Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98105, USA.
Biomolecules. 2024 Jun 21;14(7):736. doi: 10.3390/biom14070736.
Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 gravida predominantly in <12-week gestation, we correlated the relative quantification of plasma proteins assessed via a multiplexed aptamer assay (SOMAScan) with AGP and CRP, quantified by immunoassay. We defined a plasma inflammasome as protein correlates meeting a false discovery rate <0.05. We examined potential pathways using principal component analysis. A total of 147 and 879 of 6431 detected plasma proteins correlated with AGP and CRP, respectively, of which 61 overlapped with both biomarkers. Positive correlates included serum amyloid, complement, interferon-induced, and immunoregulatory proteins. Negative correlates were micronutrient and lipid transporters and pregnancy-related anabolic proteins. The principal components (PCs) of AGP were dominated by negatively correlated anabolic proteins associated with gestational homeostasis, angiogenesis, and neurogenesis. The PCs of CRP were more diverse in function, reflecting cell surface and adhesion, embryogenic, and intracellular and extra-hepatic tissue leakage proteins. The plasma proteome of AGP or CRP reveals wide proteomic variation associated with early gestational inflammation, suggesting mechanisms and pathways that merit future research.
循环 α1-酸性糖蛋白(AGP)和 C 反应蛋白(CRP)常用于评估炎症,但这些生物标志物无法揭示炎症的复杂分子生物学。我们挖掘了母体血浆蛋白质组,以检测与 AGP 和 CRP 相关的蛋白质。在 435 名主要处于<12 周妊娠的孕妇中,我们通过多重适配体分析(SOMAScan)对血浆蛋白的相对定量进行了相关性分析,并用免疫分析法对 AGP 和 CRP 进行了定量。我们将与 AGP 和 CRP 相关的蛋白定义为具有<0.05 的错误发现率的蛋白。我们使用主成分分析来研究潜在的途径。在 6431 个检测到的血浆蛋白中,有 147 个和 879 个分别与 AGP 和 CRP 相关,其中 61 个与两种生物标志物都相关。阳性相关物包括血清淀粉样蛋白、补体、干扰素诱导和免疫调节蛋白。负相关物是微量营养素和脂质转运蛋白以及与妊娠相关的合成代谢蛋白。AGP 的主成分(PCs)主要由与妊娠稳态、血管生成和神经发生相关的负相关的合成代谢蛋白组成。CRP 的 PCs 在功能上更加多样化,反映了细胞表面和黏附、胚胎发生以及细胞内和肝外组织渗漏蛋白。AGP 或 CRP 的血浆蛋白质组揭示了与早期妊娠炎症相关的广泛蛋白质组学变异,这表明有必要对相关机制和途径进行进一步研究。