: 147 and 879 proteins correlated with AGP and CRP, respectively. Positive correlates included serum amyloid, complement, interferon-induced, and immune regulatory proteins. Micronutrient and lipid transporters, sex hormones, and pregnancy-related proteins were negatively correlated. PCA revealed the first two components explained 21.5% and 8.6% of variance in AGP, largely comprising pregnancy-related proteins (e.g., glypican-3, chorionic somatomammotropin hormone, and placenta growth factor) and proteins of angiogenesis, neurogenesis, and axon growth. The 3rd component members were low in complement proteins, but high in kallistatin (6.2% of variance explained), revealing well-known acute phase and anti-inflammatory proteins. The 1st and 2nd components explained 24.4% and 8.9%, respectively, of the variance in plasma CRP; the 1st dominated by cell surface and adhesion proteins and the 2nd by intracellular and extra-hepatic tissue leakage proteins. The 3rd component (5.4% of variance explained) was high in anabolic pregnancy-related proteins.

Conclusions: We identified proteomic biomarkers of early gestational, largely non-phlogistic inflammation. Proteins correlated with AGP and CRP had distinct patterns, with pregnancy more strongly influencing the AGP proteome.

Funding Sources: Johns Hopkins University